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Blood Transfusions, Blood Alternatives


and Transfusion Reactions
A Guide to Transfusion Medicine
Third Edition

JL Callum, Y Lin, PH Pinkerton


Sunnybrook Health Sciences Centre
K Karkouti, JM Pendergrast
University Health Network
N Robitaille
CHU Sainte-Justine
AT Tinmouth
The Ottawa Hospital
KE Webert
McMaster University Medical Centre

Published by
Preface to Third Edition
Since 2001 the Ontario Ministry of Health and Long-Term Care (MOHLTC)
has provided funding and oversight for a variety of initiatives directed at
promoting rational evidence-based use of blood components, derivatives
and alternatives, and reduction of transfusion errors. These initiatives have
included deploying 27 transfusion practitioners in 25 large hospitals that
together use a majority of blood products in the Province, supporting the
publication of this Guide to Transfusion Medicine and the development of
various allied online educational products for physicians, nurses, technologists
and patients. In 2007 the Provincial Blood Programs Coordinating Office
established the Ontario Regional Blood Coordinating Network (ORBCoN) to
promote measures for sound blood management; these include the updating
and publication of Bloody Easy and its on-line derivatives. Details of ORBCoN’s
mandate and activities can be found at www.transfusionontario.org

Copyright 2011, Ontario Regional Blood Coordinating Network CHANGES IN CONSUMPTION OF BLOOD COMPONENTS IN ONTARIO 2001-2010

All rights reserved. No part of this publication may be reproduced, stored Total Issues of Red Cells, Platelet and Frozen Plasma by CBS to Ontario Hospitals
Expressed as Units Per Thousand Population from 2000-2001 to 2009-2010
Consumption
in a retrieval system or transmitted in any form or by any means, electronic, 35 of labile blood
mechanical, photocopying, recording, or otherwise, without prior permission
components (red
in writing from the copyright owner. 30
cells, platelets and
25 frozen plasma) has
The content of this publication is that of the authors of the materials, papers,
shown a downward
publications, and proceedings. The editors and publishers do not assume any, 20
trend starting in
and disclaim all, liability for loss, injury, or damage arising from any use made
15 2007-2008 and
of any information, instructions, ideas, and recommendations therein.
accelerating in
10 2008-2009 and
First Edition, 2003.
2009-2010.
Second Edition, 2005 and 2006. 5

Third Edition, 2011.


0
2001 2002 2003 2004 2005 2006 2007 2008 2009 2010

Year Over Year Increments in Issues by CBS of Red Cells, Platelets and
Frozen Plasma to Ontario Hospitals Expressed as a Percentage Based on Consumption
Library and Archives Canada Cataloguing in Publication per 1000 population from 2001-2002 to 2009-2010
15

Bloody easy 3 : blood transfusions, blood alternatives and transfusion 10


reactions : a guide to transfusion medicine / J.L. Callum ... [et al.]. - 3rd ed.
5

Previously published: Bloody easy 2 / J.L. Callum. 0


Includes bibliographical references and index.
ISBN 978-0-9869176-0-8 -5

-10
1. Blood--Transfusion. I. Callum, J. L. (Jeannie), 1967- II. Ontario Regional
Blood Coordinating Network -15

RM171.C333 2011 615’.39 C2011-902555-8 -20


2002 2003 2004 2005 2006 2007 2008 2009 2010

2 3
T H E 1 0 C O M M A N D M E N T S

Adapted from the WHO 1998 recommendations for the Important Notes
clinical use of blood: 1
◆ This booklet is an educational tool to assist in
providing care to patients.
1. Transfusion is only one part of patient management. ◆ The recommendations do not replace the need
2. Prescribing decisions should be based on national to consult an expert in transfusion medicine.
guidelines on the clinical use of blood, taking into
account the needs of each individual patient. ◆ These recommendations should not be applied
rigidly, since they could result in some patients
3. Blood loss should be minimized (and blood receiving unnecessary transfusions or experiencing
conservation strategies considered*) to reduce adverse effects from under-transfusion.
a patient’s need for transfusion.
4. A patient with acute blood loss should receive
effective resuscitation (IV replacement fluids,
Disclaimer: While the advice and information in these guidelines are
oxygen, etc.) while assessing the need for transfusion. believed to be true and accurate at the time of publishing, neither the
5. A patient’s hemoglobin value, although important, authors nor the publishers accept any legal responsibility or liability for
should not be the sole deciding factor in starting any errors or omissions in the information provided, or for any of the
transfusion of red cells. The decision to transfuse recommendations made. Any decision involving patient care must be
should be supported by the need to relieve clinical based on the judgement of the attending physician according to the
signs and symptoms and to prevent morbidity and needs and condition of each individual patient.
mortality.
6. The clinician should be aware of the risks of
transfusion-transmissible infection (and non-
infectious risks*) in the blood and blood products
that are available for each individual patient.
7. Transfusion should be prescribed for a patient
ONLY when the benefits outweigh the risks.
8. The clinician should clearly record the reason
for the transfusion.
9. A trained health care professional should monitor
the transfused patient and respond immediately
if any adverse effects occur.
10. Informed consent for transfusion should be
obtained prior to transfusion.*

* Additional recommendations by the Blood Products Advisory


Panel for the 1st and 2nd Editions (see Appendix C, page 138).

4 5
C O N T E N T S

Acknowledgements 1 Transfusion Basics . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 8–13


Special thanks to the following people and 2 Red Blood Cell Basics . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 14–21
organizations who contributed specific knowledge,
expertise, or materials to this Bloody Easy Guide 3 Components . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 22–33
and the associated e-learning program: • Platelets . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 22
• Frozen Plasma . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 28
Mr. Zenon Bodnaruk • Cryoprecipitate . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 32

Mr. Keith Buchanan 4 Risk Charts . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 34–37


◆ Physician risk chart . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 34
Dr. Lisa Burry ◆ Patient risk chart . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 36

Dr. Rob Cartotto 5 Transfusion Reactions . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 38–73


◆ Reporting . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 38
Dr. Allison Collins ◆ Reaction by symptom . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 39
• Fever . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 40
Mr. Ahmed Coovadia • Dyspnea . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 47
• Urticaria & Other Allergic Reactions/Anaphylaxis . . . . . . . . . . . . . 54
Ms. Stephanie Cope
• Hypotension . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 58
CSL Behring • Hemolysis after transfusion . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 60
• Cytopenias after transfusion . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 62
Dr. Gilles Delage • Virus, Parasite and Prion Infections . . . . . . . . . . . . . . . . . . . . . . . . 66
• Complications of massive transfusion . . . . . . . . . . . . . . . . . . . . . . . 70
Dr. Margaret Fearon
6 Blood Conservation . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 74–91
Dr. David Good ◆ Good surgical technique . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 76
◆ Iron . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 78
Dr. Barbara Hannach ◆ Preoperative Autologous Blood Donation (PAD) . . . . . . . . . . . . . . . . 80
◆ Acute Normovolemic Hemodilution (ANH) . . . . . . . . . . . . . . . . . . . . . 83
Mr. David Howe ◆ Intraoperative Cell Salvage . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 84
Dr. Heather Hume
◆ Erythropoietin in elective surgery . . . . . . . . . . . . . . . . . . . . . . . . . . . . 86
◆ Antifibrinolytics . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 88
Dr. Marianne Lavoie ◆ DDAVP . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 90
◆ Regional Anesthesia . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 90
Ms. Helen Meaney ◆ Topical Agents . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 90
◆ Other blood conservation strategies . . . . . . . . . . . . . . . . . . . . . . . . . . 91
Ms. Lisa Merkley
7 Erythropoietin and Medical Patients . . . . . . . . . . . . . . . . . . 92–95
Octapharma ◆ Chronic Renal Failure (CRF) . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 92
◆ Anemia associated with malignancy . . . . . . . . . . . . . . . . . . . . . . . . . . 94
Dr. Robert Skeate ◆ HIV Infections . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 95
Talecris 8 Fractionated Blood Products . . . . . . . . . . . . . . . . . . . . . . . . 96–121
Dr. Richard Wells 9 Sickle Cell Disease . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 122–135
10 Appendices . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 136–153
◆ Appendix A: Price list . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 136
◆ Appendix B: Patients who are Jehovah’s Witnesses . . . . . . . . . . . . . 137
◆ Appendix C: Original Advisory Panels for Bloody Easy, Version 1 . . 138
◆ References . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 140

6 7
Transfusion Basics
T R A N S F U S I O N B A S I C S

A Overview

Who regulates Donor screening


■ Health Canada regulates blood collection, ■ Donors screened using:
testing, processing, and distribution. ◆ donor questionnaire

■ The agency has published standards ◆ donor vital signs (temperature, heart rate,
relating to hospital transfusion practices. blood pressure)
◆ The second edition of these standards is ◆ donor hemoglobin
available from the Canadian Standards ■ Donor units tested for:
Association (Can/CSA-Z902-10).
DONOR UNITS SPECIFIC AGENTS TESTS USED
TESTED FOR:

Red Blood
Cell Basics
National Standard Blood groups ABO and Rhesus (Rh) D Blood group serology
■ Canadian Society for Transfusion Red cell alloantibodies
Medicine – Standards for Hospital
Viruses HIV 1 and 2 Antibody and nucleic acid testing
Transfusion Services Version 3, Hepatitis B Surface antigen, core antibody
February 2011 www.transfusion.ca. and nucleic acid testing
Hepatitis C Antibody and nucleic acid testing
HTLV I and II Antibody
Who collects West Nile Virus Nucleic acid testing
■ Canadian Blood Services (CBS),
in all provinces and territories Bacteria Syphilis Serology
except Québec. Bacterial contamination Bacterial culture
(Platelets only)
Héma-Québec (HQ) in Québec.

Components

Parasites Chagas Disease Antibody
(at risk donors only)

■ All donors are unpaid volunteer donors.


■ Plasma for fractionation is screened for
parvovirus B19 by nucleic acid testing.

8 9
Transfusion Basics
T R A N S F U S I O N B A S I C S

Whole blood processing Process for Preparing Blood Components from Donated Units
■ Collect 500 mL whole blood. 350 mL Step 1 - Whole Blood Separation
■ Divert the first 40 mL to reduce risk of
bacterial contamination from donor skin; Plasma Plasma

the 40 mL are used for donor unit testing.


■ Blood is centrifuged and separated into Buffy
Buffy Coat
3 parts: cent
rifuged @ 20°C
Coat

◆ Red Blood Cells

◆ Plasma
RBC RBC

◆ Buffy coat

■ The Buffy coat units from four donors Step 2 - RBC Additive
are combined with one plasma unit and

Red Blood
Cell Basics
further processed to separate the platelets.
■ The red blood cell and platelet components
HQ provides
are leukoreduced. RBC
buffy coat RBC &
Leukoreduced
■ Certain groups of patients need irradiated platelets from Additive
RBC

blood components to prevent transfusion- 5 units of Leukoreduction


associated graft vs host disease (TA-GvHD). buffy coat.
■ CBS and HQ provide irradiated products on
demand. Step 3 - Plasma
◆ Refer to TA-GvHD (page 63) for list of Female
Fractionation to manufacture albumin and IVIG
Plasma
patient groups that need irradiated blood
Plasma For Transfusion

Components
Plasma
B Red Blood Cells and Components: Male
Cryo-
Plasma
Storage Conditions and Volumes super-
natant

COMPONENT VOLUME STORAGE LIMIT STORAGE TEMP. Plasma


Frozen at - 18°C
Red blood cells 280 mL 42 days 1-6°C Cryo-
precipi-
Buffy coat derived platelets 350 mL 5 days 20-24°C tate
(from 4 units)

Apheresis platelets 300 mL 5 days 20-24°C Step 4 - Buffy Coat Platelet

Frozen plasma 250 mL 1 year -18°C or colder


Male
Plasma
Apheresis plasma 500 mL 1 year -18°C or colder
Cryoprecipitate 15 mL 1 year -18°C or colder 4 Platelet
Buffy Coats
Autologous red blood cells 280 mL 42 days 1-6°C
Autologous frozen plasma* 250 mL 1 year -18°C or colder Leuko-
reduced
Pool
Directed red blood cells 280 mL 42 days 1-6°C Buffy Coat
Platelets
Directed frozen plasma* 250 mL 1 year -18°C or colder
Leukoreduction
* Only on request and referral by patient’s physician.

10 11
Transfusion Basics
T R A N S F U S I O N B A S I C S

C Informed Consent D Directed Blood Donations

When What
■ Discuss the option of a transfusion early ■ Directed blood donations are units donated
enough to allow for a blood alternative(s) for a specific transfusion recipient.
to be considered.
Who
What 2 ■ Currently in Canada (other than Québec),
■ Include in your discussion: directed blood donations are available

!
A T T E N T I O N
◆ Description of blood or blood product only for the following recipients:
Refer to pages 34-36 for risk ◆ To minor child from parent
◆ Benefits
charts, to assist discussion
◆ Risks ◆ Patients with rare red blood cell types

Red Blood
Cell Basics
of risks with patients.
◆ Alternatives ◆ HLA-alloimmunized, thrombocytopenic

■ Give your patient the opportunity to ask patients requiring HLA-matched platelet
questions. transfusions
◆ Infants with neonatal allo-immune

Of note thrombocytopenia
■ Confirm that you discussed consent ■ In Québec, all recipients may have
with the patient, by noting it in the access to directed blood donations,
patient’s chart. on recommendation of their physician.
■ Complete the informed consent
documentation as required at your Where
hospital. ■ Directed blood donations are collected

Components
■ If transfusion is required, clearly by CBS and HQ.
document the reason in the patient’s
Of note
chart.
■ Directed blood donations transfused to
■ In the special case of Jehovah’s Witnesses, family members must be irradiated to
helpful advice may be obtained from prevent TA-GvHD.
their Hospital Information Services
■ Presently, there are no data to support
24 hours a day at 1-800-265-0327
the concept that directed donors are
(see Appendix B, page 137).
safer than volunteer donors.
■ Directed blood donation programs are
Pediatrics logistically complicated to administer and
financially more expensive than volunteer
■ For minors, the parent or
donor programs.
legal guardian must give
informed consent.
■ Teenagers should give informed
consent themselves. The age at
which teenagers can give informed
consent varies from province to
province. Refer to provincial
legislation.

12 13
Transfusion Basics
R E D B L O O D C E L L B A S I C S

A When and How to Order Tests B Routine Transfusion Medicine Tests


TEST TIME (MIN) INFORMATION
A T T E N T I O N
1. Transfusion MIGHT 1. Transfusion

!
ABO group 5 Patient RBCs tested for A and B antigen.
occur during PLANNED Uncrossmatched blood is
admission rarely required; consider Rh (D) group 5 Patient RBCs tested for D antigen.
2. Surgery with if clinical status precludes
2. Surgery with > 10% risk of waiting for antibody Antibody 45 Screens for RBC alloantibodies formed as
< 10% risk of transfusion screen and crossmatch Screen a result of prior transfusion or pregnancy.
transfusion (most (45 mins).
minor surgeries do Antiglobulin 45 Mandatory for patients with RBC
NOT require even Crossmatch alloantibodies. Involves incubation of donor
a group or screen) RBCs, recipient plasma/serum, and anti-IgG.

Red Blood
Cell Basics
Immediate 5 Testing involves mixing of donor RBCs and
Spin recipient plasma/serum. Used to verify ABO
Group & Screen Group & Screen & Crossmatch compatibility only.
Crossmatch
Computer 2 Computer selects appropriate unit (donor units
GROUP
Crossmatch must have been re-tested to confirm ABO group
and recipient sample must be tested twice).
ABO group
Note: For centres using immediate spin or computer crossmatch, crossmatching red
Rh (D) group cell units in advance of transfusion/surgery is rarely required unless antibody screen
is positive.
SCREEN

Checking Identity of Patient

Components
Antibody Screen C

CROSSMATCH You must accurately identify the


patient at the following times:
Antiglobulin Crossmatch OR 1. When collecting a blood sample
◆ Accurately label each specimen
Immediate Spin Crossmatch OR
before leaving the patient’s bedside.
Computer Crossmatch
2. Before beginning the transfusion
◆ Verify the patient’s identity, by

checking the name and date of


Pediatrics birth on their wristband against the
■ For infants less than 4 months of age, initial testing must identification on the blood component
include ABO and Rh (D) group and an antibody screen, label before transfusing, and, where
using either a sample from the infant or mother. possible, also by verbal confirmation.
■ If an unexpected RBC alloantibody is detected in the infant’s or
mother’s specimen, it is required that the infant receive RBC units A T T E N T I O N

!
lacking the corresponding antigen(s) or units compatible by Check the patient’s wristband
antiglobulin crossmatch. before transfusing!
■ This regimen should continue until the maternal antibody is no Failure to check is the major
longer detected in the infant’s sample. cause of acute hemolytic
transfusion reactions.

14 15
Transfusion Basics
R E D B L O O D C E L L B A S I C S

D Monitoring & Infusion Practices

!
How Transfuse
■ RBCs must be transfused through a blood ■ In non-urgent/non-bleeding/inpatient A T T E N T I O N
administration filter (170-260 microns). settings red blood cells should be Transfuse one
■ RBCs are compatible ONLY with normal transfused during daytime hours unit at a time.
saline. (for patient safety) and transfused
■ 16-18 gauge needle required for fast flow one unit at a time.

!
rates. ■ Assess patient prior to ordering
■ 20-22 gauge needle appropriate for patients another unit. A T T E N T I O N
with small veins. ■ Each unit is usually infused over Infuse each unit over
2 hours, but always within 4 hours

Red Blood
2 hours, maximum 4 hours.

Cell Basics
When of issue from blood bank.
■ Start within 30 minutes of removing RBCs ■ Consider a slower rate for patients
from refrigeration. at risk of circulatory overload.
■ In massive transfusion, blood should
Storage only be warmed using an approved
■ Only store RBCs in a temperature-controlled blood warming device.
refrigerator with continuous temperature
monitoring by the transfusion service.
■ Freezing or heating blood may cause
hemolysis, and may harm the patient.
E Ordering RBCs

!
Monitor patient If the patient is not adequately volume

Components
■ A T T E N T I O N
■ Check patient’s vital signs; vital signs resuscitated, the hemoglobin value may Record the order in the
should be assessed: be spuriously high OR, in the setting correct patient’s chart.
◆ prior to starting of over hydration, spuriously low.
◆ 15 minutes after starting ■ A falsely low hemoglobin value may
◆ at end of transfusion result if test samples are taken near
a site of IV infusion.
◆ during any transfusion reactions.
■ Certain patients require irradiated or
■ Transfuse slowly (50 mL/hr) for the
CMV-seronegative products. Refer
first 15 minutes, where appropriate.
to page 63 (irradiated products) and

!
■ Monitor the patient closely for the first page 67 (CMV-seronegative products).
15 minutes. A T T E N T I O N
Monitor patient closely
for first 15 minutes. Pediatrics
Pediatrics 3,4
For pediatric patients, transfuse Dosage:
slowly (1 ml/kg/h, up to 50 ml) ■ A transfusion of 15 ml/kg
for the first 15 minutes. Usual of RBC stored in an additive
administration rate is 5 ml/kg/h, solution is expected to raise
up to 150 ml/h. the hemoglobin level by
approximately 20 g/L.5

16 17
Transfusion Basics
R E D B L O O D C E L L B A S I C S

F Indications for RBCs

Acute blood loss ACUTE BLOOD LOSS & ■ Recombinant erythropoietin does not reduce
ANEMIA IN CRITICAL CARE
■ Maintain hemoglobin > 70 g/L during RBC transfusion requirements in critically ill
active bleeding.6 patients and its use is associated with an
◆ Consider rate of bleeding, hemodynamic increased rate of thrombotic events.12
factors, evidence of tissue ischemia,
institutional speed of blood delivery/
laboratory testing in decision about
transfusion. Pediatrics
◆ Ensure prompt blood availability when
Anemia in pediatric critical care
■ In children whose condition is
hemoglobin is < 80 g/L

Red Blood
Cell Basics
stable in the ICU, a transfusion
■ Consider maintaining a higher hemoglobin
is not usually required unless
level for patients with:7
the patient’s hemoglobin is
◆ Impaired pulmonary function
less than 70 g/L.
◆ Increased oxygen consumption (fever, chills)
■ A restrictive transfusion strategy
◆ Unstable or acute coronary syndromes 8,9,10 (trigger Hb 70 g/L) was proven to
◆ Coronary artery disease9 be as safe as a liberal transfusion
◆ Uncontrolled/unpredictable bleeding.
strategy (95 g/L).11
◆ This recommendation may not be
■ Consider that patients with hemoglobin
>100 g/L are unlikely to benefit from applicable to neonates under 28 days
transfusion. old, children with severe hypoxemia,
hemodynamic instability, active blood

Components
Anemia in critical care and coronary care loss or cyanotic heart disease as these
■ Recommend a transfusion when the patient’s groups were excluded from this clinical
hemoglobin is less than 70 g/L.9 trial.
■ In a patient with an acute coronary syndrome, Anemia in neonatal critical care
there is controversy over where to maintain ■ Several guidelines for small-volume RBC
the hemoglobin level.8,9,10 transfusions for newborns have been
◆ There are insufficient data to recommend published in the last decade.13,14,15,16
maintaining the hemoglobin above some ■ Two recent randomized controlled trials
arbitrary level came to differing conclusions regarding
◆ Consider transfusing if there are clear signs whether a restrictive strategy was as
of inadequate tissue oxygen delivery in a safe as a liberal strategy.17,18
patient with a low hemoglobin and an ■ Attention must be drawn to
acute coronary syndrome phlebotomy for laboratory testing

!
■ Unnecessary phlebotomy for laboratory A T T E N T I O N since it is a significant cause of anemia
testing is a major contributor to anemia in neonates.19
Minimize blood work as
in a critically ill patient. ■ Due to the conflicting evidence from
it contributes to need for
■ Except for patients with unstable coronary transfusion in critical care. randomized control trials in this patient
artery syndromes, a restrictive transfusion population, an accepted standard
policy (trigger Hb 70 g/L) has proved at approach for the transfusion of
least as effective as a liberal transfusion neonates cannot be recommended.
policy for critically ill patients.9,11

18 19
Transfusion Basics
R E D B L O O D C E L L B A S I C S

Perioperative patients Chronic anemia 23,24


■ Manage patients undergoing elective ■ Administer transfusions only when
surgery preoperatively, intraoperatively, and alternatives do not exist or have failed.6
postoperatively with strategies to minimize

!
■ Administer RBCs at intervals to maintain
the need for RBCs.6 (see pages 74-75)
A T T E N T I O N the hemoglobin just above the lowest
■ Administer RBCs one unit at a time in concentration that is not associated with
non-urgent settings.7,20 RBCs:
symptoms of anemia.6
One unit at a time.
■ Assess patient prior to transfusing additional ■ Assess patients that are expected to have
units (clinical exam and hemoglobin level).7 long-term transfusion dependent survival
■ For orthopedic patients with cardiovascular for iron overload.

Red Blood
Cell Basics
disease, post operative transfusion for ■ Chelation therapy should be considered
symptomatic anemia or hemoglobin of less in patients who are iron-overloaded,
than 80 g/L does not increase adverse transfusion dependent, and who have
outcomes or delay recovery compared to a a life expectancy of more than one year.
transfusion trigger of 100 g/L.21 ■ Iron overload is typically present after
■ Follow guidelines for perioperative patient:7 20 units of RBCs (patients with a significant
component of ineffective erythropoiesis
HEMOGLOBIN RECOMMENDATION
and upregulation of iron absorption may
> 100 g/L Likely inappropriate except in exceptional circumstances become iron overloaded more quickly).
■ Monitor serum ferritin and transferrin
70-100 g/L Likely to be appropriate if there are signs or symptoms saturation: tissue iron overload is likely

Components
of impaired oxygen delivery if ferritin > 1000 ug/L and transferrin
saturation > 75%.
< 70 g/L Likely to be appropriate ■ Either desferrioxamine or deferasirox
< 60 g/L are appropriate as first line therapy, with
Transfusion highly recommended22
target ferritin between 500 and 1000 ug/L,
◆ Young patients with low risk of ischemic cardiovascular
and appropriate monitoring for drug
disease can sometimes tolerate greater degrees of anemia
toxicity (including annual eye and ocular
examinations).

20 21
Transfusion Basics
C O M P O N E N T S : Platelets

A Basics

■ Platelets come in 3 forms: What


◆ Pool of 4 units of buffy coat derived ■ ABO/Rh-identical platelets are
platelets (pools of 5 in Québec) preferred, but ABO/Rh non-identical
◆ Single donor (collected by apheresis) platelets may be transfused when
◆ HLA-matched single donor (for patients
ABO/Rh-identical platelets are not
available.
with HLA-alloimmunization and refractory
to random donor platelets) ■ Rh negative women of childbearing
potential require Rh-immunoglobulin
■ In non-bleeding patients, the risk of
when Rh positive platelets are
spontaneous hemorrhage is low when
transfused to avoid formation of
platelet count is greater than 10 x 109/L.

Red Blood
Cell Basics
anti-D antibody.
■ In Canada, all platelet products are tested ◆ Each platelet pool contains up to
for bacterial contamination which lowers
0.5 mL of red cells26
but does not eliminate the risk of sepsis.
◆ Each 120 ug of Rh-immunoglobulin
■ The commonly held belief that platelet
covers 12 mL whole blood (6 mL
transfusions are contraindicated in immune
RBC) and lasts approximately 21 days
mediated thrombocytopenia (i.e., HIT, ITP,
PTP) is not supported by substantial

!
evidence.25
Storage A T T E N T I O N
■ Platelets must be stored at 20-24˚C
Do NOT put platelets
(room temperature) with constant
B Monitoring & Infusion Practices in the refrigerator.

Components
INFUSION mixing to preserve platelet function.
■ Do not refrigerate. Inadvertently
How “chilled” platelets will be rapidly
■ Buffy coat derived pooled platelets from cleared by hepatic macrophages.
multiple donors or single donor apheresis
platelets are supplied.
■ Platelets must be transfused through Pediatrics
a blood administration filter (170-260 Dose: 13,14
microns). ■ Children over 10 kg:
■ Fresh blood administration filter preferred. 1 U/10kg, up to an equivalent
■ Platelets are compatible ONLY with normal of 1 pool of platelets OR
saline. 10 ml/kg up to a maximum
of 1 pool of platelets.
■ Neonates 10 ml/kg

22 23
Transfusion Basics
C O M P O N E N T S : Platelets

B Monitoring & Infusion Practices (cont’d) PLATELET REFRACTORINESS MANAGEMENT ALGORITHM27,29

Post-transfusion increment in platelet count < 7.5 x 109/L


Monitor patient
■ Check patient’s vital signs; vital signs should
be assessed prior to starting, 15 minutes No Yes
after starting, at end of the transfusion
and if there are any transfusion reactions.
■ Transfuse slowly (50 mL/hr) for the first Refractoriness not present Use ABO identical platelets
15 minutes, where possible.
■ Monitor the patient closely for the first Continue use of pooled Platelet count increment
15 minutes. donor platelets < 7.5 x 109/L
■ Each dose of platelets should increase

Red Blood
Cell Basics
!
the patient’s platelet count at 1 hour
by at least 15-25 x 109/L.27 A T T E N T I O N Monitor post-transfusion
platelet count Yes No
Monitor patient closely
for first 15 minutes.
Transfuse
■ Recommended infusion time is 60 minutes Consider, and where present, manage
per dose (maximum infusion time 4 hours). other causes of refractoriness.
If absent, test for HLA antibodies

Follow-up
Antibodies present
■ Obtain post-transfusion platelet counts

Components
(10-60 min.) after all transfusions to ensure
adequate replacement and recognition of Yes No
platelet refractoriness.28
◆ A platelet increment of < 7.5 x 109/L

suggest refractoriness and requires Determine Continued poor


investigation.27 patient’s responses
■ If increments in platelet count are NOT HLA type
adequate, special measures are required.
Refer to the algorithm on page 25.
Select HLA- Yes No
compatible
apheresis donor
and supply single
donor irradiated
platelets

Post-transfusion Seek transfusion


increment in medicine
platelet count consultation*
> 7.5 x 109/L
* Consult Blood Centre physician
where no hospital transfusion
medicine physician available. Yes No
24 25
Transfusion Basics
C O M P O N E N T S : Platelets

C Indications & Infusion Recommendations

Pediatrics – Neonates 13
PLT (x 109/L) CLINICAL SETTING SUGGEST PLT (x 109/L) CLINICAL SETTING SUGGEST

< 10 Non-immune Transfuse 1 pool < 30 Any neonate 10 ml/kg


thrombocytopenia of platelets28
< 50 Stable premature neonate 10 ml/kg
< 10 Non-immune thrombocytopenia Transfuse 1 unit of with active bleeding or
& HLA-alloimmunized HLA-matched apheresis planned invasive procedure
platelets28 < 100 Sick preterm neonate with 10 ml/kg
active bleeding, planned

Red Blood
Cell Basics
< 20 Non-immune thrombocytopenia Transfuse 1 pool
and fever > 38.5˚C or coagulopathy of platelets28 invasive procedure, or DIC

< 20 Procedures not associated with Transfuse 1 pool Note: These guidelines are based on experts opinions and are not evidence
significant blood loss of platelets28 driven since there are no clinical trials in this patient population.

20-50 Procedures not associated with 1 pool of platelets on


significant blood loss hold, transfuse only if
significant bleeding22

< 50 Epidural anesthesia and lumbar Transfuse 1 pool


puncture immediately before
procedure 30

Components
< 50 Procedures associated with Transfuse 1 pool
blood loss or major surgery immediately before
(> 500 ml expected blood loss) procedure 22,31

< 50 Immune thrombocytopenia Transfuse platelets only


with serious bleeding32

< 100 Pre-neurosurgery or head trauma Transfuse 1 pool


of platelets33,34

Any Platelet dysfunction and marked Transfuse 1 pool


bleeding (e.g., post cardiopulmonary of platelets22
bypass, aspirin, antiplatelet agents)

26 27
Transfusion Basics
C O M P O N E N T S : FP rl a
o tzeelne tPs l a s m a 3,9

A Basics35,36 B Monitoring & Infusion Practices

■ Frozen plasma (FP) can be derived from How


two sources: ■ Frozen plasma must be transfused
◆ Random donor plasma (250 mL) through a blood administration filter
◆ Apheresis donors (250 or 500 mL) (170-260 microns).
• plasma collected alone or in conjunction ■ FP is compatible ONLY with normal
with platelets saline.
• large apheresis units (500 mL) are equivalent Dose
to 2 units of random donor plasma ■ Small adult: 3 units (10-15 mL/kg).37
■ Large adult: 4 units (10-15 mL/kg).37

Red Blood
Cell Basics
■ Pediatric: 10 to 20 mL/kg.

When
■ The recommended infusion time is 30
to 120 minutes (maximum time 4 hours).

Storage
■ Frozen plasma is kept frozen for up to
one year.
■ After issue, FP and FFPA should be

!
administered within 4 hours.
◆ The biological half-life of plasma
A T T E N T I O N

Components
coagulation proteins is different The effective half-life of FP
for each protein:38 is measured in hours.
• 3-6 hours for factor VII Administer immediately
• 8-12 hours for factor VIII before planned procedures.
Notes: • 2-3 days for factors II and IX
■ ‘Frozen plasma’ (FP) is frozen within
24 hours of collection and ‘Apheresis Fresh Monitor patient
Frozen Plasma’ (FFPA) is frozen within ■ Check patient’s vital signs; vital signs
8 hours. should be assessed prior to starting,
15 minutes after starting, at end of
■ FP is produced from whole blood donations
transfusion and if there are any
with longer “hold” as part of the buffy-coat
transfusion reactions.
production method.
■ Transfuse slowly (50 mL/hr) for the
■ The factor VIII is slightly lower in FP but
first 15 minutes, where possible.
this is not clinically significant. All other
coagulation factor levels are the same ■ Monitor the patient closely for the
in FP and FFPA, and the 2 products can first 15 minutes.

!
be used interchangeably. ■ If clinically indicated, the PT/INR and
■ FP and FFPA contain 400-900 mg fibrinogen PTT should be checked after infusion A T T E N T I O N

per 250 mL equivalent (4 units of FP contain (10-60 minutes). Monitor patient closely
approximately 2.5 g of fibrinogen). for first 15 minutes.

28 29
Transfusion Basics
C O M P O N E N T S : FP rl a
o tzeelne tPs l a s m a 3,22

C Indications for Frozen Plasma

1. Bleeding or prior to an operative procedure A T T E N T I O N 2. Microvascular bleeding or massive A T T E N T I O N

!
in patients with INR, PT or PTT more than FP is NOT indicated or transfusion AND patient’s clinical 1:1 replacement with FP

!
1.5 times normal when no coagulation factor required when INR < 1.5 status precludes waiting 30-45 and RBCs not required
concentrates or other alternative therapy as coagulation factor minutes for INR/PT/PTT results.2 when patient is expected
are available.2 levels are adequate for to need less than 10 PRBC
◆ Repeating INR/PT/PTT after infusion hemostasis. 3. Thrombotic thrombocytopenic units over 24 hours or
of FP may be beneficial to ensure purpura. time allows replacement
that replacement is adequate33 based on laboratory
testing.

!
Note: 39,40,41,42
A T T E N T I O N

Red Blood
Cell Basics
■ If available, prothrombin complex
concentrates (PCCs) should be used for IV Vitamin K works
urgent reversal of warfarin therapy or faster than oral.
treatment of vitamin K deficiency in a
bleeding patient OR a patient requiring an
emergency invasive procedure. Vitamin K
A T T E N T I O N
(2-10 mg i.v.) should also be given.

!
■ For non-emergent reversal of warfarin or
FP is NOT indicated or
effective for reversal of
vitamin K deficiency, vitamin K should be
heparin, low molecular
used rather than PCCs. weight heparin,
◆ For patients without bleeding and INR
rivaroxaban or
> 5 and < 9 due to warfarin, 1-2 mg of dabigatran.

Components
oral Vitamin K will bring INR within the
therapeutic range. For an INR ≥ 9, use
5-10 mg of oral vitamin K
◆ After intravenous administration, Vitamin K

effect can be detected after 2 hours and the


INR should be normalized after 12-24 hours
◆ SC and IM NOT recommended due

to variable absorption: intravenous


formulation can be used orally for
more rapid effect or if oral tablets
are not readily available

Pediatrics 43
Vitamin K dose:
■ INR > 5 & < 9: 1 to 2 mg oral
■ INR ≥ 9: 5 mg oral
■ Significant bleed in infants
and children: 5 mg IV OR
30 mcg/kg IV

30 31
Transfusion Basics
C O M P O N E N T S : Cryoprecipitate

A Basics22 B Indications

What 1. Treatment of microvascular or massive


■ Cryoprecipitate contains factor VIII (8), bleeding in patients with a fibrinogen
fibrinogen, and von Willebrand factor. concentration of less than 0.8 to
◆ Each unit of cryoprecipitate contains 1.0 g/L; or, patient’s clinical status
150 mg of fibrinogen highly suggestive of a low fibrinogen
concentration in the setting of massive
bleeding and clinical status precludes
How waiting for fibrinogen result before
■ Cryoprecipitate must be given through transfusion.
a blood administration filter (170-260
microns).

Red Blood
Cell Basics
2. Treatment of bleeding in patients
■ Cryoprecipitate is compatible ONLY with von Willebrand disease or
with normal saline. Hemophilia A only:
◆ when factor concentrates are

unavailable (remote geographic


Dose
region); and
■ 1 unit per 10 kg of body weight
◆ DDAVP is unavailable or ineffective
(i.e. 8 to 12 units per dose).
◆ Small adult: 8 units

◆ Large adult: 12 units

■ Each dose will increase the fibrinogen


by 0.5 g/L.22

Components
■ Recommended infusion time is 10-30
minutes per dose (maximum infusion
time 4 hours).
■ Half-life of fibrinogen is about 7 days.

32 33
R I S K C H A R T S : R e f e r e n c e f o r P h y s i c i a n s*

Risk Charts
RISK OF EVENT EVENT Risk of death per 1 unit component
(likely an under-estimate)
1 in 20 Febrile non-hemolytic transfusion reaction per pool ■ Note: patient risk should be determined as
of platelets a multiplication of the risk by the number
of units transfused (or ‘donor exposures’).
1 in 100 Minor allergic reactions (urticaria)
■ Serious Hazards of Transfusion Program
1 in 300 Febrile non-hemolytic transfusion reaction per unit of (United Kingdom) 1996-2004.
RBC (1 ‘donor exposure’) ◆ 1 in 270,000 components issued possibly,

probably or definitely related to patient


1 in 700 Transfusion-associated circulatory overload per death 44,45
transfusion episode

Transfusion Reactions
■ United States (Food and Drug
1 in 7,000 Delayed hemolytic transfusion reaction Administration) 2007.
◆ 1 in 428,846 components transfused
1 in 10,000 Transfusion-related acute lung injury (TRALI) resulted in a death from transfusion46
■ The Hemovigilance Network in France
1 in 10,000 Symptomatic bacterial sepsis per pool of platelets
1994-98.
1 in 40,000 ABO-incompatible transfusion per RBC transfusion episode ◆ 1 in 192,231 components transfused

resulted in a death from transfusion 47


1 in 40,000 Serious allergic reaction per unit of component

1 in 60,000 Death from bacterial sepsis per pool of platelets


SERIOUS HAZARDS OF TRANSFUSION (SHOT), UNITED KINGDOM
1 in 153,000** Transmission of hepatitis B virus per unit of component MAJOR ADVERSE EVENTS REPORTED 1996-2009 (6653 REPORTS) 44

Blood Conservation
1 in 250,000 Symptomatic bacterial sepsis per unit of RBC Incorrect component Inappropriate
transfused 40% transfusion 6%
1 in 500,000 Death from bacterial sepsis per unit of RBC
Storage errors 11%
< 1 in 1,000,000 Transmission of West Nile Virus
Others 1%
1 in 2,300,000 Transmission of hepatitis C virus per unit of component Infections 1%
Anti-D
TA-GvHD# 0.2% administration
1 in 4,000,000 Transmission of Chagas disease per unit of component
PTP†† 0.7% errors 11%
1 in 4,300,000 Transmission of HTLV per unit of component TACO† 0.8%
TRALI** 4% ATR* 19%
1 in 7,800,000 Transmission of human immunodeficiency virus (HIV)
Hemolysis 7%
per unit of component

* All of these risk frequencies are likely to have quite wide confidence intervals. * Acute transfusion reactions (ATR) include fever,
** Where time permits, consider hepatitis B vaccination in prospective transfusion allergic, anaphylactic, hypotensive reactions
recipients, especially for those requiring repeated infusions of blood or blood ** Transfusion-related acute lung injury (TRALI)
products (www.phac-aspc.gc.ca: Immunization Guide, part 4, pg. 194).
† Transfusion-associated circulatory overload (TACO)

†† Post-transfusion purpura (PTP)

# Transfusion-associated graft vs host disease (TA-GvHD)

34 35
R I S K C H A R T S : Reference for Patients

Risk Charts
RISK OF EVENT EVENT FREQUENCY OF NON-TRANSFUSION ASSOCIATED RISKS FOR
COMPARISON WITH RISKS OF COMPLICATIONS OF BLOOD TRANSFUSION
1 in 100 Hives (itchy skin rash)
1 in 300 Fever HAZARD PROBABILITY

1 in 700 Heart failure 1 in 10 48 Dying from lung cancer after smoking 1 pack a day for 30 years

1 in 7,000 Delayed hemolysis. Hemolysis is when your red blood 1 in 60 49 Stroke within 30 days of cardiac surgery
cells are destroyed
1 in 100 50 Death associated with hip replacement surgery
1 in 10,000 Lung injury
1 in 10,000 51 Annual risk of death in a motor vehicle crash

Transfusion Reactions
1 in 10,000 Symptomatic bacterial sepsis, per pool of platelets.
Sepsis is when you get an infection in your bloodstream 1 in 60,000 51 Annual risk of being murdered in Canada
or tissue
1 in 200,000 52 Death from anesthesia in fit patients
1 in 40,000 Wrong ABO (blood) group, per unit of red blood cells
1 in 300,000 53 Death from oral contraceptives age < 20 years
1 in 40,000 Anaphylaxis, which is an extreme sensitivity to a drug
or substance that can result in death 1 in 1,000,000 51 Annual risk of death from accidental electrocution in Canada
1 in 60,000 Death from bacterial sepsis, per pool of platelets 1 in 5,000,000 51 Annual risk of death from being struck by lightening in Canada
1 in 153,000 Hepatitis B Virus (HBV) transmission per unit of
component. Hepatitis is an inflammation of the liver.
HBV is a virus that is spread through contact with
infected blood, blood products and body fluids

Blood Conservation
1 in 250,000 Symptomatic bacterial sepsis, per unit of red blood cells
1 in 500,000 Death from bacterial sepsis, per unit of red blood cells
< 1 in 1,000,000 Transmission of West Nile Virus
1 in 2,300,000 Hepatitis C Virus (HCV) transmission, per unit of
component. Hepatitis is an inflammation of the liver.
HCV is a virus that is spread through injection drug
use, tattooing, and body piercing
1 in 4,000,000 Transmission of Chagas Disease. Chagas Disease is a
parasite that can be transmitted through transfusion
1 in 4,300,000 Human T-cell lymphotropic virus (HTLV) transmission,
per unit of component. HTLV is a virus that can be
transmitted by exposure to blood or sexual contact,
and can cause a form of cancer of the blood
1 in 7,800,000 Human Immunodeficiency Virus (HIV) transmission,
per unit of component. HIV is the virus that causes
AIDS. HIV attacks the immune system

36 37
T R A N S F U S I O N R E A C T I O N S

Risk Charts
A Reporting B Reaction by Symptom

!
Attention: All transfusion reactions (mild A T T E N T I O N SYMPTOM CONSIDER PAGE
to life-threatening) and transfusion-related
Report all transfusion
errors must be reported to the hospital’s reactions to your hospital’s Fever Management Algorithm 40
transfusion service (blood bank). transfusion service. Possible Reactions:
◆ Bacterial sepsis or contamination 41
What
◆ Acute hemolytic transfusion reaction 44
■ The transfusion service will investigate,
◆ Febrile non-hemolytic transfusion reaction (FNHTR) 46
assess and report the event to the

Transfusion Reactions
Transfusion Transmitted Injuries Surveillance
System (TTISS) at Public Health Agency Dyspnea Management Algorithm 47
of Canada*. In Québec, the hospital’s Possible Reactions:
transfusion service reports all transfusion ◆ Transfusion-related acute lung injury (TRALI) 48
reactions to Québec Hemovigilance System ◆ Transfusion-associated circulatory overload (TACO) 52
which then reports to TTISS.
■ Reactions relating to the quality of the Urticaria & Management Algorithm 54
product must be reported directly to Other Allergic Possible Reactions:
CBS/HQ. Reactions/ ◆ Anaphylaxis 55
Anaphylaxis ◆ Minor allergic reaction – Urticaria 57
How
■ CBS/HQ and Public Health Agency of
Canada* reporting forms are available Hypotension Management Algorithm 58

Blood Conservation
from all hospital transfusion services. Possible Reactions:
◆ Contact your transfusion service for more ◆ Bradykinin mediated hypotension 59
information
◆ It is the transfusion service’s responsibility Hemolysis Possible Reactions:
to submit them to CBS/HQ and Public after ◆ Acute hemolytic transfusion reaction 44
Health Agency of Canada transfusion ◆ Hemolysis not related to RBC alloantibodies 60
◆ In Québec, the transfusion service reports ◆ Delayed hemolytic transfusion reactions 61
all transfusion reactions to the Québec
Hemovigilance System which then reports Cytopenias Possible Reactions:
to TTISS (Transfusion Transmitted Injuries after ◆ Transfusion-associated graft vs host disease
Surveillance System) transfusion (TA-GvHD) 62
◆ Post-transfusion purpura (PTP) 64
* www.phac-aspc.gc.ca (click on Infectious Diseases; Blood Safety)
◆ Transfusion-related alloimmune

thrombocytopenia 65
◆ Transfusion-related alloimmune neutropenia 65

Virus, Parasite ◆ Viruses 66


and Prion ◆ Parasites 68
Infections ◆ Prions 69
◆ Other transfusion-transmissible agents 69

38 39
T R A N S F U S I O N R E A C T I O N S

Risk Charts
Fever BACTERIAL SEPSIS OR CONTAMINATION

MANAGEMENT ALGORITHM ETIOLOGY 54


■ Blood components may be contaminated by:
Fever (and/or Chills/Rigors) 1. Skin commensals from the donor (each
> 1ºC increase in temperature venipuncture may result in a small skin
AND temperature > 38ºC during or up to 4 hours post infusion plug that is retained in the donation bag)
2. Unrecognized bacteremia in the donor
3. Contamination from the environment
Immediate Management: or from handling of the product

Transfusion Reactions
1. Stop transfusion & maintain IV access ■ Organisms
2. Take patient’s vital signs ◆ Serious morbidity and mortality occur most
3. Re-check identification of patient & blood product frequently with gram-negative bacteria,55 Direct Smear Atlas: A CD-ROM of
4. Physician assessment required Gram-Stained Preparations of

FEVER
but are also reported with gram-positive Clinical Specimens. Lippincott
5. Notify hospital transfusion service (blood bank), skin bacteria Williams & Wilkins.
even if transfusion restarted or completed
◆ A number of bacteria have been implicated,

including:54,56
Clerical error or serious symptoms? Gram-negative Gram-positive
Temperature ≥ 39°C, hypotension/shock, tachycardia, rigors/chills,
• Escherichia coli • Staphylococcus aureus
anxiety, dyspnea, back/chest pain, hemoglobinuria/oliguria,
• Serratia marcescens • Staphylococcus
bleeding from IV sites, nausea/vomiting
• Klebsiella pneumonia epidermidis

Blood Conservation
• Pseudomonas species • Bacillus cereus
• Yersinia enterocolitica
No Yes

Administer acetaminophen 325 mg DO NOT RESTART TRANSFUSION INCIDENCE 47,54,55,57,58,59

BACTERIAL SYMPTOMATIC FATAL


CONTAMINATION SEPTIC REACTIONS BACTERIAL SEPSIS

Continue transfusion cautiously SUSPECT Buffy coat 1 in 1,000 1 in 10,000 1 in 60,000


under observation; likely a febrile 1. Hemolytic transfusion reaction; platelet pool
non-hemolytic transfusion reaction OR
1 unit of RBC 1 in 50,000 1 in 250,000 1 in 500,000
2. Bacterial contamination
• Collect blood bank samples to ◆ Bacterial sepsis accounts for at least 10% of transfusion-associated
Stop the transfusion if patient re-check ABO-group fatalities
develops any of the above symptoms • Clamp tubing, send unit to hospital ◆ Bacterial sepsis occurs most frequently with platelets due to their storage
blood bank along with attached
at 20-24ºC for preservation of function
IV solutions for bacterial cultures
and gram stain ◆ These figures were established prior to measures for bacterial detection
• Send first post-transfusion urine and may now be over-estimates
sample
• Send blood cultures on patient
taken from a different IV site

40 41
T R A N S F U S I O N R E A C T I O N S

Risk Charts
CLINICAL PRESENTATION PREVENTION
■ Clinical features of transfusion-associated ■ The skin is disinfected at the donation
sepsis may include: 58,60 site to reduce bacterial contamination
◆ Rigors, fever, tachycardia, hypotension,
by skin flora.
nausea and vomiting, dyspnea, disseminated ■ The first 40 mL of blood collected is
intravascular coagulation diverted and sequestered in a pouch
■ It is usually possible to culture the offending to reduce risk of transmitting organisms
organism from both the patient and the from skin (can be used for infectious

Transfusion Reactions
transfused product. agent testing).
■ There may be no immediate clinical signs
■ Apheresis and buffy coat platelets are
of bacterial infection after transfusion of cultured by CBS/HQ prior to issue to
bacterially-contaminated platelets, if the hospitals.

FEVER
!
bacterial load is small. ■ RBCs are stored at 1-6°C in a monitored A T T E N T I O N
blood bank refrigerator.
Keep RBCs in fridge or
MANAGEMENT 59,60 cooler until immediately

!
■ If transfusion-transmitted bacterial infection A T T E N T I O N prior to transfusion!
is suspected: Stop transfusion immediately
◆ Stop the transfusion! if bacterial infection is
◆ Notify the hospital transfusion service suspected.
(blood bank)

Blood Conservation
• Hospital transfusion service (blood bank)
will notify the supplier so that:
– other products from the same donor(s) can
be quarantined, cultured, and discarded AND
– any recipients of other products can be
identified and followed up

!
◆ Return residual of blood product(s) and A T T E N T I O N
tubing (clamped) for culture and gram
stain to the hospital transfusion service Arrange for Gram stain
on unit(s) suspected of
◆ Collect peripheral blood samples for being contaminated.
blood culture from a different site
◆ Provide aggressive supportive therapy as
appropriate, including broad-spectrum
antibiotics

!
A T T E N T I O N
• DO NOT WAIT FOR RESULTS OF
Start antibiotic therapy
BLOOD CULTURES PRIOR TO
immediately, do not wait
STARTING ANTIBIOTIC THERAPY
for results of blood cultures.

42 43
T R A N S F U S I O N R E A C T I O N S

Risk Charts
ACUTE HEMOLYTIC TRANSFUSION REACTION ■ Risk of death correlates with the amount
of incompatible blood transfused.63
ETIOLOGY
CLINICAL PRESENTATION 64
■ Acute hemolytic transfusion reactions may
be associated with: ■ Most common clinical presentation is:
◆ ABO-incompatibility ◆ Fever and chills

◆ Other blood group incompatibilities ◆ Hemoglobinuria

• There are 29 blood group systems ◆ Less common: pain, hypotension,

(in addition to ABO) that may cause nausea/vomiting, dyspnea, renal


incompatibility failure, DIC

Transfusion Reactions
◆ Rare cases when group O platelets with ■ Fever may be the only presenting sign of
high titers of anti-A and/or anti-B are an acute hemolytic transfusion reaction.
transfused to a non-group O recipient 61
■ ABO-incompatibility MANAGEMENT

FEVER
!
◆ ABO-incompatibility is due to a clerical ■ Stop the transfusion! A T T E N T I O N
error or other error in patient identification ■ Check if there is a clerical error. Check Stop transfusion immediately
• Most common cause of morbidity from identity of patient vs. patient identity if acute hemolytic
RBC transfusion on blood product label. reaction suspected.
◆ HALF of all errors are due to administering ■ Notify hospital transfusion service
properly labelled blood to the wrong (blood bank).
patient 62 ■ Send samples to hospital transfusion service
◆ Other errors are the result of improper
to re-check ABO-group.

Blood Conservation
labelling of samples or testing errors ■ Return residual of blood product(s) and
■ RBC alloantibodies (non-ABO) tubing (clamped) to the hospital transfusion
◆ Result from patient immunization from service.
a prior pregnancy or transfusion ■ Send first post-transfusion urine sample.
◆ Causes of reactions include:
■ Provide supportive care.
• Red cell alloantibodies in the patient’s ◆ Maintain good urine output
plasma below the level detected by
◆ Manage DIC and hemorrhage as clinically
the antibody screen
indicated
• Clerical error during patient antibody
screening PREVENTION
• Failure to detect RBC antibody due
■ Pay meticulous attention to identifying
to limitations of the laboratory assay
the patient and labelling the tubes at
• Uncrossmatched blood transfused sample collection (to ensure that patient
to a patient who is alloimmunized is assigned to the correct blood group).

!
INCIDENCE
■ Pay meticulous attention to verifying A T T E N T I O N
the patient’s identity, by checking Check the blood product
■ 1 in 38,000 red cell transfusions are their wristband, before transfusing. label with the patient’s arm
ABO-incompatible due to transfusing
◆ Confirm the patient’s identity (for patients band identification, NOT
the wrong blood to a patient.62
that are conscious) verbally in case the with a hospital card or chart.
■ Less than 10% of ABO-incompatible patient’s armband is incorrect (armband
transfusions result in a fatal outcome.62 errors do occur)
■ Over 50% of patients have no morbidity
from an ABO-incompatible transfusion.
44 45
T R A N S F U S I O N R E A C T I O N S

Risk Charts
FEBRILE NON-HEMOLYTIC TRANSFUSION Dyspnea
REACTION (FNHTR)
(Anaphylaxis is described under Allergic Reactions/Anaphylaxis)
ETIOLOGY
MANAGEMENT ALGORITHM
■ Attributable to:65
◆ Soluble factors (e.g., cytokines) in the Dyspnea
plasma of the component transfused
◆ Recipient antibodies, reactive to antigens

expressed on cells in the component, Immediate Management:


usually white blood cells 1. Stop transfusion & maintain IV access with 0.9% saline

Transfusion Reactions
INCIDENCE 66
2. Take patient’s vital signs
3. Re-check identification of patient & blood product

FEVER/DYSPNEA
INCIDENCE
4. Physician assessment required
RBC 1 in 300 5. Notify hospital transfusion service (blood bank)
6. Return clamped blood unit with tubing attached
Platelet pool 1 in 20

CLINICAL PRESENTATION
Consider:
■ Fever usually occurs during or up to 4 hours ■ TRANSFUSION-RELATED ACUTE LUNG INJURY (TRALI)
post transfusion.
■ TRANSFUSION-ASSOCIATED CIRCULATORY OVERLOAD (TACO)
◆ May be associated with chills, rigors, nausea,
■ ANAPHYLAXIS
vomiting and hypotension
■ If TRALI is suspected, notify hospital transfusion service

Blood Conservation
■ Fever is not always present (i.e., chills, nausea,
(blood bank) so that special donor and recipient testing
etc., alone). can be performed
■ Order STAT chest X-ray
MANAGEMENT
■ Oxygen, diuresis, and supportive care as required
■ Acetaminophen
■ Meperidine (Demerol®) 25-50 mg IV may be
effective for severe rigors if the patient has
no contraindications to meperidine.

PREVENTION
■ Pre-medication with acetaminophen and
diphenhydramine has not definitively been
shown to be effective in preventing
FNHTR.67,68
■ In patients with significant and recurrent
FNHTR, the following measures have been
used but efficacy is unproven:
◆ Acetaminophen, corticosteroids, fresh

components, plasma-depleted components,


washed red blood cells (washing platelets
results in 50% loss of platelets)
■ Antihistamines are not effective.

46 47
T R A N S F U S I O N R E A C T I O N S

Risk Charts
TRANSFUSION-RELATED ACUTE
LUNG INJURY (TRALI) 69,70

DEFINITION OF ACUTE LUNG INJURY (ALI) ETIOLOGY


RISK FACTORS FOR
■ Acute onset. ■ Presently not fully defined. Two postulated
ACUTE LUNG INJURY
■ Hypoxemia: mechanisms have been implicated:70,71
Predisposing factors
◆ PaO / FiO < 300 mmHg; OR 1. Antibody-mediated: Passive transfer
2 2 for ALI include:
◆ Oxygen saturation is
of HLA or granulocyte antibodies from
■ Direct Lung Injury donor to blood product recipient; or,
< 90% on room air; OR
• Aspiration less commonly, HLA or granulocyte
◆ Other clinical evidence

Transfusion Reactions
• Pneumonia antibodies in the recipient (antibodies
■ Bilateral lung infiltrates detected in donor or recipient in 80%
• Toxic inhalation
on the chest radiograph. of cases).72,73
• Lung contusion
No evidence of circulatory

DYSPNEA
■ • Antibodies are most common in
overload. • Near drowning
multiparous female donors as a
■ Indirect Lung Injury consequence of prior pregnancies
DEFINITION OF TRALI • Severe sepsis 2. Neutrophil priming hypothesis:
■ In patients with no evidence of • Shock Biologic response modifiers such
ALI prior to transfusion, TRALI • Multiple trauma as biologically active lipids in the
is diagnosed if: transfused component may induce
• Burn injury
◆ New ALI is present TRALI in a susceptible patient.74
• Acute pancreatitis
◆ It occurs during or within 6 hours
• Cardiopulmonary bypass INCIDENCE
of completion of transfusion

Blood Conservation
◆ There are no other risk factors
• Drug overdose ■ True incidence of this syndrome is
for ALI (see orange box to the right) unknown; two separate hospital-based
reports estimate TRALI at 1 in 1,200 to
DEFINITION OF POSSIBLE TRALI 5,000 plasma-containing transfusions,
respectively.72,75 (Both studies were
■ In patients with no ALI prior to
performed before TRALI reduction
transfusion, possible TRALI is
measures.)
diagnosed if:
◆ New ALI is present
■ The incidence of TRALI may be decreasing
with implementation of TRALI reduction
◆ It occurs during or within 6 hours
measures with SHOT reporting 50%
of completion of transfusion reduction in cases (see Prevention).44
◆ There are one or more risk factors
■ TRALI is known to be under-diagnosed
for ALI (see orange box to the right) and under-reported.

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Risk Charts
PRESENTATION MANAGEMENT
■ Dyspnea, hypoxemia, fever and hypotension. ■ Supportive care, including mechanical
■ Chest X-ray reveals interstitial and alveolar ventilation when clinically indicated.
infiltrates (pulmonary edema), without ■ Diuretics and steroids are not believed
elevated pulmonary pressures. to be useful in treating TRALI.78
■ Usually occurs with transfusion of RBCs, ■ Accurate reporting to hospital transfusion
platelets and plasma, but rarely with other service is critical to identify implicated donors

Transfusion Reactions
blood products (including cryoprecipitate and prevent TRALI in other recipients.
and IVIG). ■ Patient and donor testing should be
■ Almost always within the first 1-2 hours after arranged through the hospital transfusion

DYSPNEA
the start of transfusion but can be delayed service (testing performed through CBS).
for up to 6 hours.72
PREVENTION
■ Usually resolves in 24-72 hours.
■ 72% of reported cases required mechanical ■ Adherence to evidence-based transfusion
ventilation and death occurs in 5-10% of guidelines.
patients experiencing a TRALI reaction.72 ■ Component strategies to reduce TRALI
◆ TRALI is currently thought to be the most include:
common cause of transfusion-associated ◆ Plasma for transfusion predominantly from

fatalities 44,56 male donors

Blood Conservation
■ Milder forms of TRALI are thought to exist ◆ Buffy coat platelet pools suspended in male

and may present as transient hypoxia.76 plasma


■ Acute transient leukopenia may be observed ◆ Plateletpheresis collected from male donors

after a TRALI reaction.77 or never pregnant females


■ Deferral of donors confirmed to be
implicated in an episode of TRALI, and
with either antibodies or implicated in
Chest X-ray of a patient before and during an episode
of transfusion-related acute lung injury (TRALI) multiple episodes.

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Risk Charts
TRANSFUSION-ASSOCIATED CIRCULATORY
OVERLOAD (TACO) 79
ETIOLOGY PREVENTION
■ Circulatory overload results from: ■ Pre-transfusion assessment is important to
1. Impaired cardiac function, AND/OR identify patients at risk and management
2. Excessively rapid rate of transfusion should be adjusted accordingly.
■ Preventative measures include:

!
INCIDENCE ◆ Avoid transfusing more than one A T T E N T I O N

■ Current estimate of the frequency of unit at a time In patients at risk,


◆ Transfuse over longer periods avoid transfusing more
TACO is 1 in 700 transfusion recipients.

Transfusion Reactions
■ In perioperative surgery setting in older (maximum 4 hours) than one unit at a time.
◆ Pre-emptive diuretics
orthopedic patients, incidence is much
higher (1 in 100 patients).80 ◆ Components can be split into smaller

DYSPNEA
■ Patients over 60 years of age, infants, and aliquots to further reduce the speed
patients with severe euvolemic anemia of infusion without wasting product
(hemoglobin < 50 g/L) are particularly or increasing donor exposure
susceptible.

CLINICAL PRESENTATION
■ Clinical presentation includes: dyspnea,
orthopnea, cyanosis, tachycardia, increased
venous pressure, and hypertension.

Blood Conservation
MANAGEMENT
■ Interrupt the transfusion. A T T E N T I O N

!
■ Administer oxygen and diuretics as needed. Interrupt transfusion.
■ Consider restarting transfusion at a reduced Administer oxygen and
infusion rate if clinical status allows and diuretics if required.
product still viable. Consider restarting
■ Chest x-ray. transfusion at reduced rate.

52 53
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Risk Charts
Urticaria & Other Allergic Reactions/Anaphylaxis ANAPHYLAXIS

MANAGEMENT ALGORITHM ETIOLOGY 81


■ Vast majority of anaphylactic reactions are
Allergic Reaction unexplained.
A transfusion reaction that may be associated with urticaria, facial edema,
■ The following mechanisms have been implicated
airway edema, lower respiratory tract symptoms, hypotension, or shock in anaphylaxis/anaphylactoid reactions:
◆ Anti-IgA in an IgA deficient recipient

◆ Antibodies to polymorphic forms of

ALLERGIC REACTIONS/ANAPHYLAXIS
Transfusion Reactions
Immediate Management: serum proteins (IgG, albumin, haptoglobin,
1. Interrupt the transfusion & maintain IV access with 0.9% saline α-1-antitrypsin, transferrin, C3, C4, etc.)
2. Take the patient’s vital signs ◆ Transfusing an allergen to a sensitized patient

3. Re-check name of patient & name on blood product (e.g., penicillin, ASA, etc. consumed by
4. Physician assessment required donor)
5. Notify hospital transfusion service (blood bank) even if transfusion ◆ Passive transfer of IgE (to drugs, food)
restarted or already completed ■ 1 in 500 blood donors are IgA deficient
(IgA < 0.05 mg/dL), and 1 in 1,500 blood
donors have anti-IgA, but most are NOT at
Clerical error, anaphylaxis or serious symptoms? risk of an anaphylactic transfusion reaction
1. Hypotension (reasons are not clear at this time).82
2. Dyspnea/cough ■ Haptoglobin deficiency is not uncommon
3. Tachycardia
in Asian patients (1 in 1,000) and has been
4. Generalized flushing or anxiety

Blood Conservation
associated with anaphylactic reactions.83
5. Nausea/vomiting
6. Widespread rash > 2/3 body
INCIDENCE
■ Transfusion-associated anaphylactic shock
is rare.84
No Yes
■ Anaphylaxis accounts for approximately
3% of transfusion associated fatalities.56

Consistent with minor allergic reaction DO NOT RESTART TRANSFUSION


• Notify the patient’s physician STAT
• Notify the hospital transfusion
Give diphenhydramine 25-50 mg IV/po service (blood bank) immediately

Continue transfusion cautiously SUSPECT ANAPHYLACTIC REACTION


OR SEVERE ALLERGIC REACTION

Stop transfusion if patient develops


any of the above symptoms

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Risk Charts
MINOR ALLERGIC REACTION – URTICARIA

CLINICAL PRESENTATION 81 ETIOLOGY


■ Reactions usually begin within 1 to 45 ■ Unclear, but relates to factors in the
minutes after the start of the infusion. plasma portion of the component.
■ Cutaneous reactions (urticaria) are present
in the majority of anaphylactic and INCIDENCE
anaphylactoid reactions. ■ 1 in 100 mild urticarial reactions with
◆ When hypotension and hypoxia follow plasma-containing components.86

ALLERGIC REACTIONS/ANAPHYLAXIS
Transfusion Reactions
transfusion, examine skin for urticaria
(e.g., under drapes in operating room) CLINICAL PRESENTATION
■ Anaphylactic/anaphylactoid reactions are ■ One urticarial lesion to widespread urticarial
associated with upper or lower airway lesions.
obstruction (symptoms may include ■ May be associated with pruritis, erythema,
hoarseness, stridor, wheezing, chest pain, flushing, or mild upper respiratory symptoms
dyspnea, anxiety, feeling of impending (cough, wheezing), nausea, vomiting,
doom), hypotension, gastrointestinal abdominal cramps, or diarrhea.
symptoms (nausea, vomiting), rarely death.
Potentially life-threatening. MANAGEMENT

!
■ A T T E N T I O N
■ Interrupt the transfusion.
Interrupt transfusion.
TREATMENT
A T T E N T I O N
■ Give diphenhydramine 25-50 mg po or Give diphenhydramine.

!
■ Stop the transfusion! Do not restart. IV depending on severity of the reaction.
Stop the transfusion Restart transfusion slowly.

Blood Conservation
■ If severe urticarial reaction involving > 2/3 if patient has
■ Restart the infusion slowly only if:
body surface area: Stop the transfusion anaphylactic reaction. 1. The urticarial rash involves < 2/3
and do not restart. Administer 25-50 mg Do not restart. of the body surface area; and,
diphenhydramine.
2. There are no associated symptoms
■ Anaphylaxis – promptly administer suggesting a severe allergic reaction.
epinephrine, corticosteroids,
diphenhydramine, vasopressors, PREVENTION
and supportive care as required. ■ If the urticarial reactions are recurrent, the
■ Provide ventilatory support as indicated following precautionary measures may be
clinically. used although their efficacy is unknown:
Note: Epinephrine should be readily available ◆ Pre-medication with diphenhydramine
whenever transfusion is carried out.
and/or corticosteroids
◆ Plasma depletion of RBCs or platelets
PREVENTION OF RECURRENT ANAPHYLAXIS
◆ Washed RBCs or platelets
■ Pre-medication with intravenous steroids
and diphenhydramine.
■ If a patient is found to be IgA-deficient
with anti-IgA, the following products
are recommended:
◆ IgA-deficient blood products from IgA

deficient donors, available from CBS/HQ


◆ Washed RBCs (2L normal saline in

6 wash cycles) or platelets 81,85


56 57
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Risk Charts
Hypotension87 BRADYKININ MEDIATED HYPOTENSION

MANAGEMENT ALGORITHM ETIOLOGY


■ Bradykinin is believed to play a major
Hypotension role in generating hypotension.
> 30 mmHg drop in systolic or diastolic blood pressure*
■ Angiotensin-converting enzyme is the
main enzyme responsible for degradation
of bradykinin.
◆ Some individuals have a genetic
Immediate Management: polymorphism resulting in a decrease

Transfusion Reactions
1. Stop the transfusion in bradykinin degradation
2. Provide supportive care, including IV fluids
3. Consider differential diagnosis

HYPOTENSION
INCIDENCE
4. Physician assessment required ■ Unknown.

CLINICAL PRESENTATION
Consider: ■ Majority of hypotensive reactions
1. Acute hemolytic transfusion reaction occur with platelet transfusions.
2. Bacterial sepsis ■ Of reported cases, over half of the
3. Severe febrile non-hemolytic transfusion reaction patients were on ACE inhibitors.
4. Bradykinin mediated hypotension ■ Other symptoms may be present,
5. Transfusion-related acute lung injury
6. Anaphylaxis
including dyspnea, urticaria, nausea,

Blood Conservation
and vomiting.
■ Rarely associated with significant
morbidity or mortality.
No Yes
unrelated to transfusion TREATMENT
■ Detect early: Monitor the patient for A T T E N T I O N

!
the first 15 minutes and vital signs at Monitor patient for first
Possibly resume transfusion Do not restart transfusion. 15 minutes.
after reassessing Refer to appropriate sections. 15 minutes and vital signs
■ Stop the transfusion and do not re-start. at 15 minutes.
■ Provide supportive care, including Stop transfusion if
* Definition refers to adult patients only intravenous fluids. hypotension develops.
■ Consider acute hemolytic transfusion
reaction, sepsis, TRALI and allergic
reactions in the differential diagnosis.

PREVENTION
■ In cases where ACE inhibitors were
implicated, consider (where possible)
an alternative anti-hypertensive prior
to additional transfusions.

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Hemolysis after Transfusion DELAYED HEMOLYTIC TRANSFUSION
REACTIONS
ETIOLOGY
HEMOLYSIS NOT RELATED
TO RBC ALLOANTIBODIES ■ Results from the formation of antibodies
in the recipient (to transfused red cell
■ Hemolysis may also occur in the following alloantigens or from RBC antigen exposure
settings and should be considered in the during a prior pregnancy) and below the
differential diagnosis of hemolysis after level of detection on the initial antibody
transfusion: screen testing.
◆ Use of hypotonic IV solutions with
■ Commonly implicated antigens are

Transfusion Reactions
RBC transfusions (in order of frequency): E, Jka, c, Fya, K.88
◆ Medical device-related (e.g., cell saver
■ Delayed hemolysis may occur with transfusion-
or blood warmer malfunction)

HEMOLYSIS
transmitted malaria and babesiosis.
◆ Overheating of RBCs due to improper

storage (e.g., RBCs placed on radiator) INCIDENCE


◆ Freezing of RBCs (e.g., transport of blood
■ 1 in 6715 units of RBCs transfused are
directly on ice or storage in freezer) associated with a delayed hemolytic
◆ Transfusion of RBCs under pressure transfusion reaction.88
through a small bore needle
◆ Transfusion of outdated RBCs CLINICAL PRESENTATION
◆ Non-transfusion-related causes ■ 3 days to 2 weeks after transfusion, the
■ Most are benign, but life-threatening patient presents with hemolytic anemia (low

Blood Conservation
hemolysis with severe anemia and hemoglobin, high bilirubin, reticulocytosis,
renal failure may occur. spherocytosis, high LDH, positive antibody
screen, and a positive direct anti-globulin
test).89

COMPLICATIONS
■ Most are benign, but life-threatening
hemolysis with severe anemia and renal
failure may occur.

TREATMENT
■ Transfuse compatible blood (‘antigen
negative’; i.e., if the offending antibody
is anti-Jka, then the transfusion service
will provide units that do not carry the
Jka antigen).

PREVENTION
■ Avoid RBC transfusions.
■ Use of antibody screening methods with
maximal sensitivity.
■ Notify patient and provide an antibody
card for the patient to carry in their wallet.
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Cytopenias after Transfusion

TRANSFUSION-ASSOCIATED GRAFT
VS HOST DISEASE (TA-GVHD) 90,91
ETIOLOGY TREATMENT
■ TA-GvHD has been reported in ■ Largely ineffective.
immunocompromised patients or in Recipient ■ Survival (which is rare) is attributed to
immunocompetent individuals transfused immunosuppressive therapy.
a haploidentical product (the risk of an

Tolerance

Rejection

Transfusion Reactions
HLA-haploidentical donor in North America PREVENTION
is estimated at 1 in 17,700 to 39,000).92 ■ For patients at risk (see below), it is critical
◆ A donor who is homozygous for an

CYTOPENIAS
to irradiate cellular blood components
HLA type (haploidentical), whose blood (RBC and platelets).
product is transfused to a recipient who
is heterozygous for the same HLA type
PATIENTS REQUIRING IRRADIATED BLOOD 93
and a different HLA type places the Donor
recipient at risk ■ Patients with congenital
HLA-haploidentical immunodeficiency states
• The donor’s lymphocytes mount a reaction
against the non-matching HLA determinants ■ Intrauterine transfusions
on the recipient’s cells ■ Neonatal exchange transfusions

!
A T T E N T I O N
INCIDENCE
■ Patients with lymphoproliferative diseases

Blood Conservation
■ Patients undergoing bone marrow or Immunocompromised
■ Unknown; there were 13 cases reported patients must receive
stem cell transplants
in the UK SHOT program from 1996 to irradiated blood.
2001 with no further reports up to 2009.44 ■ Recipients of directed transfusions from
family members
CLINICAL PRESENTATION ■ Recipients of HLA-matched platelets
■ Fever, rash, liver dysfunction, and diarrhea ■ Patients treated with purine analogs
commencing 1-2 weeks post-transfusion (e.g., fludarabine), purine antagonists
followed by pancytopenia later. (e.g., bendamustine), alemtuzumab
■ Overwhelming infections are the most and anti-thymocyte globulin
common cause of death.
■ Mortality is > 90%. ■ Notify patient in need of irradiated blood
■ Diagnosis can be made by biopsy of skin, and provide a card for the patient to carry
liver, or bone marrow. in their wallet.
■ Confirmation requires documentation of the
presence of donor lymphocytes (e.g., HLA
typing, short tandem repeat analysis).

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Risk Charts
POST-TRANSFUSION PURPURA (PTP) 94
ETIOLOGY TREATMENT
■ Transfusion of platelet antigen-positive ■ Test patient plasma for platelet-specific
RBCs, plasma, or platelets to a patient antibodies (performed at CBS/HQ).
who lacks the same platelet antigen. ■ Thrombocytopenia lasts approximately
◆ 75% of cases occur in an HPA-1b (Human 2 weeks.
Platelet Antigen-1b) homozygous patient ■ First-line therapy is IVIG at a dose of
who is transfused HPA-1a positive blood 1 g/kg daily for 2 days; the platelet count
products is expected to increase 4 days after the
◆ 3% of the North American population start of therapy.

Transfusion Reactions
are HPA-1b homozygotes, but only
28% appear able to form anti-HPA-1a PREVENTION

CYTOPENIAS
■ Autologous platelet destruction occurs ■ Patients with PTP should receive antigen-
but the mechanism is unclear. negative RBC and platelet transfusions
(washed RBCs do not appear to be safe
INCIDENCE in this population).
■ Unknown; more than 300 cases have been
reported in the medical literature. WARNING
■ Affected patients (and their relatives)
CLINICAL PRESENTATION are at risk of neonatal alloimmune
■ There are 5 times as many female transfusion thrombocytopenia (NAIT). The family
recipients with PTP as males, as a consequence should be tested and counselled

Blood Conservation
regarding both PTP and NAIT.

!
of sensitization in a previous pregnancy.
◆ NAIT occurs when a woman has
■ Occurs post-transfusion at a mean of nine A T T E N T I O N
days (range 1 to 24). anti-platelet antibodies (usually
anti-HPA-1a) and is carrying an antigen- Patients affected by PTP,
■ Platelet count is less than 10 x 109/L in 80% are at risk of NAIT.
positive fetus; the infant is frequently
of cases.
born with severe thrombocytopenia,
■ Mortality is 8% and the majority of deaths and sometimes, intracranial hemorrhage
are from intracranial hemorrhage.
■ Transfusions are frequently associated with
fever, chills, rigors, and bronchospasm. TRANSFUSION-RELATED ALLOIMMUNE
■ Differentiation from straightforward platelet THROMBOCYTOPENIA
alloimmunization is problematic. ■ Uncommon cause of thrombocytopenia.
◆ PTP should be considered when a platelet
■ Due to platelet specific donor alloantibodies
refractory patient fails to respond to to patient platelet antigens.95
HLA-matched platelets

TRANSFUSION-RELATED ALLOIMMUNE
NEUTROPENIA96
■ Rare cause of neutropenia.

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Risk Charts
Virus, Parasite and Prion Infections Cytomegalovirus (CMV): 101,102,103
(Bacterial contamination is described under Fever)
■ 40% of Canadian blood donors have
antibodies to and harbour CMV in their
white cells, but without clinical consequences.
VIRUSES ■ Transmission is vertical from mother to child,
or by body fluids, sexual activity, transfusion,
Risks or transplantation.
■ Donating blood in the ‘window period’ – the
■ CMV-seronegative units are available from
interval between the time of infectivity and the
CBS/HQ for restricted use only. The most

VIRUS, PARASITE & PRION INFECTIONS


appearance of detectable disease markers such
commonly recommended indications for

Transfusion Reactions
as specific antibodies or viral nucleic acid sequences.
CMV-seronegative products are:
■ Current ‘window period’ estimates are:97
1. CMV-seronegative pregnant women
◆ 10 days for HIV
2. Intrauterine transfusions
◆ 8 days for HCV
3. CMV-seronegative allogeneic bone
◆ 38 days for HBV
marrow transplant recipients
■ Figures in chart below are risk per donor HIV Virus ■ Leukoreduction removes most, but not
exposure: (i.e. 1 unit of RBC) all CMV from blood components.104
HIV 1 in 7.8 million97 ■ The incremental benefit of providing
CMV-seronegative components, in addition
Hepatitis C virus (HCV) 1 in 2.3 million97 to leukoreduction, in the prevention of
CMV transmission is unknown.
Hepatitis B virus (HBV) 1 in 153,00097

Blood Conservation
Human T-cell lymphotropic virus 1 in 4.3 million97
West Nile Virus (WNV)
West Nile Virus (WNV) < 1 in 1 million98 ■ No reported cases of transfusion transmitted
WNV in Canada since nucleic acid testing of
donations began in 2003.105
■ Outcomes of transfusion-related
transmission of HIV, HCV, HBV and HTLV: ■ Since 2003 in the USA, there have been
9 confirmed cases of transfusion-transmitted
VIRUS OUTCOME WNV.106,107
■ Facts about transfusion-transmitted WNV:
HIV Chronic infection with progressive loss of CD4+ lymphocytes
◆ The virus can be transmitted through RBCs,
leading to opportunistic infections, immune system dysfunction,
and direct viral effects on multiple organ systems.99 platelets, plasma, and cryoprecipitate, but
not through manufactured blood products
HCV 80% of recipients develop chronic HCV. 30% develop severe (e.g., albumin, IVIG, clotting factor
progressive hepatitis with long-term consequences of cirrhosis concentrates)
and risk of hepatocellular carcinoma.100
◆ The onset of symptoms post-transfusion

HBV The vast majority of cases resolve by developing immunity. In less has ranged from 3 to 13 days (median
than 5% of cases, chronic infection occurs with the likelihood of 7 days)
chronic liver disease. Rarely, HBV presents as acute fulminant ◆ Symptomatic recipients were primarily
hepatitis.100 immunocompromised patients; however,
HTLV Long-term consequences of transfusion-transmitted HTLV remain post-partum and post-operative patients
unclear, but the virus is associated with the development of HTLV- have been affected
associated lymphoma and myelopathy in the endemic form.99

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Risk Charts
PARASITES PRIONS

Chagas Disease Variant Creutzfeldt-Jakob Disease (vCJD)


■ Chagas Disease is caused by the protozoan ■ 4 suspected cases of transfusion-associated
Trypanosoma cruzi found predominantly transmission have been reported in the
in Central and South America. U.K.110
■ Acute infection is often unrecognized but ■ 1 suspected case of transmission from
if untreated, can lead to chronic infection U.K.-derived Factor VIII concentrate.111
including cardiac involvement in 30%. ■ At present, high risk blood donors (resident

VIRUS, PARASITE & PRION INFECTIONS


■ The protozoan is transmitted through in the UK or France for more than 3 months,

Transfusion Reactions
contact with feces of an infected or Saudi Arabia for more than 6 months Public Health Agency of Canada

triatomine bug but can also be between 1980-1996, or in Europe for more
transmitted from mother to child or than 5 years since 1980) are deferred in
through transfusion or transplantation. Canada.
■ There have been 7 reported cases of
transfusion transmitted Chagas in US and OTHER TRANSFUSION-TRANSMISSIBLE
Canada, mostly with platelet products.108 AGENTS 107,108,112
■ Since May 2010, at risk donors in ■ Other rare infectious agents confirmed to
Canada are tested for Chagas disease.
be transmitted by blood components that
■ The current risk of transfusion- may cause symptomatic infection include:
transmission is estimated to be ◆ Viral – Parvovirus B19, Hepatitis A,
1 in 4 million, based on U.S. data.109
Dengue, Chikungunya, Tick-borne

Blood Conservation
encephalitis, Colorado Tick Fever,
Human Herpes Virus 8, SEN virus
and Simian foamy virus
◆ Protozoal – Malaria, Babesiosis,

Leishmaniasis, Toxoplasmosis
◆ Helminthic – Filariasis

◆ Spirochetal – Treponema pallidum (Syphilis)

◆ Rickettsial – R. rickettsii (Rocky Mountain

Spotted Fever), R. burnetii (Q fever),


Ehrlichia (Ehrlichiosis)
■ It is extremely important to report cases of
the above infections in transfusion recipients
and recent blood donors.
■ The following agents are transfusion-
transmissible but have not been established
as causing disease in man: TT virus, SEN virus,
Simian foamy virus and XMRV.

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Complications of Massive Transfusion
Definition ■ Risk of clinically important hypothermia
■ More than 10 units of RBCs, or, transfusing is significantly increased by infusion of
more than one blood volume in a 24-hour 5 or more units of blood.117
period. ■ Consequences of hypothermia:
■ Massive transfusion is an independent risk ◆ Platelet dysfunction
factor for developing multi-organ failure.113 ◆ Decreased coagulation factor activity

◆ Reduced clearance of citrate


Complications114
◆ Decreased cardiac output

Transfusion Reactions
■ The complications described below are

MASSIVE TRANSFUSION
dependent on the following factors: ◆ Hypotension

◆ Number of units transfused ◆ Arrhythmias (especially if cold blood is

◆ Rapidity of transfusion transfused rapidly through a central line)


◆ Patient factors
3. Hypocalcemia/Hypomagnesemia/
1. Dilutional coagulopathy Citrate toxicity
■ 50% of massively-transfused patients
■ Citrate is the anticoagulant used in blood
develop an INR > 2.0 and about 33% components.
have thrombocytopenia with a platelet ■ It is usually rapidly metabolized by the liver.
count < 50 x 109/L.115 ◆ A normothermic adult not in shock can

!
■ Number of RBCs transfused does not A T T E N T I O N tolerate upwards of 20 units per hour
accurately predict the need for platelet Use laboratory monitoring without calcium supplementation

Blood Conservation
and FP transfusion; frequent laboratory where possible to guide the ■ With massive transfusion, the capacity
measurements are required to guide use of blood components. of the liver to degrade citrate may be
transfusion decisions. overwhelmed.
■ Although formula replacement of blood ■ Citrate binds ionic calcium and
components is not recommended, it may magnesium, causing functional
be required when coagulation tests are hypocalcemia, hypomagnesemia,
not rapidly available.116 and also metabolic alkalosis (from
bicarbonate, a metabolite of citrate).
2. Hypothermia ■ Clinical symptoms include: hypotension,
■ Rapid infusion of cold blood can result narrow pulse pressure, elevated pulmonary
in cardiac arrhythmias. artery pressure, tetany, paresthesia and
■ Prevention is critical – if massive arrhythmias.
transfusion is likely, use an approved ■ If hypocalcemia develops OR patient
and properly maintained blood warmer. develops signs or symptoms of
■ Mortality after massive transfusion is hypocalcemia then administer:
inversely related to core temperature ◆ 1 gram (1 ampoule) of calcium chloride
(data from 1987):117 IV at maximum rate of 100 mg/minute
◆ < 34ºC - 40%

◆ < 33ºC – 69%

◆ < 32ºC – 100%

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Risk Charts
4. Metabolic acidosis TIPS DURING MASSIVE TRANSFUSION/BLEEDING
■ Rare; from acid pH of blood products.
■ Monitor core temperature.
■ Usually, metabolic alkalosis occurs due
to bicarbonate production from citrate
■ Prompt use of measures to prevent
metabolism. hypothermia, including use of a blood
warmer for all IV fluids and blood
■ May be an indicator of lactic acidosis components.
in patients with tissue hypoperfusion.
■ Watch for dilutional coagulopathy.

Transfusion Reactions
5. Hyperkalemia118 ◆ While patient is actively bleeding,

MASSIVE TRANSFUSION
■ Release of potassium from stored RBCs transfuse to keep:
increases with storage time and after • Platelet count > 50 x 109/L
irradiation. (with head injury > 100 x 109/L)
■ Potassium concentration in a SAGM-RBC • INR < 1.5
unit is approximated by the number • Fibrinogen > 1.0 g/L
of days of storage (110 mL of ■ Watch for hypocalcemia, acidosis and
supernatant/unit). hyperkalemia.
◆ For example, a 42 day old RBC ■ Use SQ40 SE Pall ® filter with blood
has a potassium concentration tubing to minimize the number of times
of approximately 45 mmol/L119 the blood tubing has to be changed.
■ Order bloodwork q1h (e.g., CBC, INR, ◆ Change SQ40 SE filter q10 RBC units

PTT, fibrinogen, calcium, arterial blood or if blocked (and change blood tubing

Blood Conservation
gas, potassium). within the number of hours specified by
Note: For discussion of the changes in electrolytes and hospital policy)
acid-base balance with massive transfusion, see Wilson ◆ Change blood tubing q2-4 RBC units if
et al.120 SQ40 SE not used

72 73
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Risk Charts
Blood Conservation in the Perioperative Setting Blood Conservation Strategies
The following blood conservation strategies
are available, listed according to when they
■ There are currently several perioperative A T T E N T I O N
should be implemented perioperatively:

!
blood conservation strategies available Offer patients blood
to patients. conservation strategies if TIME UNTIL SURGERY BLOOD CONSERVATION STRATEGIES AVAILABLE PAGE
■ Patients that are at high risk of perioperative they have a > 10% chance
transfusions (> 10% chance of allogeneic of blood exposure.
RBC transfusion) should be identified as > 35 days ◆ Investigate and treat anemia –
early as possible, preferably at least 28 days ◆ Delay surgery until anemia corrected –
before surgery, to allow institution of ◆ Iron 78

Transfusion Reactions
appropriate blood conservation modalities.
◆ As transfusion risk varies from institution
14-35 days ◆ Delay surgery until anemia corrected –
to institution and surgeon to surgeon for ◆ Autologous blood donation 80
the same procedure, each institution must
determine its own requirements for ◆ Erythropoietin weekly dosing regimen 86
transfusion ◆ Iron 78

Likelihood of Transfusion 10-13 days ◆ Delay surgery until anemia corrected –


■ The likelihood of transfusion is proportional ◆ Erythropoietin daily dosing regimen 86
to the preoperative hemoglobin level of the ◆ Iron 78
patient.
◆ Shown here is the probability of transfusion
< 10 days ◆ Delay surgery until anemia corrected –

Blood Conservation
for patients undergoing cardiac surgery121 before surgery
Intraoperative ◆ Attention to surgical hemostasis 76
◆ Antifibrinolytics and DDAVP 88, 90
◆ Intraoperative cell salvage 84
◆ Regional anesthesia 90
◆ Topical hemostatic agents (e.g., fibrin 90
sealants)
◆ Other measures, mainly investigational 91
◆ Adherence to strict transfusion guidelines 20

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Charts
Risk Risk
1. GOOD SURGICAL TECHNIQUE
■ Using good surgical technique(s) is critically ■ Dabigatran (Pradax™)

Paitent
important in reducing a patient’s exposure ◆ Consider stopping therapy 2-4 days before major

to allogeneic blood. surgery in patients with normal renal function


◆ In patients with renal dysfunction (creatinine
Recommended surgical practices
clearance < 50 mL/min) consider stopping
■ The following good surgical practices are
4-5 days before major surgery
highly recommended:
◆ Assess and treat nutritional status
■ Rivaroxaban (Xarelto®)
◆ Consider stopping therapy 2-3 days before major
preoperatively
◆ Careful ligation of blood vessels
surgery in patients with normal renal function

Transfusion Reactions
◆ In patients with renal dysfunction (creatinine
◆ Avoid tissue trauma
clearance < 50 mL/min) consider stopping
◆ Optimal use of electrocautery
3-4 days before major surgery
◆ Meticulous attention to surgical hemostasis

◆ Utilize avascular tissue planes


■ NSAIDs
◆ Consider stopping therapy 4-7 days
◆ Appropriate use of topical hemostatic agents
before major surgery
◆ Prevent and treat coagulopathy associated
◆ Celecoxib does not inhibit platelet
with massive transfusion
aggregation at usual doses
Consider stopping anti-platelet and
anticoagulants before major surgery Minimize blood sampling and loss123
■ Acetylsalicylic Acid (Aspirin®) and
■ Restrict diagnostic phlebotomy.
Clopidogrel (Plavix™)122 A T T E N T I O N
■ Use small volume tubes and testing methods.

!
■ Conduct bedside microanalysis.

Blood Conservation
◆ Primary prevention: 48 hours minimum,
Do not stop ASA or
7-10 days preferable clopidogrel without
■ Remove arterial and venous catheters when
◆ Secondary prevention (after remote MI, consultation of patient’s no longer necessary.
stroke, peripheral artery disease) cardiologist or neurologist,
if: Preoperative patients on Warfarin:124
• low risk of bleeding procedure (e.g., cataract
■ If low risk of thromboembolic events (e.g.,
surgery, plastic surgery): no need to stop • recent thrombosis
primary prophylaxis of atrial fibrillation):
ASA or clopidogrel (MI, stroke)
◆ Stop warfarin 4-5 days preoperatively;
• high risk of bleeding procedure (e.g., • recent percutaneous
repeat INR 1 day preoperatively
neurosurgical procedure): 48 hours coronary intervention
◆ If INR > 1.5 then give 2 mg oral vitamin K
minimum, 7-10 days preferable (PCI)
◆ Then repeat INR preoperatively
◆ Secondary prevention (high risk for arterial • coronary stent in
thrombosis – recent percutaneous coronary last 12 months ■ If high risk of thromboembolic events
intervention, MI, stroke OR coronary stent (e.g., recent deep vein thrombosis):
◆ Consider switch to unfractionated or
< 12 months)
• consult patient’s cardiologist or neurologist low molecular weight heparin 4 days
for expert advice preoperatively; consult with hematology
• only stop ASA and clopidogrel if risk of on timing and preferred regimen
bleeding exceeds risk of cardiovascular ■ For urgent (< 6 hours) reversal of Vitamin K
complications antagonist effect prior to surgery (see pages
120-121).125
◆ Prothrombin Complex Concentrates

◆ Vitamin K I.V.

76 77
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Charts
Risk Risk
2. IRON COMMONLY USED IRON REPLACEMENT THERAPIES DOSE MG ELEMENTAL MG
■ Very little data are available in the

Paitent
Ferrous gluconate 300 35
literature on the efficacy of iron in
perioperative patients. Ferrous sulfate 300 60
■ There are several randomized trials of Ferrous fumarate (Palafer®) 300 100
iron therapy administered perioperatively,
finding that: Polysaccharide-iron complex (Triferex®) 150 150
◆ Preoperative iron may be helpful for Proferrin 398 11
patients with low preoperative hemoglobin
levels, but not confirmed beneficial in all Common Adverse Events*

Transfusion Reactions
studies126,127,128,129 ■ GI upset (diarrhea, nausea, constipation).
◆ Randomized trials failed to confirm a
A T T E N T I O N ■ Dark stools.

!
benefit of post-operative iron therapy
Routine post-operative iron * See product monograph for details
in patients that were not anemic
therapy in preoperatively
preoperatively130,131,132,133,134,135
non-anemic patients
is NOT useful. INTRAVENOUS IRON
Dosage ■ There is currently insufficient evidence to
■ 150-200 mg of elemental iron/day for: support the routine use of intravenous iron
◆ patients with pre-operative iron deficiency in elective surgery patients or in conjunction
◆ Iron should be administered on an empty
with autologous blood donation.137
stomach for maximal absorption ■ Patients with iron deficiency anemia (whose
■ Vitamin C (ascorbic acid) as an adjunct
surgery should not be delayed to allow for
A T T E N T I O N

Blood Conservation
oral iron therapy to correct the anemia) may
to increase iron absorption is not

!
Ensure anemic patient be treated with intravenous iron, in addition
recommended if the elemental iron is prescribed 150-200 mg to oral iron.138
dosage is > 60 mg.136 of elemental iron
Dosage
(e.g., ferrous fumarate
300 mg po b.i.d. OR ferrous ◆ Check your hospital’s formulary to determine
sulfate 300 mg po t.i.d.). the recommended type of parenteral iron
(iron dextran or iron sucrose)
◆ Review the risks identified in the product
monograph and inform your patient about
the risks
◆ Give only sufficient iron to correct the
anemia (e.g., 1000 mg of elemental iron)
◆ Do not attempt to give a full replacement
dose as the patient can replete their iron stores
with oral iron in the post-operative period
◆ If considering iron therapy, it is important to
measure patients iron status to ensure iron
therapy will not lead to iron overload

78 79
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Charts
Risk Risk
PREOPERATIVE AUTOLOGOUS BLOOD DONATION (PAD)

Paitent
General Principles Which Patients Are Eligible?
■ Avoid automatically referring all patients ■ Patients with at least a 10% chance of
who are having major surgery – it is over- blood exposure during elective surgery
simplistic and should be discouraged.139 O D D S R AT I O should be considered. At some hospitals
■ Autologous blood donation reduces but this may include:145
The odds ratio is a way
does not eliminate the need for allogeneic ◆ cardiac surgery146,147
of comparing whether
blood.140 the probability of a ◆ major vascular surgery

◆ 9% of autologous donors undergoing certain event is the same ◆ revision hip replacement A T T E N T I O N

!
for two groups. An odds

Transfusion Reactions
elective surgery receive allogeneic blood ◆ major spine surgery
ratio of 1 implies that the The same criteria should
in addition to autologous blood141
◆ radical prostatectomy be used for transfusing
◆ Autologous blood donation reduces
event is equally likely
in the two groups. ◆ hepatic resection allogeneic blood and
the chance of allogeneic transfusion autologous blood.
An odds ratio of less
(odds ratio 0.17, 95% CI 0.08-0.32), but than one implies that Risks and Benefits of Autologous
increases the likelihood of all transfusions the event (e.g., allogeneic Transfusion at the Time of
(autologous plus allogeneic; odds ratio transfusion) is less likely; RISKS AT DONATION
Collection and Transfusion
3.03, 95% CI 1.70-5.39) in randomized conversely, an odds ratio It is unclear at the present time 1. Severe reaction at time of
studies142 greater than 1 implies if autologous blood transfusion is donation, requiring hospitalization,
■ Each institution should have a policy, that the event (e.g., any safer than allogeneic transfusion. (loss of consciousness and cardiac
based on its current blood exposure transfusion) is more likely. ischemia) is estimated at 1 in
rates, to guide the use of PAD. ◆ Autologous blood should only
16,783 donations (12-fold higher
be collected from patients with
risk than for volunteer donors).149

Blood Conservation
Cost-effectiveness of Autologous a greater than 10% chance of
allogeneic blood exposure 2. Iatrogenic anemia – average
Blood Donation
10 g/L hemoglobin drop per
■ Studies suggest poor cost-effectiveness143,144
unit donated.148
mainly because: BENEFITS148 3. Unit lost, damaged, or
◆ The risks of viral transmission by allogeneic
1. Possibly reduces post-operative prematurely discarded.
blood are very low
infections. 4. Surgery cancelled, resulting
◆ The cost of autologous blood collection
2. Reduces demand on allogeneic in outdated autologous unit.
is higher than that for allogeneic
blood supplies.
transfusion RISKS AT TRANSFUSION148
◆ The wastage rate of autologous blood
3. Reduces transfusion-transmitted
infections. 1. Bacterial contamination.
is high (30-50% of units are discarded) 2. ABO-incompatible transfusion
4. Avoids red cell alloimmunization.
(wrong blood given to the
5. Prevents some adverse
patient)
transfusion reactions (febrile
reactions, transfusion-related 3. Transfusion-associated
acute lung injury, allergic circulatory overload.
reactions, and delayed 4. Transfusion of allogeneic blood
hemolytic transfusion reactions). when autologous available.

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Charts
Risk Risk
Technical Aspects ACUTE NORMOVOLEMIC HEMODILUTION (ANH) 152

Paitent
AVAILABILITY
Principles
■ Autologous blood donation is available ■ Very little data on the efficacy and safety
through CBS/HQ, and some hospitals. of ANH and its widespread use at this time
◆ Request for autologous collection cannot be recommended.140,153
form available from CBS or HQ ■ Whole blood is withdrawn when anesthesia is
initiated and is replaced with crystalloid/colloid

!
TIMING to maintain normovolemia.
■ For optimal benefit, all units should be A T T E N T I O N ■ The blood is stored at room temperature (RT)

Transfusion Reactions
collected between 21 and 34 days prior Do not collect blood in the in the operating room (on a continuous rocker;
to surgery to allow for regenerative 2 weeks prior to surgery. stored at RT for 8 hours) and re-transfused
erythropoiesis.150 after bleeding ceases or if the patient has
an unacceptably low hemoglobin level.
DAYS UNTIL SURGERY WHEN 1ST UNIT COLLECTED
Indication
■ It is uncertain which patient populations
would best benefit from the use of ANH.
◆ ANH may be useful in patients with

excellent physical health (ASA I)


STORAGE undergoing major surgery with
■ Current Canadian standards allow that predicted large intraoperative
autologous red blood cells can be stored blood loss

Blood Conservation
◆ ANH may be an acceptable alternative
for 42 days as RBC (see page 10).
◆ Usually 1-3 units are collected depending on
for some Jehovah’s Witnesses
the anticipated need for transfusion
◆ 250 mL frozen plasma available from CBS

autologous donation (on physician’s order)

ORAL IRON
■ Oral iron is recommended only for patients
with reduced iron stores.
◆ In the absence of reduced iron stores

neither intravenous nor oral iron enhance


the success of autologous blood collection151

COMMON EXCLUSION CRITERIA FOR PAD


1. Recent myocardial infarction or unstable
coronary syndrome (last 6 months)
2. Stenotic valvular heart disease
3. Anemia (hemoglobin level requirement
is set by the blood centre or hospital
policy; generally 120 g/L)
4. Bacterial infection

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Charts
Risk Risk
Efficacy and Safety of ANH Indication
■ The medical literature is controversial ■ Meta-analysis of 75 studies:156

Paitent
on the efficacy and safety of ANH. ◆ Cell salvage in orthopedic surgery (all types

of salvage devices, washed and unwashed)


EFFICACY
• Relative risk of transfusion 0.46 (95% CI
◆ A meta-analysis of 42 trials including a 0.37-0.57)
total of 2,233 patients found that acute ◆ Cell salvage in cardiac surgery (unwashed only)
normovolemic hemodilution (ANH):153
• Relative risk of transfusion 0.77 (95% CI
• did not affect the likelihood of receiving 0.69-0.86)
allogeneic transfusion ◆ No increase in adverse events in the

Transfusion Reactions
• produced a small reduction in perioperative treatment group
blood loss and volume of allogeneic blood ◆ Consider in the setting of: trauma, hepatic
transfused
resection, major orthopedic and spine
◆ Theoretically, ANH is only of value if at least surgery, or ruptured aneurysm with
4 units of whole blood are removed by a appropriate quality assurance
trained physician and total blood loss expected ◆ Meta-analysis of 31 randomized controlled
is > 3 L, given that the patient has: trials, including 2282 patients, in the setting
• a high starting hemoglobin (> 130 g/L) of cardiac surgery found that cell salvage
• no renal insufficiency decreased the risk of allogeneic blood
• no history of cardiovascular disease exposure (OR 0.63, 95% CI 0.43-0.94,
Note: Risk of transfusion-associated circulatory P=0.02)157
overload at time of re-infusion. ◆ May be an acceptable alternative for some

Jehovah’s Witnesses (see Appendix B, pg. 137)

Blood Conservation
• no history of cerebrovascular disease

Complications

!
SAFETY
■ Complications include:
◆ The safety of the procedure is not proven153 A T T E N T I O N
◆ Air embolism – ensure air is removed

prior to re-infusion Air embolism is a risk of


Recommendation intraoperative cell salvage.
◆ Thrombocytopenia and dilutional
■ ANH should NOT be encouraged outside
of a clinical trial setting. coagulopathy
◆ Bacterial contamination (rare)

◆ Tumour dissemination in cancer surgery

INTRAOPERATIVE CELL SALVAGE154 ◆ Hemoglobinemia – ensure correct wash

fluids are used and a formal maintenance


Principles program is performed on equipment
■ A patient’s own blood shed at the time
of an operation is collected in such a way Contraindications
that it can be re-infused into the patient ■ Malignant cells in operative field.
(auto-transfusion). ■ Bacterially-contaminated operative fluid,
■ Up to 80% of red cells can be recovered.155 ascitic fluid, or amniotic fluid in operative field.
■ Use of hypotonic solutions in the operative
field.
■ Use of topical thrombogenic agents in the
operative field.

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Charts
Risk Risk
ERYTHROPOIETIN IN ELECTIVE SURGERY

Paitent
Principles Contraindications (in elective surgery patients)
■ Erythropoietin stimulates erythropoesis ■ Uncontrolled hypertension.
and is produced in response to hypoxia ■ Hypersensitivity to mammalian-derived cell
by the renal cortex. Regulation is by products, albumin, or other components of
classical negative feedback inhibition. the product.
■ Erythropoietin is administered ■ Contraindicated in patients scheduled for
prior to elective surgery to increase elective surgery not undergoing PAD with
hemoglobin and thereby reduce severe coronary, peripheral artery, carotid,
the rate of allogeneic transfusion.158 or cerebrovascular disease, including recent

Transfusion Reactions
◆ Expected rise in hemoglobin is 10-20 g/L MI or stroke.
■ Erythropoietin can be administered to For more details, refer to product monograph.
enhance the collection of autologous
blood (PAD).159,160
◆ Combined use only recommended
Adverse Effects
for patients with very high likelihood ■ Safety of short-term use before surgery
of allogeneic blood exposure and high has not been thoroughly studied.
expected blood loss (e.g., major spine ◆ A recent study found an increased risk
surgery)
of thrombosis in patients undergoing
elective spine surgery.168
For more details, refer to product monograph.
Eligibility

Blood Conservation
■ Patients with a hemoglobin < 130 g/L
and a probability of requiring a blood
transfusion of 10% or greater.158,161,162

Dosage
■ Preferred dose: 600 U/kg sc qwk for up
to 4 doses commencing 28 days before
surgery.163,164,165
◆ e.g., 30,000 or 40,000 U sc qwk x

4 weeks, start 28 days pre-op


■ Alternative dose: 300 U/kg sc qd x
15 days commencing 10 days
preoperative.166
◆ e.g., 20,000 U sc qd x 15 days, start

day 10 pre-op
■ Supplemental iron advised.160,167

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Charts
Risk Risk
ANTIFIBRINOLYTICS

Paitent
General Principles169,170 2. Antifibrinolytics in Non-cardiac Surgery170
■ Antifibrinolytics are administered to prevent/ ■ Used in orthopedic surgery, trauma, and
treat increased fibrinolysis during surgery, hepatic surgery.
particularly cardiac surgery. ■ Preliminary evidence suggests that
■ There are two types of antifibrinolytics: antifibrinolytics reduce allogeneic blood
1. Aprotinin – a proteinase inhibitor derived exposure, but safety has not been fully
from bovine lung that inhibits plasmin assessed.
◆ Currently under a marketing suspension ◆ The most recent meta-analysis included

Transfusion Reactions
due to safety concerns that are being 252 RCTs that recruited over 25,000
reviewed by Health Canada participants
2. Tranexamic acid and aminocaproic acid – ◆ In the tranexamic acid trials, there was

inhibitors of plasminogen a significant reduction in allogeneic


transfusion (RR 0.61, 95% CI 0.53-0.70)
Indications ■ The CRASH-2 study, which included over
1. Antifibrinolytics in Cardiac Surgery 20,000 patients (most from developing
■ Prophylactic administration is preferred countries), provides strong evidence of
rather than at time of marked benefit for low dose tranexamic acid in
hemorrhage. patients with traumatic hemorrhage
■ Tranexamic acid is less potent but has a (dose used: 1 g loading over 10 minutes,
better safety profile than aprotinin.169,170 then infusion of 1 g over 8 hours).172
■ Neither drug has shown to reduce adverse

Blood Conservation
Adverse Effects
event rates outside of bleeding and
■ Aprotinin: hypersensitivity reactions.
transfusions.
◆ Reactions vary from skin flushing to severe
■ As in other drugs, use only when potential
circulatory depression; higher risk on second
benefits outweigh risks.
exposure173
◆ May increase possibility of renal dysfunction
DOSAGE IN CARDIAC SURGERY
in cardiac patients with, or at risk for, renal
Tranexamic 20-100 mg/kg ± 2-4 mg/kg/hr disease
acid for duration of surgery171 ◆ May increase mortality169

■ Tranexamic acid: GI upset, seizures.


◆ Data from meta-analyses do not suggest

an increased risk of thrombosis170

Contraindications174 A T T E N T I O N

!
■ Tranexamic acid – patients at elevated risk Use antifibrinolytics with
of thrombosis, pregnancy, hematuria; dose caution in patients with
adjustment required in renal failure. urinary tract bleeding!
Refer to product monograph for more details. (Clot may cause
ureteric obstruction).

88 89
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Charts
Risk Risk
DDAVP A T T E N T I O N OTHER BLOOD CONSERVATION STRATEGIES

!
■ There is no convincing evidence that DDAVP DDAVP is not indicated as UNDER CLINICAL INVESTIGATION

Paitent
minimizes perioperative allogeneic RBC a routine practice in the The following blood conservation strategies
transfusion in patients who do not have prevention or treatment are under investigation.
congenital bleeding disorders and its of bleeding after
cardiac surgery.
■ There are insufficient data to support the
routine use is not recommended.175,176,177 routine use of these interventions at the
■ There is preliminary evidence that its use current time:
may be beneficial in some patients with ◆ Blood substitutes (hemoglobin-based
acquired bleeding disorders as diagnosed oxygen carriers, human and bovine)
by new point-of-care platelet function
Note: At the present time there are no blood

Transfusion Reactions
devices.177 substitutes licensed for clinical use in Canada.
◆ Recombinant factor VIIa
REGIONAL ANESTHESIA • The effectiveness of rVIIa as a general
■ One systematic review of literature found hemostatic drug, either prophylaxically
that the use of neuroaxial blockage with or therapeutically, remains unclear 183
epidural or spinal anesthesia reduced the ◆ Hypervolemic hemodilution
risk of:178 ◆ Controlled hypotension
◆ transfusion

• risk of transfusion was reduced by 50%


◆ venous thromboembolism
◆ pneumonia and respiratory depression

Blood Conservation
TOPICAL AGENTS 179
■ Fibrin sealants
◆ Mixture of fibrinogen, thrombin, calcium

chloride and anti-fibrinolytic agent (e.g.,


Tisseel)180
◆ Meta-analysis of 18 trials indicates

effectiveness in reducing peri-operative


allogeneic blood transfusion (RR 0.63 95%
CI 0.45-0.88)181
■ Topical thrombin
◆ Bovine thrombin products may induce

immune response
◆ Recombinant human thrombin available

(e.g., Recothrom®)182
◆ No data on effectiveness in reducing

peri-operative allogeneic blood transfusion.

90 91
and Medical Patients
E R Y T H R O P O I E T I N and Medical Patients

Erythropoietin
General Principles184,185 Eligibility
■ Erythropoietin (EPO) is synthesized by DNA ■ Patients with clinically and biochemically
technology: established CRF with a hemoglobin
◆ Some formulations are stabilized with < 90-110 g/L should be considered.190,191
human albumin ■ Usually erythropoietin is considered when the
◆ Formulations without human albumin are creatinine clearance is < 30 mL/min/1.73 m2.
preferred for Jehovah’s Witness patients ■ Other causes of anemia must be excluded or
■ Requires readily available iron for full efficacy. successfully treated:
◆ Initial laboratory work up should include a
■ Takes time to increase hemoglobin (weeks).
CBC, reticulocyte count, serum ferritin, and
■ Erythropoietin response to anemia may be
transferrin saturation
blunted in the presence of malignancy,

Blood Products
chemotherapy, HIV infection, and chronic

Fractionated
Target therapeutic outcome
inflammatory diseases.
■ To maintain the hemoglobin in the range
Contraindications186,187 of 100 to120 g/L.187,192,193
■ Uncontrolled hypertension.
Iron 194
■ Hypersensitivity to mammalian-derived cell
■ Assess iron status every 3 months.
products, albumin, or other components of
the product. ■ Sufficient iron should be administered

■ Who for any reason cannot receive adequate to maintain the serum ferritin > 100 ug/L
antithrombotic treatment. (not on hemodialysis) or > 200 ug/L (on
hemodialysis) AND iron saturation > 20%.
■ Patients scheduled for elective surgery not
■ Intravenous iron is frequently utilized for

Sickle Cell Disease


undergoing PAD, with severe coronary,
peripheral artery, carotid, or cerebrovascular patients who fail oral iron.
disease, including recent MI or stroke. ■ Intravenous or oral iron is acceptable for
CRF patients not on hemodialysis.
Refer to product monograph for more details.
■ Patients should be monitored to prevent
Indications iron overload.
■ Chronic renal failure. ■ Stop iron if ferritin > 500 ug/L.
■ Anemia associated with malignancy. Refer to intravenous iron product monographs for
■ HIV infection. more details.

Dosage
CHRONIC RENAL FAILURE (CRF)188,189 ■ Starting dose: Epoetin alfa187 (Eprex®)
Rationale 300 u/kg subcutaneously (sc) per week or
■ Patients with end-stage renal disease darbepoietin194 (AranespTM) 0.45 ug/kg sc
are unable to produce erythropoietin; per week.
it is administered as a replacement ■ Maintenance dose: adjust dose to maintain
therapy. a hemoglobin level of 100 to 120 g/L.
◆ Adjust dose per product monograph to avoid

major fluctuations in hemoglobin level


■ Where inadequate responses occur,
re-examine for other causes of anemia.

92 93
and Medical Patients
E R Y T H R O P O I E T I N and Medical Patients

Erythropoietin
ANEMIA ASSOCIATED WITH MALIGNANCY HIV INFECTION
Eligibility 195,196 Eligibility
■ Patients with chemotherapy-induced ■ Highly active antiretroviral therapy (HAART)
anemia; AND decreases the incidence of anemia.199
■ Hemoglobin < 100 g/L and/or requiring ■ Erythropoietin was originally indicated for
red cell transfusions patients with anemia taking zidovudine.
◆ Other contributing causes of anemia ■ Similar responses to erythropoietin are
must be excluded or successfully treated obtained in zidovudine- and non-zidovudine-
◆ Carefully weigh the risks of thrombo- treated patients.200,201,202,203
embolism in patients prescribed ■ Erythropoietin significantly decreases the
erythropoietin percentage of patients requiring transfusion

Blood Products
• The relative risk of thromboembolic and reduces the number of units required

Fractionated
complications is increased (RR 1.67, for patients continuing to require
95% CI 1.35-2.06)197 transfusion.
◆ Erythropoietin should not be used in ■ Erythropoietin is unlikely to produce
treatment of anemia associated with a response in patients with serum
malignancy in patients not receiving erythropoietin > 500 u/L.204,205
chemotherapy ■ Other contributing causes of anemia must
• A meta-analysis of 53 studies including be excluded or successfully treated.206
13,933 patients suggested erythropoietin
therapy increases the risk of death compared Target therapeutic outcome
to placebo (Hazards Ratio 1.17, 95% CI ■ To maintain the lowest hemoglobin level
1.06-1.30)198 sufficient to avoid RBC transfusion.

Sickle Cell Disease


• Red blood cell transfusion should be
considered the preferred strategy in patients Therapeutic regimen
undergoing potentially curative treatment ■ Iron supplementation should be used
with caution, as it may be associated
Target outcome with accelerated progression of disease.205
■ To maintain the lowest hemoglobin level ■ Start erythropoietin with a dose of:
sufficient to avoid RBC transfusions. ◆ Eprex 100 U/kg sc 3 times/week;

■ Erythropoietin increases the hemoglobin dose adjust as per package insert


level and decreases the likelihood of
transfusion (RR 0.58-0.67).195

Dosage
■ Iron status should be assessed and iron
deficiency treated.
■ Concurrent iron therapy recommended
unless there are concerns of iron overload.
■ Start erythropoietin with a dose of either:
◆ Eprex 150 U/kg sc 3 times/week or 40,000 U

sc weekly; or Darbepoetin 2.25 ug/kg sc


weekly or 500 ug every 3 weeks sc
■ Adjust dose per product monograph to avoid
major fluctuations in hemoglobin level.
94 95
and Medical Patients
F R A C T I O N AT E D B L O O D P R O D U C T S : A l b u m i n

Erythropoietin
A Basics B Administration & Infusion Practices

■ Albumin is a plasma protein synthesized Dosage

!
by the liver and catabolized by the ■ Caution: Administering 25% albumin A T T E N T I O N
endothelium (daily turnover 9-12 g; in error, instead of 5%, could result Administering 25% albumin
average total body albumin of a 70 kg in severe circulatory overload. instead of 5% in error could

!
patient is 280 g; ~60% interstitial).207 ■ For dosage, see specific indications listed result in circulatory overload!
Manufactured by cold ethanol A T T E N T I O N
■ below.
fractionation from a pool of Albumin is a blood product. ■ Intravascular volume response:
approximately 10,000 blood donors. Consent required.
■ Viral inactivation steps include cold ethanol 500 mL 5% albumin 100 mL 25% albumin*
fractionation, and heat inactivation.

Blood Products
Fractionated
■ In 2009-2010, 6.3 million grams of albumin
were used in Canada, at a cost of about = 25 grams of albumin = 25 grams of albumin
$18.4 million dollars.

500 mL increase 450 mL increase in


ALBUMIN USE KG PER 10,000 PERSONS 208
in intravascular intravascular volume
3 volume (350 mL from
Canada Finland New interstitial pool)
Zealand *25% albumin usually restricted to use in patients with
Scotland Australia
2.5 liver failure

Sickle Cell Disease


Administration 209,210
2 ■ No crossmatch is required.
■ Use regular IV tubing.
■ Fluid compatibility: all IV solutions.
1.5 ■ Record lot number and volume of
albumin administered in patient chart.

1
Adverse reactions /Risks
■ Anaphylaxis – rare.
0.5
■ Circulatory overload.
■ Hypotension – rare case reports of transient
hypotension in patients on angiotensin-
converting enzyme inhibitors.211
0
■ There are no reports of HIV, HCV, or other
1995 1996 1997 1998 1999 2000 2001 2002 2003 2004 2005 2006
viruses transmitted through albumin.

96 97
and Medical Patients
F R A C T I O N AT E D B L O O D P R O D U C T S : A l b u m i n

Erythropoietin
C Indications 2. Spontaneous bacterial peritonitis
■ One RCT (n=126) found that patients
ALBUMIN MAY BENEFIT THE FOLLOWING resuscitated with antibiotics alone
GROUPS OF PATIENTS: compared to antibiotics plus albumin
had a higher mortality (OR 4.5, 95%
1. Paracentesis CI 1.0 to 20.9).218
(According to American Association of the ◆ This study has been criticized for lack

Study of Liver Disease Practice Guidelines 212) of a formalized resuscitation protocol


■ Routine post-paracentesis albumin infusion in the control arm
is expensive and has not been shown to DOSAGE
decrease morbidity and mortality. ■ 25% albumin – 1.5 g per kg within 6 hours
◆ Paracentesis < 5 L – unnecessary of diagnosis and 1.0 g per kg on day 3.

Blood Products
Fractionated
◆ Paracentesis > 5 L – albumin can be ◆ For example: For a 70 kg patient =

considered for patients with refractory 4 x 100 mL of 25% albumin on day 1


cirrhotic ascites with peripheral edema and then 3 x 100 mL of 25% albumin
on maximal diuretic therapy on day 3
VOLUME OF ASCITES # VIALS OF 100 ML 25% ALBUMIN*
<5L 0 3. Hepatorenal syndrome

!
A T T E N T I O N
5-8 L 2
■ Preliminary data suggests that albumin Use of Intravenous
in conjunction with terlipressin219,220,221 or albumin alone is
8-12 L 3 midodrine/octreotide222 may be effective ineffective for
12-15 L 4-5
in salvaging some patients with type 1 hepatorenal syndrome.

Sickle Cell Disease


hepatorenal syndrome who are candidates
* 8 grams albumin per L of fluid removed for paracentesis > 5 L. 213 for liver transplantation.
◆ This therapy has not been shown to
■ One randomized study (n=60) suggests
that starch (20 mL/kg; e.g., 1000-1500 mL change mortality rates in hepato-renal
pentastarch) may be an effective alternative syndrome
◆ Albumin alone, without terlipressin
to albumin.214
■ There is preliminary evidence that or other agent is ineffective
midodrine215 and terlipressin216 may DOSAGE
be alternative therapies to intravenous ■ 100-200 mL of 25% albumin daily with
albumin in this setting. above agents, up to a maximum of

!
■ Malignant ascites – there is no evidence A T T E N T I O N
14 days.220,221,222
to support the use of albumin in patients
with malignant ascites post-paracentesis.217 There is no evidence to
support the use of albumin
in patients with malignant
4. Plasma exchange
ascites post-paracentesis. ■ Currently, the majority of patients
undergoing therapeutic plasma exchange
are replaced with albumin ± crystalloid or
starch, with the exception of patients with
thrombotic thrombocytopenic purpura (TTP)
who are replaced with cryosupernatant or
frozen plasma.

98 99
and Medical Patients
F R A C T I O N AT E D B L O O D P R O D U C T S : A l b u m i n

Erythropoietin
THE CURRENT MEDICAL LITERATURE CAN NOT
CONFIRM ANY BENEFIT OF INTRAVENOUS
ALBUMIN IN THE FOLLOWING SUBGROUPS
OF PATIENTS: 223

1. Resuscitation 3. Severe burns


■ Current evidence: albumin is not ■ 4 small randomized controlled trials with
superior to crystalloid for resuscitation important methodological limitations in
in intensive care. patients with thermal injuries failed to
■ A large randomized controlled trial224 show that 5% albumin was superior to
showed: crystalloids.223,226

Blood Products
◆ No overall advantage of albumin over * O D D S R AT I O ■ There is currently a wide variation in fluid

Fractionated
crystalloid for resuscitation in intensive The odds ratio is a way resuscitation practice in burn patients.227
care of comparing whether ■ Current expert opinion recommends PA R K L A N D F O R M U L A
◆ A non-significant trend to increased the probability of a certain resuscitation with lactated Ringer’s solution Parkland formula =
relative risk of death with albumin event is the same for according to the Parkland formula, with 4 mL/kg/%burn over the
compared with crystalloid in trauma two groups. addition of colloids if the fluid volume first 24 hours, with half of
(OR 1.36, 95% CI 0.99-1.86) An odds ratio of 1 implies exceeds 4 mL/kg/%burn (known as ‘fluid the total fluid given in the
◆ A significantly increased risk of death that the event is equally creep’) and urine output is less than first 8 hours to target urine
in trauma patients with brain injury likely in both groups. 0.5 mL/kg/hour, with hemostatic instability output to 0.5-1.0 mL/kg/hr.
receiving albumin compared with An odds ratio greater after the first 8-24 hours.228,229

!
crystalloid (OR 1.62, 95% CI 1.12-2.34) than 1 implies that the ■ Intravenous albumin should only be A T T E N T I O N
event (e.g., death) is more commenced after transfer to a specialized
◆ A non-significant trend to improved

Sickle Cell Disease


likely in the first group Intravenous albumin should
survival with albumin compared to burn centre.
(here the albumin group). only be commenced after
crystalloid in severe sepsis (OR 0.87, transfer to a specialized
95% CI 0.74-1.02) burn centre.
4. Hypotension during dialysis
■ There are currently no data to support
2. Hypoalbuminemia the use of albumin in the treatment of
■ Current evidence: albumin is NOT superior to hypotension during dialysis.
◆ Small comparison trials of normal saline,
crystalloid for treatment of hypoalbuminemia.
■ One meta-analysis showed a significant albumin (20%), and starch did not suggest
increase in mortality and another showed a superiority of albumin over the other
a non-significant increase in mortality agents 230
◆ A small RCT concluded that 5% albumin
compared to crystalloid:
was no more effective than normal saline
ODDS RATIO (OR)* OR RANGE % INCREASE IN MORTALITY for the treatment of hypotension during
dialysis231
Cochrane Injuries
1.69 1.07-2.67 69% (7 to 167%)
Group 223
Wilkes et al 225 1.59 0.91-2.78 59% (-9 to 178%)

100 101
and Medical Patients
F R A C T I O N AT E D B L O O D P R O D U C T S : A l b u m i n

Erythropoietin
5. Cardiac surgery232
■ There is no evidence to support the use of
albumin, as compared to starch or crystalloid,
for either:
i. Priming fluid for cardiopulmonary bypass
ii. Post-cardiopulmonary bypass

Blood Products
Fractionated
■ There is no evidence from randomized
clinical trials in cardiac surgery patients that
fluid replacement with albumin is associated
with a better pulmonary, cardiac, or renal
outcome.

6. Acute Lung Injury


■ Two small, industry funded randomized
control trials (n=40 233, n=37 234) in
hemodynamically stable patients found

Sickle Cell Disease


the combination of furosemide and
intravenous albumin to result in weight
loss of 10 kg over 5 days, without
improvement in the rate of extubation
success or mortality.

102 103
and Medical Patients
FRACTIONATED BLOOD PRODUCTS: Intravenous Immunoglobulin (IVIG)

Erythropoietin
and Subcutaneous Immunoglobulin (SCIG)

A Basics Cost
■ IVIG costs $60 to $75 per gram
depending on US$ exchange rate.
IVIG is the fraction extracted from donated In 2009-2010
◆ A single course of treatment for a
plasma that contains the immunoglobulins, Canada spent approximately
with > 90% as IgG. 70 kg patient with the commonly
$300 million on IVIG.238
prescribed dose of 1 g/kg each day
for 2 days, costs $8,000-$10,000

Availability & Consumption


■ Approximately 30% of the IVIG used
in Canada is derived from Canadian

Blood Products
plasma,236,238 which is processed separately

Fractionated
!
Products Available 235,236 from other source plasma.
■ Products are supplied by CBS or HQ. A T T E N T I O N ■ The rest is derived from paid U.S. donors.
■ Informed consent is required as for IVIG is a blood product. ■ Canada has the highest per capita
any blood component or product. Consent required. consumptions of IVIG in the world.236
Refer to product’s package insert for further details.
COMPARISON OF IMMUNE GLOBULIN (IVIG AND SCIG) ISSUES IN SELECTED COUNTRIES 238,239
IVIG PRODUCTS LICENSED IN CANADA*
PRODUCT IGIVNEX GAMUNEX PRIVIGEN GAMMAGARD GAMMAGARD VIVAGLOBULIN 140
LIQUID S/D
Manufacturer Talecris Talecris CSL Behring Baxter Baxter CSL Behring 120

Sickle Cell Disease


Corporation Corporation

Grams per 1,000 population


Plasma Canada United United United United United 100
Source States States States States States
80
IgG (g/L) 98 ± 20 100 ± 10 > 90 160
IgA (mg/L) 46 mcg/mL 46 mcg/mL 2.5-12 ≤ 140 ≤ 2.2 Not 60
(average) (average) mcg/mL mcg/mL mcg/mL indicated
(5.6 mcg/mL (in 5% in product
average)237 solution) monograph 40

Sugar Not Not Contains Not 20 mg/mL Not


content specified specified no carbo- specified (2%) specified 20
hydrate glucose
stabilizers (in 5% 0
solution)
any UK nce ly ede
n
stra
lia A nad
a
no sucrose Ge
rm Fra Ita Sw Au US Ca
Osmolality 258 258 320 240-300 Not Not
(mOsmol/kg) indicated indicated IVIG & SCIG issues
in product in product
monograph monograph

Form Liquid Liquid Liquid Liquid Lyophilized Liquid


Route of IV IV/SC IV IV IV SC
admin-
istration

* Consult appropriate package insert for more details, or for information on other products that
may be supplied if licensed products are not available.
104 105
and Medical Patients
FRACTIONATED BLOOD PRODUCTS: Intravenous Immunoglobulin (IVIG)

Erythropoietin
and Subcutaneous Immunoglobulin (SCIG)

GROWTH OF CANADIAN IVIG UTILIZATION (%) Manufacturing


■ IVIG is manufactured from pooled plasma
obtained from several thousand donors
Per cent growth of IVIG utilization (%)

2009-2010 per pool.


■ The constituent plasma units are tested for
2008-2009 human immunodeficiency virus (1 and 2),
hepatitis B, hepatitis C, human T-cell
2007-2008 lymphotropic virus (I and II), and parvovirus B19.
■ The process includes rigorous viral inactivation
2006-2007 steps, e.g., caprylate, low pH, chromatography,
solvent detergent treatment.
2005-2006 ■ There is no evidence of transmission of prion

Blood Products
Fractionated
disease (e.g., variant CJD) through IVIG.
0 2 4 6 8 10
■ Steps in manufacturing are believed to reduce
the risk of transmission of prion disease.240

IVIG UTILIZATION IN CANADA BY PROVINCE/TERRITORY (PER 1,000 POPULATION), 2009-2010


180

160

Sickle Cell Disease


140

120
(grams per 1,000 population)
IVIG Utilization 2009-2010

100

80

60

40

20

0
AB BC MB NB NL NS ON PEI QC SK Territories

106 107
and Medical Patients
FRACTIONATED BLOOD PRODUCTS: Intravenous Immunoglobulin (IVIG)

Erythropoietin
and Subcutaneous Immunoglobulin (SCIG)

B Administration & Infusion Recommendations Adverse reactions


■ In the event of an adverse reaction, stop
Administration the transfusion and assess the patient; if
■ Administer as 5 or 10% solution, usually Dose Calculator
the adverse reaction is minor, the transfusion
dispensed by the hospital blood bank or http://www.transfusion may be continued at a reduced infusion rate.
pharmacy. ontario.org/dose/
■ Report all adverse reactions to your hospital
■ Safe for use in pregnancy. transfusion service.
Refer to package insert for further details.

IVIG INFUSION RATES* ADVERSE REACTIONS TO IVIG 235,241,242,243


PRODUCT INITIAL RATE MAXIMUM RATE COMMENT REACTION SEVERITY FREQUENCY** COMMENT/TREATMENT

Blood Products
IGIVnex 0.6-1.2 mL/kg/hour Increase gradually to Time to infuse 70 g Anxiety, chills/fever, Mild- Common Slow or pause IVIG treatment.

Fractionated
(0.01-0.02 mL/kg/min) a maximum rate of is approximately rash, flushing, moderate Symptomatic treatment. Recurrent
for 30 minutes 3.6 mL/kg/hour if 3 hours headache, chest, back reactions – pre-medicate and/or
or abdominal pain, change to another manufacturer’s
initial dose is tolerated
nausea/vomiting, IVIG product
GAMUNEX™ 0.6-1.2 mL/kg/hour Increase gradually to Time to infuse 70 g tachycardia, hypo-
(0.01-0.02 mL/kg/min) a maximum rate of is approximately or hypertension
for 30 minutes 8.4 mL/kg/hour if 1 3/4 hours Aseptic Meningitis Moderate Rare Stop infusion. Administer analgesics.
initial dose is tolerated Usually resolves spontaneously in
24-48 hours
GAMMAGARD® A 5% solution should be Increase gradually to Use of ante-
used for initial infusion a maximum rate of cubital vein is Anaphylaxis Severe Rare Stop infusion. May require
SD™ epinephrine promptly. Often
at 0.5 mL/kg/hour. If 4 mL/kg/hour if initial recommended,
reaction to IgA in an IgA-deficient
well tolerated, use 10% dose is tolerated especially for

Sickle Cell Disease


patient
solution subsequently 10% solution
at the same rate. Use Acute renal failure Severe Rare Usually with sucrose-containing
(120 cases product (none currently licensed
filter supplied with
reported to in Canada). Predisposing factors:
product FDA in 13 years) age > 65, diabetes mellitus,
GAMMAGARD® 0.5 mL/kg/hour Increase gradually to pre-existing renal insufficiency
Liquid (0.01 mL/Kg/min) a maximum rate of Hemolysis244 Mild- Uncommon More common in non-blood
for 30 minutes 5.0 mL/kg/hour if Severe group O patients
initial dose is tolerated Thrombo-embolic Severe Rare Causative relationship not clearly
Privigen 0.3 mL/kg/hour Increase gradually Product events245 (anecdotal established. Possibly related to
reports) increases in viscosity
(0.005 mL/kg/min) to maximum rate of monograph
2.4-4.8 mL/kg/hour recommends Infectious disease Severe No reported Modern viral reduction measures
(0.04-0.08 mL/kg/min slower rate to be transmission case since HCV are robust. Prion (vCJD) transmission
or 4-8 mg/kg/min) used for patients in 1995.246 No remains an entirely theoretical risk
known case of
with ITP
transmission of
HIV or HBV
* Refer to package insert for further information.
** Reactions are more likely with faster rates of infusion.
Note: IVEEGAM™ is rarely used. For IVEEGAM and unlicensed products, refer to the
package insert.

108 109
and Medical Patients
FRACTIONATED BLOOD PRODUCTS: Intravenous Immunoglobulin (IVIG)

Erythropoietin
and Subcutaneous Immunoglobulin (SCIG)

C Indications IVIG IN SOLID ORGAN TRANSPLANTATION254

DIAGNOSIS EFFICACY/COMMENT DOSE


Immunology
■ There is good evidence to support the Acute antibody mediated rejection in Benefit established 0.1 g/kg/treatment
use of IVIG in congenital and acquired patients who have received living donor/ day or as a set dose
immunoglobulin deficiency, with the deceased kidney donor transplant of 2 g/kg total
following conditions: Steroid-resistant rejection in patients Benefit established. Total dose of
◆ Significant quantitative or functional who have received a living/deceased 2-3.5 g/kg
Consider IVIG to
antibody deficiency that has been donor kidney transplant
improve graft
administered over
established survival when other
a period of up to
◆ Clinical evidence consistent with defective 10 consecutive days
therapies are

Blood Products
humoral immunity (e.g., recurrent infection) unacceptable or

Fractionated
◆ Treatable conditions to which antibody ineffective.
deficiency may be secondary must be Kidney transplant from living donor Possibly effective. 2 g/kg/month
excluded to whom the patient is sensitized (maximum dose
There is uncertainty
◆ Clinical condition severe enough to (HLA or ABO) 180 g) for 4 months
about the best
interfere with the activities of daily living strategy for these
or 0.1 g/kg in
association with
■ Subcutaneous immunoglobulin also available patients.
plasmapheresis in
for home-based immunoglobulin replacement
the perioperative
therapy. Consult a transfusion medicine
period
specialist or immunologist for additional
information.

Sickle Cell Disease


IVIG IN IMMUNOGLOBULIN DEFICIENCY 247,248,249,250

DIAGNOSIS EFFICACY DOSE


Primary immune deficiencies, Benefit established Starting dose of 0.4-0.6 g/kg IV
combined immunodeficiency monthly for three months,
syndromes, IgG subclass depending on the severity of
deficiencies, hyper-IgM deficiency. Dose should then
syndrome be tailored to maintain nadir
of the IgG level above 7 g/L
in most patients. SCIG dosing:
100-150 mg/kg per week.
Acquired hypogamma- Benefit established 0.4 g/kg every three weeks for
globulinemia, e.g., in chronic in adult population. 4-6 months. Dose should then
lymphocytic leukemia,251 be tailored.
Not recommended
multiple myeloma252
for routine use in
pediatric population.
Patients with advanced Benefit established As above
HIV and recurrent serious
infections unresponsive
to antiviral therapy253

110 111
and Medical Patients
FRACTIONATED BLOOD PRODUCTS: Intravenous Immunoglobulin (IVIG)

Erythropoietin
and Subcutaneous Immunoglobulin (SCIG)

Hematology
IVIG IN HEMATOLOGICAL DISORDERS AND
BONE MARROW/STEM CELL TRANSPLANTATION250,255,256,257,258

DIAGNOSIS EFFICACY/COMMENT DOSE DIAGNOSIS EFFICACY/COMMENT DOSE


Idiopathic Thrombocytopenic Purpura Benefit established 1 g/kg for 1-2 days Hemolytic transfusion reaction Not recommended for Not indicated.
(ITP) refractory to standard treatment, (HTR) prophylaxis or routine Determine in
platelet count < 20 x 109/L treatment of HTRs. May consultation.
be of possible benefit in
ITP with persistent or life-threatening Benefit established 1 g/kg for 1-2 days
patients with sickle cell
bleeding and platelet count < 50 x 109/L
disease with serious, life-
Thrombocytopenia associated with Benefit established 1 g/kg for 2 days threatening delayed HTR.

Blood Products
Fractionated
HIV unresponsive to antiviral therapy,
Hemolytic disease of the Not recommended for 0.5 g/kg. Dose
platelet count < 20 x 109/L or < 50 x 109/L
newborn (HDN) use in management of may be repeated
with bleeding
HDN without established in 12 hours.
ITP in pregnancy Appropriate initial 1 g/kg; longest hyperbilirubinemia.
◆ platelet count < 10 x 109/L treatment inter-treatment Recommended if total
◆ platelet count 10-30 x 109/L in interval consistent serum bilirubin is rising
2nd or 3rd trimester with maintaining despite intensive
◆ platelet count < 30 x 109/L and adequate platelet phototherapy or if level
bleeding at any stage in pregnancy count is within 34-51 umol/L
Post-transfusion purpura Anecdotal evidence 1 g/kg for 2 days of the exchange level.260
suggests IVIG is the Rare cases of auto-immune Anecdotal evidence only; 1 g/kg for 2 days

Sickle Cell Disease


preferred treatment hemolytic anemia or neutropenia, consider use only after
Fetal/neonatal allo-immune Considered standard Maternal dose: auto-antibodies to factor VIII or failure of other treatments
thrombocytopenia (F/NAIT) first-line antenatal 1 g/kg weekly. von Willebrand factor, acquired red or in urgent situations
(treatment of mother or fetus)256,259 treatment. Considered Infant: an initial cell aplasia due to parvovirus B19
adjunctive therapy dose of 1 g/kg Allogeneic bone marrow/ No advantage over Not indicated.
Pediatrics for newborn with might provide stem cell transplant261 placebo in HLA-identical Determine in
For infants, review of F/NAIT. Appropriate benefit when sibling donors. Not consultation.
literature suggests IVIG if consultation advisable platelets are recommended for routine
platelets are below 50 x 109/L and with high-risk not available prophylaxis. May be
platelet transfusion if platelets
pregnancy and used for CMV-induced
are below 30 x 109/L (even
neonatal unit. pneumonitis following
without bleeding).
transplantation in
combination with
Pure red cell aplasia (PRCA) Considered first line 0.5 g/kg weekly
ganciclovir.
(viral or immunologic) therapy for PRCA for 4 weeks
associated with Autologous bone marrow/ No benefit Not indicated
parvovirus B19 stem cell transplant 262
occurring in an
immunocompromised
patient. Reasonable
option for
immunologic PRCA
in patients who have
failed other therapies.

112 113
and Medical Patients
FRACTIONATED BLOOD PRODUCTS: Intravenous Immunoglobulin (IVIG)

Erythropoietin
and Subcutaneous Immunoglobulin (SCIG)

Neurology

IVIG IN NEUROLOGICAL DISORDERS*258,263,264

DIAGNOSIS EFFICACY/COMMENT DOSE DIAGNOSIS EFFICACY/COMMENT DOSE


Guillain-Barre Syndrome Benefit established. Recommended Total dose of 2 g/kg Stiff person syndrome Effective in the short-term; Total dose of 2 g/kg
(including Miller-Fisher as treatment option within 2 weeks divided over 2-5 days long-term outcomes unknown divided over 2 days
syndrome and other of symptom onset for patients with (adults) or 2 days
Multiple sclerosis Possible benefit on relapse rate 1 g/kg monthly with
variants) severe and/or progressing symptoms. (children). Evaluate
(relapsing-remitting) but efficacy compared to other or without induction
May be considered as a treatment response at 4 weeks.
agents not known. Option for of 2 g/kg divided
option for relapsed patients who
treatment of patients who fail, over 2-5 days (adults)
initially responded to IVIG.

Blood Products
decline or are not able to take or 2 days (children);

Fractionated
Chronic inflammatory Benefit established; option for short- Total dose of 2 g/kg standard immunomodulatory maintenance
demyelinating term management of new-onset divided over 2-5 days: drug therapies. therapy should
polyradiculopathy CIDP or relapse. Option for long-term maintenance therapy be individualized
therapy in combination with other should be
Epilepsy Ineffective Not indicated
immunosuppressive therapy. individualized
Amyotrophic lateral Ineffective Not indicated
Multifocal motor Benefit established. Recommended Total dose of 2 g/kg
sclerosis (ALS)
neuropathy as first-line therapy. Diagnosis divided over 2-5 days;
should be made by neuromuscular maintenance therapy Acute disseminated Possible benefit. Consider when Total dose of 2 g/kg
specialist. should be individualized encephalomyelitis first-line therapy with high-dose given over 2-5 days
and tailored to the (ADEM) corticosteroids fails or when there (adults) or 2 days
lowest dose that are contraindications to steroid (children)

Sickle Cell Disease


maintains clinical use.
efficacy (usually Alzheimer’s disease Possible benefit. Clinical trials Not currently
1 g/kg or less). are ongoing.265 indicated outside
Myasthenia gravis May be effective in selected 2 g/kg over 2-5 the setting of a
circumstances. Use should be days: maintenance clinical trial
reserved for severe exacerbations therapy should be Opsoclonus-myoclonus Possible treatment option. Total dose of 2 g/kg
or crises. Should not be used as individualized syndrome Objective evidence of clinical given over 2-5 days
maintenance therapy. Appropriate improvement required for (adults) or 2 days
consultation advisable. sustained use. (children)
Lambert-Eaton Option for treatment. Appropriate Total dose of 2 g/kg
Syndrome consultation advisable. divided over 2-5
days: maintenance
therapy should be
individualized

* Other conditions where IVIG is not of proven value include paraprotein polyneuropathy,
neurological vasculitides, paraneoplastic neurological syndromes and autism.

114 115
and Medical Patients
FRACTIONATED BLOOD PRODUCTS: Intravenous Immunoglobulin (IVIG)

Erythropoietin
and Subcutaneous Immunoglobulin (SCIG)

Rheumatology Dermatology

IVIG IN RHEUMATOLOGY258,263 IVIG IN DERMATOLOGY258,274

DIAGNOSIS EFFICACY/COMMENT DOSE DIAGNOSIS EFFICACY/COMMENT DOSE


Dermatomyositis Benefit established. Option Total dose of Toxic epidermal Anecdotal evidence.275 May be 1 g/kg/day for 3 days
in combination with other 2 g/kg divided over necrolysis effective early in clinical course.
agents for patients who have 2-5 days (adults) Case control study did not show
not responded to other or 2 days (children); improvement in outcome.276
immunosuppressive therapies. maintenance
Pemphigus vulgaris Anecdotal evidence 277 supports Total dose of 2 g/kg
Use should be made in therapy should
and variants use of IVIG as adjunctive or second- divided over 2-5
consultation with experts be individualized

Blood Products
line treatment if conventional days. Maintenance

Fractionated
in neuromuscular disease.
treatment is ineffective. treatment should
Polymyositis 264,266 Benefit uncertain; appropriate Determine in be individualized.
consultation advisable consultation
Epidermolysis bullosa Anecdotal evidence 278 supports Total dose of 2 g/kg
Systemic lupus Current evidence does Determine in acquisita use of IVIG as adjunctive or second- divided over 2-5
erythematosus 267,268,269 not support use in routine consultation line treatment if conventional days. Maintenance
management treatment is ineffective. treatment should
be individualized.
Kawasaki disease 270 Benefit established 2 g/kg x 1 day
Bullous pemphigoid Anecdotal evidence 279 supports Total dose of 2 g/kg
Rheumatoid arthritis 267,271 Ineffective Not indicated
use of IVIG as second-line divided over 2-5
Inclusion body myositis 264,272 Ineffective Not indicated treatment if conventional days. Maintenance
treatment is ineffective. treatment should

Sickle Cell Disease


Chronic Fatigue Ineffective Not indicated
be individualized.
Syndrome 273

* For immune thrombocytopenia associated with systemic lupus erythematosus, see Hematology.

116 117
and Medical Patients
FRACTIONATED BLOOD PRODUCTS: Intravenous Immunoglobulin (IVIG)

Erythropoietin
and Subcutaneous Immunoglobulin (SCIG)

Obstetrics and Gynecology Dosing of IVIG for Obese Patients 293 Dose Calculator

The dose of IVIG varies depending on the http://www.transfusion


ontario.org/dose/
IVIG IN OBSTETRICS AND GYNECOLOGY 280 clinical condition. In general, the dose is based
on the patient’s weight. In the case of obese
DIAGNOSIS EFFICACY/COMMENT DOSE patients, the appropriate dosing regimen is
Anti-phospholipid Uncertain benefit 281,282
may Determine in unclear. It is suggested that patients weighing
syndrome improve fetal outcomes when consultation with more than 100 kg and with a body mass index
Aspirin® and heparin have high-risk pregnancy greater than 30 kg/m2 should have their IVIG
been ineffective; appropriate unit and attending dose calculated using an adjusted body weight.
consultation advisable specialist The adjusted weight takes into account the
increased volume of distribution in these
Recurrent spontaneous Ineffective283 Not indicated
patients (because of increased body fluids)

Blood Products
abortion

Fractionated
without accounting for the increase in weight
In Vitro fertilization/ Ineffective284 Not indicated from body fat.
implantation procedures
A tool which assists with the calculation of
the appropriate dose of IVIG based on the
Infectious Diseases patient’s gender, height and weight is available
at www.transfusionontario.org/dose.
IVIG IN BACTERIAL INFECTION 285

DIAGNOSIS EFFICACY/COMMENT DOSE


Septic/Toxic Shock Recommended as an 1 g/kg on day one and

Sickle Cell Disease


Syndrome (Group A adjunctive therapy when 0.5 g/kg on days 2 and
streptococcal sepsis evidence of systemic 3 or 0.15 g/kg per day
with hypotension inflammation and end organ over 5 days
and multi-organ hypoperfusion with fever,
failure) 286,287,288,289 tachycardia, tachypnea and
hypotension

Necrotizing fasciitis 290,291 Possibly recommended for Adjunctive treatment


severe invasive group A in rapidly progressing
streptococcal disease if other disease 1-2 g/kg over
approaches have failed 6 hours
Sepsis in patients in No large randomized controlled Not recommended
critical care 285,286,287,292 trials to confirm benefit for use

■ HIV: see Immunology.


■ Bone marrow transplant and red cell aplasia due
to parvovirus B19: see Hematology.
■ Specific hyper-immune globulins are not discussed.

118 119
and Medical Patients
FRACTIONATED BLOOD PRODUCTS: Prothrombin Complex Concentrates

Erythropoietin
A Basics 294,295 Dose
■ For dosing instructions consult your hospital
policy. In general, a dose of 1000 IU is
Prothrombin complex concentrates (PCCs)
sufficient for patients with weight between
are coagulation factor concentrates that
50-90 kg and INR in the therapeutic range
contain factors II, VII, IX, X. The amount
of the individual coagulation factor levels (< 3).
varies with the specific preparations. ■ The maximum dose should not exceed
3000 IU of Factor IX.
Manufacturing
When
■ The factor concentrate is made from pools
of 1000-2000 plasma donations.
■ Infusion rate should not exceed 2-3 mL/min
for Octaplex® and 8 mL/min for Beriplex®.
■ Plasma units are tested for HIV (1 and 2),

Blood Products
Fractionated
hepatitis B, hepatitis C. Storage
■ Manufacturing processes include viral ■ Store between +2 to +25°C for Octaplex®
inactivation steps. and room temperature (up to 25°C) for
Beriplex®.
Products available ■ Freezing and light exposure may affect
■ PCCs are supplied by CBS and HQ.
product quality.
■ Two prothrombin complex concentrates
are licensed in Canada: Octaplex® and Monitor patient
Beriplex®. ■ Check patient’s vital signs prior to starting,
15 mins. after starting, at end of transfusion
COAGULATION FACTOR LEVELS (IU/ML) IN PCCS 295 and if there are any transfusion reactions.

Sickle Cell Disease


PRODUCT MANU- FACTOR FACTOR FACTOR FACTOR PROTEIN PROTEIN AT III HEPARIN ■ Repeat INR immediately postinfusion
FACTURER II VII IX X C S to ensure adequate correction of INR.
Octaplex® Octa- 31.4 16.1 22.3 24.4 12.0 22.2 0.1 6.0 ■ Effective half life of PCC is approximately
pharma 6 hours.
Beriplex® CSL 31.0 16.2 28.9 41.3 17.9 21.6 0.6 0.5
Behring INDICATIONS FOR PCCS
PCCs should
1. For patients on warfarin or vitamin K not be given
deficiency with INR values > 1.5 AND to correct
a) life or limb threatening bleeding; or coagulopathies
B Monitoring & Infusion Practices for Octaplex® and Beriplex® 294,296
b) emergency surgery required within 6 hours other than warfarin.
2. PCCs should NOT be administered if: If PCCs not effective in
How reversing warfarin, then
◆ INR ≤ 1.5 as individual coagulation factors
■ Lyophilized powder must be reconstituted other etiologies should
for administration. are not below the level needed to maintain
be considered.
hemostasis
■ Final volume is 20 mLs per vial which
◆ Patients with coagulopathies not related
contains 500 IU of factor IX.
to warfarin or Vitamin K deficiency as
■ Can be prepared in syringe or minibag for
A T T E N T I O N they are deficient in coagulation factors
intravenous infusion.

!
Vitamin K should be given not contained in PCCs
■ Vitamin K 5-10 mg IV (not intramuscular ◆ Patients with known HIT (Beriplex® and
intravenously at same time
or subcutaneously) should be administered Octaplex® both contain heparin)
as PCCs to avoid rebound
immediately to avoid rebound anticoagulation. ◆ Patient has received or will receive
anticoagulation.
recombinant Factor VIIa
120 121
and Medical Patients
S I C K L E C E L L D I S E A S E

Erythropoietin
A Principles of Transfusion in Sickle Cell Disease Phenotypically-matched RBCs A T T E N T I O N

!
■ Determine extended phenotype (Rh, Kell, Life-saving transfusion
Patients with sickle cell disease: A T T E N T I O N
Duffy, Kidd and MNS blood groups) at first should not be withheld

!
visit. if prophylactically
■ Have elevated blood viscosity which may Indications for transfusion
■ In patients with no previous alloantibodies, phenotype-matched RBCs
be exacerbated by increases in hematocrit. in patients with sickle cell are not available.
disease differ significantly
select RBCs matched for the patient’s Rh
■ Are more likely to experience delayed
from other patients. (D,C,c,E,e) and Kell (K1) antigens.
hemolytic transfusion reactions. Hence the
indications for transfusion in patients with
■ If known alloantibodies, select RBCs that are
sickle cell disease differ significantly from matched for the patient’s Rh (D, C, c, E, e),
other patients: Kell (K1), Kidd (Jka, Jkb), Duffy (Fya) and S
A T T E N T I O N (S,s) antigens, as well as any antigens to
◆ Exacerbation of anemia: in the absence

!
which the patient is immunized.300

Blood Products
of heart failure, dyspnea, hypotension In the absence of symptoms,

Fractionated
transfusion should be avoided ◆ Matching for Fyb in sickle cell patients with
or marked fatigue, transfusion should
be avoided unless the hemoglobin has unless the hemoglobin has the Fy(a-b-) phenotype is rarely necessary
decreased to < 50 g/L.297 decreased to < 50 g/L. ■ If there is not sufficient time or resources to
• A rapid decrease in Hgb can be anticipated determine the patient’s phenotype, contact
if the reticulocyte count falls below other hospitals that may have transfused
250 x 109/L the patient previously. (In some regions of
Canada, CBS maintains a phenotype registry
◆ Treatment or prevention of sickle cell
of patients with sickle cell disease.)
complications: total hemoglobin (Hgb)
should not be increased above 100- Leukoreduced blood products
110 g/L.298 ■ As patients with sickle cell disease are at

!
• Augmentation of oxygen delivery in

Sickle Cell Disease


A T T E N T I O N higher risk of harm from the effects of
patients with sickle cell disease is achieved non-leukoreduced RBCs (febrile transfusion
Never transfuse a sickle cell
more efficiently through decreasing the patient to a hemoglobin reactions, transmission of certain viruses
HgbS% than by increasing the total Hgb > 100-110 g/L. and bacteria, alloimmunization to RBC,
level 299 HLA and HPA antigens), only leukoreduced
RBCs and platelets should be selected.301
◆ As of 1999, all blood products in Canada

B Special Transfusion Requirements are pre-storage leukoreduced

Sickledex®-negative blood
■ The following apply to patients with ■ RBC units which test positive by Sickledex®
HgbSS, HgbSß-thalassemia or HgbSC.
test are from donors with sickle cell trait
No special precautions are required for
(HgbSA). This blood is therefore safe to
patients with HgbSA (sickle cell trait).

!
administer to patients with sickle cell
■ Notify the hospital’s Blood Transfusion A T T E N T I O N disease, but it will confound post-transfusion
Service whenever a patient with sickle measurements of the patient’s HgbS%
cell disease presents, to allow sufficient Notify blood bank
immediately. and should be avoided, if possible.301
time to prepare specialized blood products
should the need for transfusion arise.

122 123
and Medical Patients
S I C K L E C E L L D I S E A S E

Erythropoietin
C Exchange Transfusion D Transfusion Indications (first line)

■ Depending upon a patient’s initial Hgb, it THERAPEUTIC TRANSFUSION


may not be possible to achieve a specific
target HgbS% by top-up transfusion without Aplastic Crisis
exceeding a total Hgb of 100-110 g/L. ■ Most commonly due to parvovirus B19
■ Exchange transfusion may therefore be infection, with profound reticulocytopenia
required for the traditional HgbS% goal following a viral illness.
of < 30% (HgbA% > 70%). ■ Due to decreased lifespan of sickle RBCs
■ Ensure patient is euvolemic before initiating (16-20 days), significant fall in Hgb will
an exchange. occur before the reticulocyte count
recovers.302

Blood Products
Fractionated
Manual/partial exchange: ■ Transfusion support may be required if
■ A typical protocol (for children, smaller symptomatic anemia, or if Hgb < 50 g/L.
comparable volumes, e.g., 10 mL/kg):298 ■ Due to a compensatory increase in plasma
1. Phlebotomize 1st 500 mL of whole blood volume, transfuse slowly to avoid volume
(for patients who are very anemic at overload and consider pre-transfusion
baseline [e.g., Hgb < 70 g/L], a top-up diuretic.
transfusion may be required before first
phlebotomy) Sequestration crisis
2. Bolus 500 mL of 0.9% normal saline ■ Trapping of sickle erythrocytes in splenic
3. Phlebotomize 2nd 500 mL of whole blood sinusoids resulting in massive, painful
enlargement of spleen and severe anemia
4. Transfuse 2 units of RBCs

Sickle Cell Disease


over a period of hours.
5. Repeat as necessary to achieve target ■ If untreated, sequestration crises cause
HgbS% (typically a 1.5 blood volume death from hypovolemic shock/anemia;
exchange is necessary for first treatment; immediate transfusion often required.
single cycles may be adequate for
maintenance therapy). Note that for
■ Post-transfusion hemoglobin levels
patients starting with Hgb near 100 g/L, often higher than expected, suggesting
step 4 should alternate between autotransfusion as sequestered RBCs
transfusion of 1 and 2 units in order to released back into circulation.
keep total Hgb from exceeding 110 g/L ■ To avoid accidental polycythemia and
hyperviscosity, transfuse 1 unit at a time,
Automated exchange/erythrocytopharesis reassessing Hgb level before administering
■ Small aliquots of whole blood withdrawn more.
under pressure, RBCs separated by
centrifugation and discarded, plasma and Pediatrics
platelets returned to patient accompanied by In children, consider administering
donor RBCs (usually through separate line). RBCs in smaller than normal
■ Cycle repeats until goal Hgb and HgbS% aliquots (e.g., 3-5 mL/kg). Often a single
achieved. transfusion is sufficient to reverse a
■ Automated exchanges are faster and more sequestration crisis.303
precise than manual exchanges but require
specialized equipment and trained
personnel.

124 125
and Medical Patients
S I C K L E C E L L D I S E A S E

Erythropoietin
Progressive cholestasis
■ Less commonly, patients may present with ■ Syndrome that may occur in absence of
hepatic sequestration crises, characterized by cirrhosis, marked by right upper quadrant
a rapidly enlarging liver accompanied by a pain, extreme elevation of bilirubin and
decrease in hemoglobin, a rise in reticulocyte alkaline phosphatase, and variable elevation
count, and a conjugated hyperbilirubinemia. in transaminases.
◆ Transfusions should also be administered ◆ May be accompanied by renal failure,

cautiously due to the risk of autotransfusion thrombocytopenia, and prolonged


and hyperviscosity. Recurrences are coagulation times
common 297 ◆ All survivors have been treated with RBC

exchange transfusion 297


Acute chest syndrome
Acute chest syndrome ■ In contrast, benign cholestasis

Blood Products
■ A new infiltrate on CXR in a patient with

Fractionated
with the following (unaccompanied by fever, abdominal pain,
sickle cell disease, associated with one or suggest need for gastrointestinal symptoms, or hepatic
more symptoms of fever, cough, sputum exchange transfusion synthetic failure) resolves within months
production, tachypnea, dyspnea, or new- rather than top-up without specific therapy.297
onset hypoxia. transfusion:
■ May progress rapidly to respiratory failure ◆ Altered mental status Acute ischemic stroke or retinal artery
and be complicated by neurologic events.304 ◆ Persistent HR > 125 occlusion
■ May be triggered by infection or marrow bpm, RR > 30/min, ■ Transfusion recommended for adult patients
embolism as complication of vaso-occlusive temp > 40°C, or without other obvious stroke etiology
pain episode; specific cause not identified hypotension (e.g., cardioembolism).303
in ~60% of cases.304 ◆ Arterial pH < 7.35;
Empiric treatment with bronchodilators, SpO2% < 88%

Sickle Cell Disease



Pediatrics
incentive spirometry and antibiotics (e.g., despite aggressive
ventilatory support
Transfusion recommended for all
macrolide or quinolone) advisable in all pediatric patients. Within 3 hours
patients. ◆ Serial decline in
of the first unit of transfused RBCs,
■ RBC transfusion in setting of acute SpO2% or A-a
MCA flow velocity decreases by 20%.308
chest syndrome results in improved gradient
Exchange transfusion associated with
oxygenation.304 Some studies have observed ◆ Fall in Hgb > 20 g/L lower recurrence rate than top-up
equivalent outcomes whether patients ◆ Platelet count transfusion.309
treated with exchange transfusion (HgbS% < 200/fL x 109/L
Note: Most strokes in young adult patients with
goal of 30%) or top-up transfusion (Hgb ◆ Elevated troponin or sickle cell disease are hemorrhagic for which the
goal of 100 g/L).304,305 However, other brain natriuretic role of transfusion therapy remains unclear.310
studies suggest that patients receiving peptide (BNP)
top-up transfusions may progress to ◆ Evidence of
requiring exchange.306 multiorgan failure
■ In absence of evidence from randomized (e.g., renal or hepatic
controlled trials, most patients with acute dysfunction)
chest syndrome should be transfused, with ◆ Pleural effusions
exchange transfusions reserved for patients or progressive
with more severe or rapidly progressing pulmonary infiltrates
disease 307 with concerning symptoms
(see yellow box to the right).

126 127
and Medical Patients
S I C K L E C E L L D I S E A S E

Erythropoietin
PROPHYLACTIC
Perioperative
■ Due to high rates of perioperative ■ Pre-operative transfusion support requires SURGICAL
complications (e.g., 10% rate of acute chest assessment of both surgical and patient risk: PROCEDURE
syndrome), aggressive supportive care and ◆ Low-risk procedures (e.g., skin, ENT, dental,
Low-risk: skin, ENT,
close observation is indicated for all patients perineal, inguinal or distal extremity dental, perineal,
with sickle cell disease undergoing surgical surgery): transfusion likely not required 303,313 inguinal or distal
procedures.311,312 ◆ Intermediate-risk procedures (e.g., extremity surgery
◆ Avoid surgery during vaso-occlusive episodes
abdominal or orthopedic surgery): pre-op Intermediate-risk:
◆ Assure ≥ 8 hrs pre-procedure hydration transfusion advised on basis of observational abdominal or
(admission to hospital 12-24 hours studies.314 A large randomized controlled orthopedic surgery

Blood Products
pre-operatively and monitoring for trial311 has demonstrated that top-up

Fractionated
48 hours post-operatively should be transfusion to Hgb 100 g/L (approx. High-risk: intracranial,
considered) HgbS% of 60%) is equivalent to exchange cardiovascular, or
transfusion (HgbS% goal of 30%) in intrathoracic procedures;
◆ Avoid hypothermia
pars plana vitrectomy or
◆ Avoid use of tourniquets
preventing post-operative complications,
scleral buckling
and decreases transfusion-related adverse
◆ Favour laparoscopic approaches
events
◆ Post-operative prophylaxis for deep
◆ High-risk procedures (e.g., intracranial,
venous thrombosis cardiovascular, or intrathoracic procedures;
◆ Periprocedure incentive spirometry pars plana vitrectomy or scleral buckling)
◆ Aggressive control of pain or intermediate-risk procedures in patients
◆ Early remobilization with significant comorbidities (e.g., chronic

Sickle Cell Disease


pulmonary disease): although little
supporting data, exchange transfusion
(HgbS% goal of 30%) should be
considered 313,315
◆ Exchange transfusion should also be

considered for patients undergoing


intermediate risk procedures whose
Hgb level is ~100 g/L at baseline

128 129
and Medical Patients
S I C K L E C E L L D I S E A S E

Erythropoietin
E Transfusion Indications (second line)

High Stroke Risk Initial therapeutic goal for the following


■ In children, transfusion indicated for indications should be HgbS% < 30% by
secondary prevention of ischemic stroke exchange transfusion. Several months after
and for primary prevention in patients condition stabilizes, may attempt gradual
with high-risk features (e.g., high middle transition to higher HgbS% target by either
cerebral artery or internal carotid blood decreasing quantity of RBCs transfused, or
flow by pediatric transcranial ultrasound). increasing interval between transfusion.
◆ In the latter group, maintaining HgbS < 30%

while keeping total Hgb < 120 g/L results in 1. Recurrent pain episodes/acute chest
a 92% reduction in stroke incidence 316 syndrome

Blood Products
In patients who have failed an adequate

Fractionated

■ Transfusions should be continued indefinitely
trial of hydroxyurea, chronic transfusion
as discontinuation is associated with high
support may be considered as means of
risk of stroke recurrence.317
decreasing recurrence of vaso-occlusive
◆ It is likely safe to relax HgbS% goal to
pain episodes or acute chest
50% for patients who have been free syndrome.320,321
of neurologic events after 3-5 years of ■ Transfusion not indicated as treatment
transfusion support 318
of uncomplicated acute vaso-occlusive
■ Little evidence to guide initiation of pain episodes, or for treatment of chronic
transfusions for stroke prophylaxis in adults, pain syndromes (e.g., avascular necrosis,
or following primary hemorrhagic strokes. osteomyelitis, neuropathic pain).303,322
◆ The underlying pathophysiology for both

Sickle Cell Disease


A T T E N T I O N
thrombotic and hemorrhagic strokes in 2. Priapism
Be vigilant for ASPEN
sickle cell disease is likely the same 319 ■ Transfusion may be of benefit for
syndrome (Association
episodes lasting > 4 hours, unresponsive of Sickle Cell Disease,
to aspiration of blood from the corpora Priapism, Exchange
cavernosa and irrigation with dilute Transfusion, and Neurologic
epinephrine.323,324 events).325

3. Malleolar ulcers
■ Transfusion may speed healing if no
response to bed rest, wound care,
antibiotics, hyperbaric oxygen.326

130 131
and Medical Patients
S I C K L E C E L L D I S E A S E

Erythropoietin
F Transfusion Complications

4. Pregnancy Delayed hemolytic transfusion reactions


■ Transfusion not of benefit for uncomplicated ■ Without prophylactic phenotypic matching,
pregnancy if adequate pre-natal care 30% of transfused patients with sickle cell
provided (e.g., bi-weekly obstetrics disease will develop alloantibodies, two
assessment, weekly in last month).321 thirds of them directed towards C, E and
■ Transfusion support may be considered K1 antigens.329
for pregnant patients with:303 ◆ Alloimmunization due in part to genetic

◆ Significant comorbidities differences in the antigens expressed on


◆ Chronic renal, pulmonary or hepatic disease
red blood cells in the donor population
(primarily Caucasians) and recipients

Blood Products
!
◆ History of recurrent fetal loss

Fractionated
■ 30-50% of antibodies will be undetectable A T T E N T I O N
◆ Multigestational pregnancy or evidence of
on retesting within the year; patients
chronic fetal distress/intrauterine growth Alloimmunized sickle
may be inadvertently re-challenged with
retardation cell patients require
subsequent transfusions, resulting in high antibody card.
rate of delayed hemolytic transfusion
5. Pulmonary hypertension
reactions.301
■ Confirm pulmonary arterial hypertension by
right-heart catheterization in patients with
■ Prophylactic matching for antigens
tricuspid regurgitant jet > 2.5 m/s or RVSP therefore advised when selecting RBCs for
> 30 mmHg on echocardiogram. sickle cell patients; advance notification of
blood bank required.
■ Consider transfusion therapy if no response
to, or intolerance of, hydroxyurea or
■ Delayed hemolysis manifests 1 week to

Sickle Cell Disease


vasodilators (e.g., inhaled nitric oxide).327 1 month after transfusion by worsening
of hemolytic indices (increased indirect
bilirubin and lactate dehydrogenase)
Note: Priapism, pulmonary hypertension and malleolar accompanied by new alloantibody in
ulcers may represent complications of chronic patient plasma (detected by blood group
intravascular hemolysis (e.g., nitric oxide depletion)
rather than acute vaso-occlusion.328
and screen) and/or on patient’s RBCs
(detected by direct antiglobulin test).
■ Patients often present with symptoms
typical of a vaso-occlusive pain episode. In
some cases, delayed hemolytic transfusion
reactions may progress to hyperhemolysis
(see next section).

132 133
and Medical Patients
S I C K L E C E L L D I S E A S E

Erythropoietin
Hyperhemolysis Transfusional iron overload Iron

■ Defined as post-transfusion RBC destruction ■ Each transfused unit of RBCs delivers


accompanied by fall in Hgb to below 200 mg of iron. Red Blood
Cells =
pre-transfusion levels. ■ Significant iron overload therefore likely
◆ Hemolytic indices increased from baseline, after repeated top-up transfusions: may
200 mg
occasionally accompanied by relative eventually result in hepatic, cardiac or
reticulocytopenia 330 endocrine dysfunction.
◆ Acute: occurs less than 7 days after ■ Selecting fresh RBCs (< 7 days old) may
transfusion, often with no new antibodies slow iron loading in chronically transfused

Blood Products
detectable patients to a small degree.

Fractionated
◆ Delayed: occurs between 1 and 4 weeks ■ Exchange transfusions can more effectively
following transfusion and often mitigate or even reverse iron loading.333
accompanied by new RBC antibodies ■ Iron chelation therapy indicated once
■ Enhanced hemolysis appears to involve both hepatic iron concentration > 7 mg/g dry
transfused and autologous RBCs, and may be weight, as assessed by either biopsy or
exacerbated by further transfusion of even calibrated MRI scan.334
crossmatch compatible/antigen-negative ◆ This degree of iron loading can be
RBCs. anticipated after the transfusion of more
■ Avoid further transfusions, if at all possible: than 100 mg/kg of iron (in adult patients,
◆ Treat with IVIG 2 g/kg over 2-5 days approximately 20-30 RBC units)

Sickle Cell Disease


◆ Accompany by high dose steroids ◆ Iron overload correlates poorly with serum

(e.g., prednisolone 1 mg/kg/d x 7 days) ferritin in sickle cell patients but is likely
◆ Consider brief course of erythropoietin
present if serum ferritin persistently
if relative reticulocytopenia 331 > 3000 ng/mL 335
■ Iron chelators licensed for use in Canada
Hyperviscosity include deferoxamine and deferasirox
■ Sudden onset hypertension during or (deferiprone also available through Health
shortly after transfusion, accompanied Canada’s Special Access Program).
by signs of congestive heart failure and ◆ Referral to a centre with expertise in iron

profound alterations in mental status, chelation therapy advised prior to initiation


including stupor, coma, seizures, or features of treatment
of intra-cerebral infarct or hemorrhage.332

!
■ Risk increases if Hgb transfused above A T T E N T I O N
100-110 g/L in patients with SCD and
HgbS% > 25%, particularly if patient Never transfuse
dehydrated and hypoxemic.299 a sickle cell patient
> 100-110 g/L
◆ May also occur secondary to auto-

transfusion following transfusion


support of sequestration crises
■ Manage with emergency phlebotomy.

134 135
A P P E N D I C E S

Appendices
Appendix A Appendix B
Price List Information for Physicians Treating Patients Who Are Jehovah’s Witnesses
ITEM PRICE Jehovah’s Witnesses refuse Witness patients will accept most
transfusion of allogeneic blood surgical and anesthesiological
Red blood cells* $419
based on their understanding procedures (e.g., hemostatic
Autologous (whole) blood $419 of several Biblical passages, surgical instruments, hypotensive
4 units buffy coat derived platelets $286 which they view as prohibiting anesthesia), most diagnostic
the use of: and therapeutic procedures (e.g.,
1 unit single donor (apheresis) platelets $619 phlebotomy for laboratory testing,
• Whole blood, including
1 unit HLA-matched single donor (apheresis) platelets $1,250
predonated autologous
angiographic embolization),
Apheresis fresh frozen plasma $360 blood (predeposit)
pharmacologic agents to enhance
hemostasis (e.g., topical and
4 units frozen plasma $156 • Red blood cells systemic hemostatic agents) and
8 units cryoprecipitate $1,080 • White blood cells therapeutic agents to stimulate
Tranexamic acid 6 g $247.20 • Platelets hematopoiesis (including
• Plasma recombinant products) that do
IVIG per gram $63 not contain blood derivatives,
Albumin 5% 500 mL $65 synthetic oxygen therapeutics,
Their religious understanding and non-blood volume expanders.
Pentaspan® per 500 mL $55 may permit the use of products
Voluven® per 500 mL $55 containing fractions of plasma A valuable and detailed discussion
or cellular components, such as: of the position of Jehovah’s
Blood group (ABO, Rh D) $10
Witnesses on blood transfusion
Antibody screen $30 • Cryoprecipitate and related interventions is
Crossmatch (no antibody) $12 • Clotting factor concentrates available.337
• Albumin Physicians should discuss the
Crossmatch (antibody positive patient) $30
• Intravenous immunoglobulin options with individual patients
Octaplex® 1,000 IU $720
• Fibrin glue because each person must make
Recominant Factor VIIa/mg $1,163 personal decisions according
• Hemoglobin-based oxygen
Anti-D 120 mcg $33 carriers to their conscience regarding
the acceptance of blood
Anti-D 300 mcg $82 • Recombinant factor VIIa
derivatives and autologous
• Autologous blood obtained blood management options.
* This cost refers only to the acquisition cost of a unit of RBC. The cost of delivery of a by acute normovolemic
unit of blood to a patient ranges from $522 to $1183 (US). 336 Jehovah’s Witnesses have
hemodilution or by cell salvage
established a network of Hospital
Liaison Committees (HLC) across
Canada. On call local HLC
members can be contacted
through the hospital switchboard
or by contacting the Hospital
Information Services for Jehovah’s
Witnesses. This service is available
24 hours a day at 1-800-265-0327.

136 137
A P P E N D I C E S

Appendices
Appendix C
Original Advisory Panels for Bloody Easy, Version 1

BLOOD PRODUCTS ADVISORY PANEL BLOOD CONSERVATION ADVISORY PANEL


Dr S A McCluskey, UNIVERSITY HEALTH NETWORK, TORONTO – CHAIR Dr K Karkouti, UNIVERSITY HEALTH NETWORK, TORONTO – CHAIR
Dr R Arrelano, QUEEN ELIZABETH II HSC, HALIFAX Dr G Batnagar, TRILLIUM HEALTH CENTRE, MISSISSAUGA
Dr M Chapman, SUNNYBROOK & WOMEN’S HSC, TORONTO Dr G Bryson, OTTAWA HOSPITAL, OTTAWA
Dr D Cheng, UNIVERSITY OF WESTERN ONTARIO, LONDON Dr L Burry, MOUNT SINAI HOSPITAL, TORONTO
Mr A Coovadia, SUNNYBROOK & WOMEN’S HSC, TORONTO Dr M Clairoux, CENTRE HOSP. UNIV. DE SHERBROOKE, HOPITAL FLEURIMONT
Dr C Cruise, TRILLIUM HEALTH CENTRE, TORONTO Dr N Colterjohn, HAMILTON HEALTH SCIENCES CORP., HAMILTON
Dr D Fergusson, OTTAWA HEALTH RESEARCH INSTITUTE, OTTAWA Ms L Evans, UNIVERSITY HEALTH NETWORK, TORONTO
Dr I Fleming, UNIVERSITY HEALTH NETWORK-MOUNT SINAI, TORONTO Dr B Feagan, LONDON HEALTH SCIENCES CENTRE, LONDON
Dr B Hannach, CANADIAN BLOOD SERVICES, TORONTO Ms K Luke, ST MICHAEL’S HOSPITAL, TORONTO
Dr G Hare, ST MICHAEL’S HOSPITAL, TORONTO Dr D Mazer, ST MICHAEL’S HOSPITAL, TORONTO
Dr H Hume, CANADIAN BLOOD SERVICES, OTTAWA Dr S A McCluskey, UNIVERSITY HEALTH NETWORK, TORONTO
Dr R McLean, HAMILTON HEALTH SCIENCES CORP., HAMILTON Dr B Muirhead, WINNIPEG HEALTH SCIENCES CENTRE, WINNIPEG
Dr B McDonald, OTTAWA HOSPITAL, OTTAWA Dr J Murnaghan, SUNNYBROOK AND WOMEN’S COLLEGE HSC, TORONTO
Dr T M Yau, UNIVERSITY HEALTH NETWORK, TORONTO Dr M Oliver, SUNNYBROOK AND WOMEN’S COLLEGE HSC, TORONTO
Dr G Piliotis, TORONTO-SUNNYBROOK REGIONAL CANCER CENTRE, TORONTO
Dr D Towns, CANADIAN BLOOD SERVICES, CALGARY
TRANSFUSION REACTIONS ADVISORY PANEL
Dr M A Blajchman, HAMILTON HEALTH SCIENCES CORP., HAMILTON – CHAIR
Dr R M Barr, LONDON HEALTH SCIENCES CENTRE, LONDON FRACTIONATED BLOOD PRODUCTS ADVISORY PANEL
Dr G Clarke, CANADIAN BLOOD SERVICES, EDMONTON
IVIG
Ms J DiTomasso, MCMASTER UNIVERSITY, HAMILTON
Dr G A Rock, OTTAWA HOSPITAL, OTTAWA – CHAIR
Dr J Freedman, ST MICHAEL’S HOSPITAL, TORONTO
Dr V Bril, UNIVERSITY HEALTH NETWORK, TORONTO
Ms N Heddle, MCMASTER UNIVERSITY, HAMILTON
Dr D Lane, CANADIAN BLOOD SERVICES, WINNIPEG
Dr S Kleinman, UNIVERSITY OF BRITISH COLUMBIA, VICTORIA
Dr C Laskin, UNIVERSITY HEALTH NETWORK, TORONTO
Ms R Koen, ST MICHAEL’S HOSPITAL, TORONTO
Ms A Lima, SUNNYBROOK AND WOMEN’S HSC, TORONTO
Dr D H Lee, QUEEN’S UNIVERSITY, KINGSTON
Dr A McGeer, MOUNT SINAI HOSPITAL, TORONTO
Ms A Lima, SUNNYBROOK AND WOMEN’S HSC, TORONTO
Dr M Nicolle, LONDON HEALTH SCIENCES CENTRE, LONDON
Ms S McMillan, NIAGARA HEALTH SYSTEM, ST CATHARINES
Dr L Rubin, ST MICHAEL’S HOSPITAL, TORONTO
Dr N Shear, SUNNYBROOK AND WOMEN’S HSC, TORONTO
Dr D Sutton, UNIVERSITY HEALTH NETWORK, TORONTO
Dr A Tinmouth, OTTAWA HOSPITAL, OTTAWA
Dr I Walker, HAMILTON HEALTH SCIENCES CORP., HAMILTON
Dr K Webert, MCMASTER UNIVERSITY, HAMILTON
ALBUMIN
Dr N Baig, TRILLIUM HEALTH CENTRE, MISSISSAUGA
Dr C Bell, ST MICHAEL’S HOSPITAL TORONTO
Dr A Cooper, SUNNYBROOK AND WOMEN’S HSC, TORONTO
Dr R Fowler, SUNNYBROOK AND WOMEN’S HSC, TORONTO
Dr D Irwin, UNIVERSITY OF TORONTO, TORONTO
Dr W Sibbald, SUNNYBROOK AND WOMEN’S HSC, TORONTO
Dr S Tobe, SUNNYBROOK AND WOMEN’S HSC, TORONTO
Dr F Wong, UNIVERSITY HEALTH NETWORK, TORONTO

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