Massive Transfusion And

Coagulopathy

Christine Mai, MD
Faculty Advisor: Mauricio Gonzalez, MD
Department of Anesthesiology
Boston University Medical Center

Guidelines to Blood Product

Transfusions

In 1994, the ASA established the Task Force on Blood

Component Therapy to develop evidence-based
guidelines for transfusing blood products in
perioperative and peripartum settings
22 million blood components transfused yearly
Benefits: improved tissue oxygenation and decreased
bleeding
Risks: Transmission of infectious diseases, hemolytic
and nonhemolytic transfusion reactions,
immunosuppression, alloimmunization, coagulopathy

Massive Transfusion
American Association
of Blood Banks
definition: replacement
of one blood volume
(equivalent to 10 units
of blood) in any 24 hr
period, or half of the
blood volume (5 units
of blood) in any fourhour period

American College of Surgeons Classes of Acute Hemorrhage

Class

II

III

IV

Blood loss (ml)

750

750-1500

1500-2000

2000

Blood loss (%
blood volume)

15%

15-30%

30-40%

40%

Pulse rate

<100

>100

>120

140

Blood pressure

Normal

Normal

Decreased

Decreased

Pulse pressure
(mmHg)

Normal or
increased

Decreased

Decreased

Decreased

Capillary refill
test

Normal

Positive

Positive

Positive

Respiratory rate

14-20

20-30

30-40

>35

Urine output
(ml/hr)

30

20-30

5-15

Negligible

CNS-mental
status

Slightly anxious

Mildly anxious

Anxious and
confused

Confused,
lethargic

Crystalloid

Crystalloid

Crystalloid +
Blood

Crystalloid +
Blood

Fluid replacement
(3:1 rule)

Parameters For Fluid Replacement

Maintenance
Deficits
Insensible loss
Estimated blood loss

Maintenance

4:2:1 Rule or Calculate Wt +40 cc

Calculated weight: (IBW + ABW)/2
IBW male: 110 lbs + 7 lbs * in > 5
female: 100 lbs + 6 lbs * in > 5

Deficits

NPO status
Calculated Wt x hrs NPO x 0.7
Bowel prep ~ 1200cc
Diuretics/ Urine output
NGT drainage
CT drainage

Insensible Loss
Case Type
Volume
Non-open
2-3 cc/kg/hr
Open
4-6 cc/kg/hr
Major Abdominal
6-10 cc/kg/hr
Trauma
> 10 cc/kg/hr
(Volume based on Calculated Weight)

Estimated Blood Loss

The 3: 1 Rule, replace 3 cc crystalloid : 1 cc

blood loss
The 1:1 Rule, replace 1 cc colloid : 1 cc
blood loss

Allowable Blood Loss

(Hct present - Hct allowable) + EBV
Hct present

Estimated Blood Volume

Adults: 75 cc/kg
Infants: 80 cc/kg
Neonates: 85cc/kg

Fluid Resuscitation Crystalloids

Na
(mEq)

Cl
(mEq)

K
(mEq)

NS
(0.9%)

154

154

LR

130

109

PL

140

98

Ca
(mEq)

Mg
(mEq)

2.7

Lactate

Acetate

Gluconate

28
3

27

23

pH

mOsm

Other

5.0

308

Indicated in
neurosugery
cases

6.5

273

Contraindicated
in liver and
kidney failure

7.4

294

Physiologic pH

Type and Screen

Screen for ABO-Rh type and most common antibodies

ABO incompatibility is a tragic and severe reaction, resulting
in rapid intravenous hemolysis
Ordered during elective cases when the probability of blood
loss and transfusion are high
If blood is needed for emergent transfusion, a crossmatch can
be performed to reconfirm ABO-Rh typing
Reactions against lower-incident antigens may still occur
Emergency trauma cases: Type O Rh-Negative (Universal
Donor) Uncrossmatched Blood transfused until a Type and
Cross clot is tested

Type and Crossmatching

Crossmatching
-Trial transfusion within a test tube between donor RBCs and recipient serum to
detect a potential for serious transfusion reaction
- 3 Phases:
-Reconfirm ABO-Rh typing
- Detect antibodies that are incomplete or do not agglutinate
easily
- Detect antibodies in other blood group systems (ie. Rh, Kell,
Kidd, Duffy)

Antibody screening
- Trial transfusion between the recipients serum and commercially supplied RBCs
with antigens that will react with antibodies commonly implicated in non-ABO
hemolytic transfusion reactions
Donors serum also screened for unexpected antibodies to prevent their
introduction to the recipients serum
Otherwise known as the Coombs test.

Blood Products Transfusion

Packed Red Blood Cells

Fresh Frozen Plasma
Platelets
Cryoprecipitate

Packed Red Blood Cells

Approx. 12 000 000 units of RBC are transfused yearly in the US

Indicated for patients needing red cells for oxygen carrying
capacity rather than for volume replacement (ie. CHF patients)
70% Hct in pRBC compared to 40% Hct in whole blood
Each unit contains 250-350 cc of red cells, increases Hct 3-4% or
increases Hgb 1g/dL
Large amount of transfusions should be warmed to 370C
Dilute pRBCs with either normal saline or plasmalyte when giving
massive transfusions
Avoid Lactated Ringers because calcium can chealate with citrate

Citrate Toxicity

Calcium binding to citrate preservative in

transfused blood Hypocalcemia
Signs of citrate intoxication: hypocalcemia,
hypotension, narrowed pulse pressure,
increased end-diastolic pressure
Cardiovascular depression can occur if
transfusion rate > 1 unit of blood per 5 mins
Risk factors: hypothermia, liver disease, liver
transplantation

Fresh Frozen Plasma

Portion of whole blood

that remains after cellular
elements and platelets are
removed
Each unit contains 250cc
plasma
Contains coagulating
factors and fibrinogen
Increases level of each
clotting factor by 2-3%
Needs to be ABOcompatible but does not
require crossmatching Rh
typing

Fresh Frozen Plasma

Indications:
1) urgent reversal of Warfarin therapy
2) correction of isolated coagulation factor deficiencies
3) correction of microvascular bleeding when INR and
pTT >1.5 x normal
4) correction of microvascular bleeding due to
coagulation factor deficiency in patients transfused with
> one blood volume and when PT and pTT can not be
obtained
5) Antithrombin III deficiency
6) Treatment of immunodeficiencies
7) Treatment of thrombotic thrombocytopenia purpura

Platelets

Indicated for thrombocytopenia platelet count < 50 x 109/L

Pooled from donated blood (ie. 5 donors=5000 plt/microL)
Each 10-12 units of pRBC decrease plt count by 50%, for
replacement therapy, 5-10 units of plt (ie. 5000 10 000
plt/microL) should be given when 10-20 units of pRBC has
been transfused
Transfuse SLOWLY to avoid hypotension

Cryoprecipitate

Collected by thawing FFP at 40C, contains von Willebrand

factor, factor VIII, XIII, fibrinogen, and fibronectin
One unit of cryoprecipitate will increase fibrinogen
concentration by 50mg/dL
Indicatation:

Patients with von Willebrands Dz unresponsive to Desmopressin

Bleeding patients with vWD
Bleeding patients with fibrinogen levels < 80-100mg/dL
Hemophilia A

Administer rapidly through a filter (ie. 200 cc/hr, infusion

should be completed within 6 hrs of thawing)

Coagulation Cascade

Pathophysiology of Coagulopathy in
Massive Transfusions
Coagulopathy results from:
hemodilution
hypothermia
unfractionated blood products
DIC

Hemodilution

Crystalloids
-1/4 stays intravascularly, 3/4
goes into interstium
-Dilute platelet and coagulating
factors

Colloids
-Hespan and Dextran impair
platelet adhesion by decreasing
von Willebrand factor activity
-Impair thrombin and clot
formation

Hypothermia
Hypothermia (<35 degrees):
slows activity of coagulation cascade
reduces synthesis of coagulation
factors
increase fibrinolysis
decrease platelets and affects platelet
function
Hypothermia and acidosis cause
significant bleeding despite adequate
blood, plasma and plt replacement

Blood Components

Red Blood Cells-contribute to thrombosis and hemostasis

-Contain ADP that activates platelets, activate platelet
cyclooxygenase, increase generation of thromboxane A2,
increase thrombin
-Abnormalities of Prothrombin time (PT) and activated
partial thromboplastin time (aPTT) occur after transfusion
of 12 units of pRBC
Coagulation Factors-Blood loss greater than EBVx2
resulted in deficiency of prothrombin, factor V, factor VII,
and platelets
Platelet- Thrombocytopenia occur after transfusion of 20
units of pRBC

Disseminated Intravascular
Coagulation

An acquired syndrome secondary to systemic and excessive

activation of coagulation.
Tissue trauma, brain injury, shock, tissue anoxia,
hypothermia contribute to DIC
Diagnosis: D-dimer>500mcg/L, increased INR,
thrombocytopenia, microvascular bleeding +/- thrombosis
Risk factors: acidosis, hypothermia, hypotension, increase in
injury severity

Transfusion Service Protocol at

Parkland Memorial Hospital, Texas

Cooperative effort between Pathology, Anesthesiology

and Trauma Surgery

Goal: to support rapid transfusion in ER and OR with

regular shipments of blood products released
automatically on a timed basis

Design for massive transfusion protocol is based on

patterns of coagulopathy that may develop during trauma
care

Patient survival to date appox. 50% with the protocol

Transfusion Service Protocol

Shipments

#1

#2

#3

#4

5 units pRBC +
2 units FFP
q30mins

Platelets (5
pooled units)

Cryoprecipitate
(10 pooled unit)

rFVIIa
(sent at pRBC
units 11-15)

Human Recombinant Factor VIIa

Vitamin K-dependent glycoprotein

Indications: treatment of bleeding in
hemophilia A and B, acquired inhibitors
(e.g. anti-VIII), and congenital factor
VII deficiency bleeding
Site of action: extrinsic coagulation
cascade
Promotes activation of factor X to Xa,
and factor II (prothrombin) to IIa
(thrombin) - bypassing the intrinsic
pathway
Promotes clot formation and
hemostasis at the site of injury
Shorten the prothrombin time (PT)
Extent of PT shortening does not
correlate with clinical efficacy of
rFVIIa need for monitoring blood
loss, transfusion requirement, and
hemoglobin

Image from: www.itxm.org/images/coag1.jpg

Human Recombinant Factor VIIa

Efficacious adjuvant therapy in managing hemorrhage due to

trauma
Reduce the need for massive blood transfusions in blunt trauma
No increased risk for thromboembolic event, DIC, allergic rxn
or thrombocytopenia
Reduced risk assoc. with plasma transmission of virus
Less frequent complications associated with microthrombus
generations such as multi-organ failure and ARDS
Frequent dosing needed due to short half-life (2-3hrs)
Recommended dose: 90 mg/kg, continued every 2-3 hours.
Once bleeding and hemoglobin have stabilized, taper to every
6-8 hours, then every 12-24 hours, and then stop

Management of Coagulopathy in
Massive Transfusions

Maintain core body temp > 35oC

Correct Acidosis by re-establishing adequate tissue perfusion
and oxygenation
Check labs (ie. ABGs, lytes, coags, plt, fibrinogen, lactate)
Replete electrolytes (ie. Calcium)
Early administration of FFP and platelets during massive
transfusion with pRBC

Stay ahead of the game to prevent coagulopathy

in the first instance