AUSTRALASIAN SOCIETY OF BLOOD TRANSFUSION INC.

Topics in
Transfusion
Medicine
September 2000
Vol 7 No 2

u Editorial Board
Editor:

Ken Davis

Board Members:

Margaret Buring, Wendy Erber, Jim Faed, John Gibson,

Robyn Minchinton, David Roxby

Editor's Note
This issue is a pot pourri of various matters, hopefully of interest to a range of members.
Cord blood banking and transplantation is now becoming commonplace in various centres worldwide. The reprinted article form the Institute for Transfusion Medicine [ITxM] Pittsburgh discusses
some of the benefits and difficulties of this new treatment modality.
We are continually faced with areas of blood wastage and at ways of looking to reduce this. The
Californian Blood Bank Society e_network Forum article of the use of unused thawed FFP presents
some thoughts on this particular matter.
In many transfusion laboratories the request to process and store preadmission samples is increasing.
The third edition of our own pretransfusion guidelines deals with this matter. For added interest the
ITxM article on this matter is reprinted for members.
Some time back Lara Griffin, ARCBS, Sydney, posted a question on our own e-mail network regarding
red cell selection in PTP and NAIT. This sent a number of us to the text books and the question was
also posted on the AABB web page. The questions that Lara posed and the response from the AABB
site are published for interest and comment.
Lastly a report from John Lown on the recent WAA/HSANZ/ASBT conjoint meeting in Perth.
Members are encouraged to let the Editor know what topics they would like addressed in future
issues.
Ken Davis
[ken.davis@imvs.sa.gov.au]
Extra copies of Topics in Transfusion Medicine are available from the ASBT office for $20 each.
Please spread the word.
All Correspondence
The Australasian Society of Blood Transfusion Inc
145 Macquarie Street, Sydney NSW 2000

September 2000
Vol 7, No 2

CONTENTS
1. Cord Blood Banking and Transplantation
Richard Moldwin, MD PhD, Medical Director, ITxM Cord Blood Services
Transfusion Medicine Update, Institute for Transfusion Medicine,
Pittsburgh, PA
[reprinted with permission]

Page 1

2. Minimising Wastage of Unused Thawed FFP

e-Network Forum, Californian Blood Bank Society
[reprinted with permission]

Page 4

3. Elective Surgery, Preadmission Testing and The Transfusion Service

Ileana Lopez-Plaza, MD, Associate Medical Director, Transfusion Services
Transfusion Medicine Update, Institute for Transfusion Medicine,
Pittsburgh, PA
[reprinted with permission]

Page 8

4. Selection of red cells in PTP and NAIT

ASBT member inquiry and response from AABB website.

Page 10

5. Congress Report WAA/HSANZ/ASBT Perth July 2000

John Lown, ASBT Hon. Secretary

Page 12

September 2000
Vol 7, No 2

1. Cord Blood Banking and Transplantation

Richard Moldwin, MD, Ph.D., Medical Director, ITxM Cord Blood Services

Introduction: Haematopoietic stem cell transplantation can provide a cure for a variety of

malignant and non-malignant disorders (Table 1). In autologous transplants, the patients own
stem cells are collected and stored for later transplantation. In allogeneic transplants, the
transplanted stem cells are derived from a related or unrelated donor. In many cases, an
allogeneic, rather than autologous, transplant is preferred for treating malignant and nonmalignant diseases. Siblings who match the patient for cell surface HLA proteins offer the best
option for allogeneic graft compatibility and a good outcome.

HLA Matching: Unfortunately, matched sibling (allogeneic) donors are available to only

about 30% of those in need of an allogeneic transplant. To help provide matched unrelated
donors for these patients, large registries of volunteers willing to donate marrow (or
peripheral blood stem cells) to unrelated recipients have been established (eg. the National
Marrow Donor Program). However, finding appropriate matches for many patients remains
difficult.

Cord Blood Stem Cell Transplants: One solution to the shortage of matched donors
may be found with umbilical cord blood (CB), which is a rich source of haematopoietic stem
cells. CB has been used successfully in place of bone marrow in children and a few adults
undergoing stem cell transplantation. Since the first CB transplant in 1987, more than 800
such transplants have been done in the US and Europe.

Graft versus Host Disease is Decreased with Cord Blood: Recent data indicate

that CB transplantation is associated with significantly decreased severity of T cell-mediated

graft-versus-host disease (GvHD), when compared with historical data from matched
unrelated bone marrow transplants. Acute GvHD is a syndrome of dermatitis, enteritis, and
hepatitis occurring within 100 days of the transplant. Chronic GvHD, by definition, develops
after 100 days post-transplant. Chronic GvHD is similar in many respects to collagen-vascular
diseases such as scleroderma and lupus. Both acute and chronic forms of GvHD are major
causes of morbidity and mortality for patients undergoing allogeneic stem cell transplantation.
With CB transplants, the decreased incidence of severe GvHD now permits the routine use of
relatively mismatched CB units. The ability to use mismatched CB units therefore allows many
more patients to be transplanted. However, engraftment and survival rates are still improved
with close HLA matches.

Cord Bloods Other Advantages: Although CB T cells are less likely to produce serious

GvHD, early data suggests that they can still be effective in suppressing or eliminating
malignant cells remaining in the transplant patient. The presence of a graft-versus-tumour
effect is being closely studied in CB recipients.
There are several other advantages to CB as well. Since CB units are stored frozen, they can
be released immediately to patients in need of a transplant. In contrast, setting up an
unrelated donor stem cell harvest (bone marrow or peripheral blood stem cells) can take
several months.
CB collection also poses no risk to the mother or baby, whereas both bone marrow harvests
and G-CSF-mobilized peripheral blood stem cell harvests have been associated with occasional
serious morbidity and even mortality.
September 2000
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Cord Bloods Disadvantages: Since the numbers of CB stem cells may be insuffic ient to
engraft a large patient (ie. an adult or large child), the patient may die before engraftment
takes place. Even in small patients, where the stem cell numbers are sufficient, engraftment is
usually significantly delayed (~28 days for neutrophils, ~90 days for platelets) when
compared with peripheral blood stem cells (~7 days for neutrophils, ~9 days for platelets).
A further problem is that a patient who does not engraft cannot easily obtain more stem cells
from the CB donor (who is probably still a small child). In contrast, adult unrelated donors
may donate stem cells more than once for the same transplant patient.

The Growing Use of Cord Blood: The shortage of matching CB units can addressed by

the establishment of CB "banks" throughout the world. There are currently about 25,000 units
of CB stored worldwide in CB banks. These CB banks are a life-saving resource for many
patients, who would otherwise die for lack of a suitable stem cell donor. There is a pressing
need for the expansion of CB donor banks to ensure that all patients needing a stem cell
transplant are offered a CB unit with a suitable HLA match.

Autologous Cord Blood Storage : CB stem cells have not yet been used for autologous

transplants (ie. using a childs stored CB for a transplant in that same child, later in life).
However, commercial CB banks have begun to sprout up throughout the country, advertising
autologous CB storage services. The charges for these services range from about $275 to
about $1500, not including yearly storage fees (usually $50-100 per year). Estimates on the
chances of a child ever using such an autologous CB unit for transplant range from 1/10,000
to about 1/50,000. If the family has many children, the stored CB may be of most benefit to
an HLA-matched sibling who needs a transplant. However, even in this case, the sibling CB
donor should still be available to donate peripheral blood stem cells or marrow. Although the
future uses of stored autologous CB are unknown, autologous CB storage would appear to be
of marginal benefit.

Public Cord Blood Banking: In contrast to autologous CB banking, "donor banks" or

"public banks" have been established throughout the world for the cost-free collection of units
for use in stem cell transplantation. The Institute of Transfusion Medicine (ITxM) has recently
established a public cord blood bank. ITxM Cord Blood Services (ICBS) collects, tests, and
freezes units of umbilical CB. It is a community resource dedicated to providing units of CB for
stem cell transplantation and medical research. CB units collected in the Chicago and
Pittsburgh areas will be released in the US as well as abroad, in conjunction with the NMDP.

Recruitment of Donors: Recruitment to donate CB is done by word of mouth or through

interested obstetricians, nurses and nurse-midwives. The potential donor (mother) is asked to
consent to:
Providing medical, ethnic, and related information
Donating CB to the CB bank for transplantation and/or research
Providing 7 cc of maternal blood for tests, including HIV testing
Providing information about the newborn's medical history

Collection: After delivery of the newborn, the obstetrician, midwife, or nurse collects the

cord blood using two 60 ml syringes containing an anti-coagulant (CPD-A1). CB stem cells
survive for at least 2 days in the collection syringes at room temperature. No blood is drawn
from the infant for testing.
September 2000
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Processing: When the CB arrives at the processing facility, it is separated into red cell,

white cell, and plasma components. The white cell component, which contains the stem cells,
is cryopreserved using DMSO and Dextran as cryoprotectants. The CB is cultured to detect
microbial contamination, and assays of stem cell activity are performed before freezing. In
addition the mothers blood is tested for HIV, Hepatitis B & C, HTLV I & II, Syphilis, and CMV.
Once the CB is safely frozen, it is HLA-typed, and registered for searching through the NMDP.

Future Prospects: Although there are still hurdles to be overcome using cord blood, this

new approach offers a new chance at life for many patients. In the future, new developments
in stem cell expansion, amelioration of GvHD, and immunotherapy should further refine cord
blood transplantation into a cure for many more patients.
TABLE 1

Some Diseases Treated with Cord Blood

Transplantation

Acquired Haematological Disorders: ALL< AML< CML<

Myelodysplastic Syndromes, Non Hodgkin Lymphoma, Aplastic
Anaemia
Solid Tumours: Neuroblastoma, Breast Cancer
Histiocytic Disorders: Langerhans Cell Histiocytosis, Familial
Erythrophagocytic Lymphohistiocytosis
Congenital Haematological Disorders: Blackfan-Diamond
Anaemia, Congenital Amegakaryocytic Thrombocytopenia,
Congenital Pure Red Cell Aplasia, Kostmanns Syndrome, Fanconi
Anaemia
Congenital Immunodeficiencies: Leucocyte Adhesion Deficiency,
Bare Lymphocyte Syndrome, Severe Combined Immunodeficiency,
X-linked Lymphoproliferative Disease, Wiscott-Aldrich
Misc. Congenital Disorders: Gunthers Disease, Osteopetrosis,
Dyskeratosis Congenita, Hurlers, Hunters, Inherited Neuronal Lipoid
Fuscinosis, Lesch-Nyhan, Adreno leukodystrophy

September 2000
Vol 7, No 2

2. Minimising Wastage of Unused Thawed FFP

e-Network Forum, Californian Blood Bank Society.

A member of the CBBS e-network wanted input regarding the high wastage of unused
thawed FFP on their transfusion service. This occurs under two situations:
1. The FFP has been dispensed by the laboratory, but is returned (typically less
than several hours after thaw). In this case, if the plasma has been out of
refrigeration for more than 30 minutes and then returned to the lab, it is
considered to be an automatic discard.
2. In other cases the FFP is ordered but is not picked up. The transfusion service
holds the thawed FFP in their refrigerator for up to 24 hours before discarding it.
The inquiring member wanted to know if other hospitals were relabelling their 'thawed-butalways-refrigerated' FFP as "thawed plasma" at 24 hours, and then storing it for up to 5
days post-thaw and dispensing this plasma to fill FFP orders? If so, are there clinical
indications for which this component is prohibited beyond sole source factor VIII source?
There are studies in the literature showing reasonable preservation of factors V and VIII,
even up to 28 days post thaw (Transfusion 1993; 33:735-8). Have others done their own
in-house studies?
What about the FFP which has been dispensed by the laboratory and then returned? There
are studies showing that 24 hour room temperature storage of whole blood (Transfusion
1999; 39:488-91) or thawed FFP (Transfusion 1980; 20:546-8) have quite good stability of
factors V and VIII over this interval. If FFP is returned to the laboratory and put back into
refrigeration, is it permissible to give this plasma a 24 hour outdate? (See final response
below.)
What follows are the replies of several e-network members.
One member replied that their approach is to try to limit the number of units thawed
at any one time. This member's blood bank advises the requesting physician that units
will be thawed quickly when actually needed. This approach seems to help avoid thawing
plasma that is not actually needed. When an order is received, this blood bank inquires of
the ordering physician how many units they want to give immediately, and thaws only
that number of units - often only one unit at a time. For more units the blood bank requires
about twenty minutes advance notice and units will be thawed as they are needed.
Wasted units and follow-up with the ordering physician are documented through
the Transfusion Committee.
[WebMaster NOTE: While this approach may work in some settings, limiting access to FFP
to one unit at a time, with a 20-minute delay per unit, may not be practical in other
settings, such as a trauma center.]
A second member replied that his institution monitors ordering by physician. All units of
FFP that are ordered, thawed, and not used are included in their blood utilisation
review. This physician-specific data is used for purposes of recredentialing. The member
reports that they have only rare units that are thawed and not used.

September 2000
Vol 7, No 2

A third member replied that in his area, the wastage of FFP often happens on TTP
patients whose exchange gets cancelled or postponed.
This member's blood bank relabels the product as "Liquid Plasma", storing it a 4oC
until the next scheduled plasma exchange, as described in the AABB Technical Manual. The
new expiration date is 5 days from the time the product was thawed.
A fourth member's blood bank routinely uses FFP which has been thawed but not issued.
After 24 hours the FFP is relabelled as thawed plasma and used up to 5 days. This has
been very convenient for trauma patients. Using this inventory management approach the
blood bank saved $3,300 in 1999.
A fifth member commented that she was concerned about another issue, besides the
viability of the product . Her concern was why are all these products being requested
and not used? Her blood bank has had success with educating the nursing staff and,
with their Blood Bank director, addressing the issue through Medical committees.
The member works at a transplant center, where about a year ago their monthly statistics
showed that a significant number of units of FFP were wasted each month. They identified
that the transplant MDs were requesting up to 10 units of FFP to be thawed for
each case and not using the product.
This was discussed in their Transfusion Committee and then the issue was taken up with
the specific Medical committee. The result was that the pre-op ordering routine was
changed to reduce the number of FFP units prepared for surgery for these patients.
A sixth member commented that when she was in the hospital environment, her blood
bank set up an ordering system where they were able to distinguish between a
"hold this in case I need it" order (in which case the blood bank would not thaw)
and a "transfuse this on this date" order (in which case the blood bank would
thaw). In this member's opinion, relabelling and trying to "recover" the plasma wasn't
going to prevent the waste. She felt education might help.
A seventh member stated it was their policy for FFP that has been thawed and
refrigerated to issue it as FFP, provided it is used within 24 hours of thawing. After
24 hours the unit is discarded. As for products issued and kept at room temperature for
an extended period of time, it is their policy to return them to the Blood Bank for discard.
An eighth member had this to offer. Blood components leaving the blood bank and
laboratory for an extended period of time create problems with regard to how they are
stored and how storage conditions are documented. Some hospitals have O.R. refrigerators
dedicated to holding blood components (RBC's and FFP) until they are needed. If the
components are not used they can be returned at any reasonable time (within expiration
dates or times), provided that proper re-identification procedures are followed on the
components after their return to the blood bank. The medical center at which I worked
used this system for around the last five years in their open heart surgery rooms. The
refrigeration also inhibits bacterial contamination of FFP and RBC's. The problems arise
when you have more than one patient with more than one type of unit/component and so
on. The program at this medical center has low numbers of such cases, so there is less risk
of errors resulting from this kind of practice. This member believes there is a far greater
wastage of FFP and blood in the E.R., other operating rooms, and ICU's where there can be
many units transfused and/or "wasted". In these areas it can be diffic ult to apply this kind
of policy/procedure, due to cost and respective practicality. As for FFP, there is an
alternative with SD-Plasma (Plas+SD).

September 2000
Vol 7, No 2

alternative with SD-Plasma (Plas+SD).

This component has been sterile -filtered and post thaw is good for 24 hours at room
temperature. Therefore returns after 30 minutes should not be a problem.
This member is interested in finding out how much standard FFP is wasted due to this 30minute return limit at major surgical and trauma centers. It could be an added reason to
use SD-Plasma, even though unit costs are higher.
Finally, in response to the question about post thaw stability of 'labile' coagulation
factors a member stated there is published data that factor V has reasonable levels at 5
days post thaw, but levels of factor VIII drop lower. The FDA has been willing to accept a
notation that, based on cited studies in the literature a label of thawed plasma can be
used, and the plasma can used for up to 5 days post thaw, provided it has been
refrigerated. The caveat is that the "thawed plasma" will not be used for factor VIII
replacement. Since most hospitals use factor VIII concentrates for such replacement, this
limitation is not necessarily a problem.
Additional comments or suggestions are encouraged by contacting me.
Ira A. Shulman, MD
CBBS e-network Web Master
Web Master Note:
The following information was provided to me by Kay Gregory of the AABB who states that
the new Circular of Information (if approved by the FDA) will address thawed plasma - in
a fashion very similar to that in the current edition. The circular addresses the approved
uses. Here is what it says:
Plasma Components Containing Reduced Amounts of Labile Coagulation Factors
Description
Other Plasma components may be made from whole blood collected in all approved
anticoagulants or by apheresis. These components contain stable coagulation factors such
as factor IX and fibrinogen in concentrations similar to that of FFP, but reduced amounts of
factors V and VIII. The volume is indicated
on the label.
Actions
These components serve as a source of defective or deficient plasma proteins except for
Factor V and factor VIII.
Indications
As for FFP, except that these components should not be used to treat coagulation factor
deficiencies of factor V and factor VIII:C
Contraindications
Do not use Plasma, Thawed Plasma, or Liquid Plasma for replacement of coagulation
factors V and VIII. Otherwise, the contraindications are the same as for FFP.
Dosage & Administration
Same as for FFP.
September 2000
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Side Effects and Hazards

Same as for FFP.
Components Available
1. Thawed Plasma is derived from FFP prepared in a closed system, thawed at 30-37 C,
and maintained at 1-6 C for 1-5 days.
2. Plasma Frozen Within 24 Hours After Phlebotomy must be separated and placed
at -18 C or below within 24 hours from whole blood collection.
3. Plasma; Liquid Plasma is separated no later than 5 days after the expiration date of
the Whole Blood. Plasma may be stored at minus 18 C or below. Liquid Plasma is stored at
refrigerator temperature (1-6 C).
Entered: April 2, 2000
Revised: April 5, 2000

September 2000
Vol 7, No 2

3. Elective surgery, preadmission testing, and the transfusion service

Ileana Lopez-Plaza, M.D., Associate Medical Director, Transfusion Services

Introduction

Increasingly, admissions for elective surgical procedures are occurring the same day of
surgery. Most preoperative laboratory testing is completed days in advance of the scheduled
procedure. This often does not include blood bank testing, creating a logistic challenge for
the transfusion service when patients are admitted when patients are admitted.
Typically, patients must present to the preop holding areas a few hours before a scheduled
procedure. For surgical cases requiring the use of blood, a sample is drawn at this time for
compatibility testing. Often this provides less than two hours of turn-around-time to
complete testing before a scheduled surgery. Any delay in blood availability can impact the
patient and operating room schedule significantly.

Preadmission blood bank testing

Samples for compatibility testing can be collected up to 14 days prior to a scheduled

procedure. Typing, screening, and crossmatching must be performed by the blood bank
servicing the facility where the procedure is to be done. Blood needed for surgery can be
crossmatched the night before surgery, preventing delays in blood availability the day of the
procedure. Further, it allows time to evaluate a positive antibody screen and obtain
compatible blood for these patients. Samples drawn at preadmission are tracked to the
patient the day of the surgery by comparing a unique numeric identifier present on both the
band that the patient was provided with at the time the sample was drawn, as well as on the
blood sample itself. This identification band provides the only link between the patient and
the sample.
In order to perform preadmission testing, patients need to meet the following criteria: a) the
patient has not been transfused or pregnant in the past three months; b) the band provided
to the patient at time of the sample was drawn is present on the patient, the day of surgery.
Patients, who do not meet these criteria, must have their sample drawn within three days
before surgery. Samples drawn the day of surgery, must be collected a minimum of two
hours beforehand in order to complete testing once the sample has reached the blood bank.
Patients with positive antibody screens will require additional time for antibody identification
and blood availability. Depending on antibody specificity, it may take hours or more for blood
availability. Patients drawn in advance, who do not have the band on them the day of the
surgery will need to be redrawn, and all testing repeated prior to the release of
crossmatched blood.

Supplementary preoperative blood bank features

Preoperative services that the blood bank provides include preoperative autologous blood
donations and the Maximum Surgical Blood Ordering Schedule (MSBOS).
MSBOS
MSBOS is based on data collected from surgical records of blood usage at an institution. The
MSBOS provides recommendations on the maximum number of units to order for common
elective procedures. Options for testing include no blood required, type and screen required,
or type and crossmatches, stating the number of units to be crossmatched. It is
recommended that surgeons, who routinely require less than one unit of blood, should only
order a type and screen.
September 2000
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Once the MSBOS is established, the transfusion service will follow these guidelines to meet
blood requirements for each patient undergoing that particular procedure.
MSBOS facilitates the availability of blood for surgery by minimizing the amount of blood tied
up in the crossmatch inventory. Also, it prevents patients from going to the OR without
sufficient blood ordered.

Preoperative autologous blood collections

Autologous blood collection should be attempted for every medically eligible patient
undergoing an elective surgical procedure who will require transfusion.
Contraindications for autologous donations generally include cardiovascular disease with
compromised hemodynamic reserves or risk of bacterial contamination of the collected
blood.
Unnecessary collection of autologous blood is not without risks to the donor. The decrease in
haemoglobin levels put the patient at risk for transfusion. Units are typically collected on a
weekly basis and no less than 72 hours prior to surgery.
Blood ABO and Rh typing are the only required tests for an autologous unit collected and
transfused in the same facility. However, autologous units that are collected by a blood
center need to be fully tested (including viral markers) in order to be distributed to the
hospital facilities. Autologous blood donation is best ordered as packed red cells versus
whole blood, in order to extend the shelf life of that unit up to six weeks after collection.

Summary

Most transfusion services provide options that facilitate blood availability for surgery.
Physicians (surgeons, primary care), medical institutions, and health insurance companies
should maximise the use of these benefits provided by transfusion services.
Copyright 1999, Institute For Transfusion Medicine

September 2000
Vol 7, No 2

4. Selection of red cells in PTP and NAIT

Questions

Lara Griffin, ARCBS, Sydney.

My thoughts and some references

By Jeffrey L Winters MD. [AABB site]

The questions you ask are interesting. Here is my opinion with some references to
support them. I must admit that this comes mostly from reviewing the literature. I have
been involved in the care of only one patient with PTP and about ten patients with NAIT.
The majority of the latter have been due to anti-HPA-1a.

Question 1 - What are the indications for the transfusion of HPA-1a

negative red cells?
One indication would be the presence of anti-HPA-1a as in cases of previous PTP or NAIT
(see question 3).

Question 2 - Should HPA-1a negative red cells be issued to HPA-1a

negative patients?
Approximately 2 - 3% of Caucasian donors are negative for HPA-1a. Of these, only those
possessing DRw52 are at risk of becoming sensitised.
(Blanchette et al: Alloimmunisation to the PLA1 platelet antigen; results of a prospective
study. Br J Haematol. 1990; 74; 209-2 15,
Valentin et al; HLA-DRw52a is involved in alloimmunisation against PLA1 antigen. Hum
Immunol 1990;27; 73-79,
de Waal et al: Alloimmunisation against platelet specific Zwa antigen, resulting in
neonatal alloimmune thrombocytopenia or post-transfusion purpura, is associated with
the supertypic DRw52 antigen including DR3 and DRw6. Hum Immunol 1986; 17:45-57).
Even those possessing the appropriate HLA antigens may not become sensitised to HPA1a.
(Panzer et al: Maternal alloimmunisation against foetal platelet antigens; a prospective
study. Br J Haematol. 1995; 90; 655-660).
Since PTP and NAIT can cause mortality or significant morbidity, one could argue for
giving antigen negative blood products to prevent alloimmunisation. I have not seen this
discussed in the literature that I have reviewed. Should all patients be typed for HPA-1a
to identity those that are negative? Should one consider typing for DRw52 and giving
antigen negative blood to those who are negative for HPA-1a and positive for DRw52? A
strategy similar to this has been suggested with regard to screening pregnant women for
anti-HPA-1a antibodies.
(Doughty et al; Antenatal screening for foetal alloimmune thrombocytopenia; the results
of a pilot study. Br J Haematol. 1995; 90; 321-325,
September 2000
Vol 7, No 2

10

Durand-Zaleski et al; Screening primiparous women and newborns for foetal/neonatal

alloimmune thrombocytopenia; a prospective comparison of effectiveness and costs.
Immune Thrombocytopenia Working Group. Am J Perinatol. 1996; 13:423-431).
One could type a known HPA-1a negative patient for DRw52 and proceed from there with
regard to giving antigen negative products.

Question 3 - Should HPA-1a negative red cells be issued to an HPA-1a

negative individual with anti-HPA-1a?
PTP due to anti-HPA-1a has been reported to recur upon rechallenge with antigen
positive blood products in some
(Taaning et al; Post-transfusion purpura; a survey of 12 Danish cases with special
reference to immunoglobulin G subclasses of the platelet antibodies. Transfus Med 1994;
4; 1-8,
Budd et al; Relapsing post-transfusion purpura. A preventable disease. Am J Med 1985;
78; 361-362)
but not all cases.
(Lau et al; Post-transfusion purpura; an enigma of alloimmunisation. Am J Hematol 1980;
9; 33 1-336).
In addition, a single case has been reported where PTP occurred in a woman with a
previous history of an infant affected by NAIT due to anti-HPA-1a.
(Cobos et al; Post-transfusion purpura and isoimmune neonatal thrombocytopenia in the
same family. Am J Hematol. 1989; 32; 235-236).
These would lead me to believe that HPA-1a negative products should be given to
sensitised patients. Now, should the red cells be from HPA-1a negative donors? Most
places in the US do not type their donors for HPA antigens and so finding antigen
negative donors are difficult. PTP occurs not only with products containing platelets but
any product containing plasma from the HPA-1a positive donor. It is thought that soluble
HPA-1a in the plasma is responsible for this (Kickler et al: Studies on the pathophysiology
of post-transfusion purpura. Blood 1986; 68:347-350).
With this in mind, the use of washed red cell products has been reported in the
treatment of a patient with PTP.
(Gabriel et al: Post-transfusion purpura due to HPA-la immunisation in a male patient:
Response to subsequent multiple HLA-la-incompatible red-cell transfusions. Transfus
Med 1995; 5: 131-134).
This may represent another option for sensitised patients that would be a lot easier to do
than find HPA-1a negative red blood cells. However, the use of washed red cells has
been reported to precipitate PTP as well so if antigen negative red cells were available,
they would probably be preferable to washed products.
(Godeau et al: Le purpura post-transfusionel une cause meconnue de thrombopenie aigu
immunologique. Presse Med 1990; 19: 1974-1977).
September 2000
Vol 7, No 2

11

5. WAA/HSANZ/ASBT 2000 Congress Report

John Lown, ASBT Hon Secretary

The Congress in Perth portrayed an additional dimension to the usual annual scientific
meetings of the HSANZ and ASBT. The involvement of the WAA resulted in more than the
usual number of international identities participating than would normally be the case at
our national meetings, with consequent benefits to the programme. With up to 7
concurrent sessions running at times, there was inevitable difficulty deciding which
session to attend. Some topics covered included:

Viral Inactivation of Blood Products

A significant focus at the meeting was the evolving technology for viral inactivation of
blood products. For plasma derived products, two steps are generally required in the
processing to ensure removal of both enveloped and non enveloped viruses.
Chromatographic purification of plasma components separates viruses from the target
product, solvent detergent processing inactivates enveloped viruses, and various wet
and dry heat processes are used in addition for further inactivation, in particular of non
enveloped viruses such as HAV and Parvovirus.
Solvent-Detergent prepared plasma (SD plasma) is now licensed for use in 9 European
countries. FFP has been discontinued in favour of virally inactivated product in Belgium,
Norway, Germany, France and Holland. The benefits of using SD plasma vs FFP include ;
greater consistency in coagulation factor content, reduced contamination with leucocytes
and debris, reduced incidence of TRALI and production of a standardised volume per unit.
Other agents being evaluated for plasma inactivation include psoralens and methylene
blue. These agents require light activation.
Viral inactivation of platelet concentrates has been examined using photosensitised
psoralens, inactines, Thionine and Riboflavin. With the exception of Riboflavin, there have
been concerns about the possible toxic byproducts of light interaction with the chemical
agent, the possible adverse effects on the quality of the product and the potential for
long term effects from repeated exposure to these agents.
Riboflavin ( vitamin B2) offers greater promise. The photoproducts have so far been
found to be effective in inactivating a range of infectious agents. The adverse impact on
product quality has been found to be no greater than that experienced with other agents
and there appears to be minimal toxic effects.
Several agents are being investigated for viral inactivation of red cell products. S-303
( FRALES a hydrolysable compound) and PEN110 (an Inactine) are in phase 1 clinical
trials. These agents inactivate virus by binding to nucleic acid. However they are
mutagenic and need to be removed from the product before transfusion.
Other options being explored are phthalocyanines which are activated by red light and
phenothiazines, in particular DMMB ( methylene blue). These agents inactivate only
enveloped viruses.

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Blood Group Antigens Structure & Function

Geoff Daniels from the Bristol Institute of Transfusion Sciences provided a lucid update on
the structure & function of red cell antigens. The emphasis was on the functions of some
of the antigens, as little is known about the precise functions of many blood group
antigens.
Some functions have been defined. There are membrane transporter glycoproteins eg
Diego ( anion exchange, CO2 transport), Kidd ( urea transport), Colton ( water transport).
Several antigens have been identified with receptor and adhesion molecules. The Duffy
antigen is a receptor (DARC) for several chemokines including ILA, MGSA, MLP-1 and
RANTES. The Ig superfamily of adhesion molecules and receptors includes Lutheran
(binds laminin), LW ( ICAM4, integrins), Oka ( located on CD147) and In.
Cromer and Knops antigens have been associated with the regulation of complement
activation. The Knops antigen represents the CR1 receptor.
The Kell and Yt antigens are associated with enzyme activity ( endopeptidases and
acetylcholinesterase respectively), but the functions are unknown.
A current project being conducted by Geoff Daniels involves the culture of erythroid cell
lines from stem cells and examining the development of blood group antigens. The
evolution of expression of different antigens may assist in elucidating their functions.
In culture it has been found that the first structure to appear is glycophorin C followed by
Kell and Rh associated glycoprotein (RhAG) by day 4. GPA appears on day 6, band 3 on
day 8 and Rh protein (D,C,c,E,e) and LW on day 10. These are followed by glycophorin
B, Fy and Lu. The presence of serum in the culture medium enhanced the development
of erythroid markers.
The early development of the K antigen gives rise to the hypothesis that the occurrence
of foetal anaemia in the absence of hyperbilirubinaemia associated with anti-K induced
HDN, may be due to defective erythropoeisis caused by anti K mediated destruction of K+
erythroid progenitor cells.

Bioactive Substances and Post Operative Complications

Hans Nielsen presented interesting results on some of his work in examining the
association between levels of various bioactive substances in blood products and clinical
outcomes post operatively. While the mechanisms governing the immunomodulatory
effects of blood transfusion are still being elucidated, Nielsen has focussed on the role
substances released from platelets and white cells have in the inflammatory response and
cancer cell growth. These substances include free oxygen radicals such as
myeloperoxidase, and angiogenesis stimulators PAI-1 and VEGF. VEGF ( vascular
endothelial growth factor) has been found to be 10 x higher in transfused cancer patients
and in patients with solid tumours. Cellular blood products have been found to
accumulate increasing levels of VEGF and PAI-1 on storage. Soluble VEGF levels are
considered to be a prognostic factor in the prognosis of colorectal cancer.
There is also some evidence to suggest that transfusion may influence de novo cancer
occurrence eg NHL.
The data presented suggest that pre storage leucoreduction may improve the outcomes
of transfusion therapy in certain cohorts of patients by reducing the capacity for
acccumulation of biological response modifiers. It also suggests that the extent of
adverse outcomes from transfusion is directly related to the age of the product.
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Haemovigilance
The ARCBS Haemovigilance working party presented an update of progress in the
development of a national haemovigilance system. This was preceded by an excelle nt
overview by Lorna Williamson of the Serious Hazards of Transfusion programme
operating in the UK. This programme seeks to identify major transfusion related adverse
events. These include:
Incorrect blood component transfused
Immediate clinical transfusion reactions
Delayed transfusion reactions
TRALI
PTP
TAGVHD
Post transfusion infections
Over a three year period to 1999, 618 cases have been reported to the SHOT programme
of which 54% involved the transfusion of wrong blood/patie nt. 28% were clinical
reactions.
There were 28 transfusion associated deaths; 10 from TAGVHD, 4 ABO incompatibility, 4
TRALI and 10 due to infectious agents.
The major source of error resulting in transfusion of the wrong blood/patient was the
removal of blood from the blood bank. Other causes were sample collection & labelling,
bedside checks, laboratory errors and prescribing errors.
An overview of the pharmacovigilance system currently in place at CSL Ltd was provided
by Margaret Curran. This was a very useful contribution as one of the aims of the
Australian Working Party is to link the haemovigilance programme with the
pharmacovigilance system at CSL.
An Australian pilot study involving two hospitals commenced in January 2000. The
Working Party are now inviting participation from other institutions.

History of Therapeutic Apheresis

The Cohn de Lavaal lecture is the World Aheresis Association equivalent of the Ruth
Sanger Award. This talk was delivered by Alvaro Pineda from the Mayo Clinic and
provided an overview of the history of therapeutic apheresis.
Early experimentation commenced in 1971 for cases of Raynauds disease and
Scleroderma. These efforts were ineffective. In 1972 the first report appeared of
apheresis therapy for Glomerular Basement Membrane Disease. This followed in 1973
with its use for haemophiliacs with factor VIII inhibitors. Subsequently the procedure was
applied successfully to the treatment of Chronic Inflammatory Demyelineating
Polyneuropathy, Guillan Barr syndrome and Thrombotic Thrombocytopenic Purpura.
The first affinity column was incorporated into the lines at the Mayo Clinic in 1980. These
columns were used to bind IgG to increase the therapeutic effectiveness of apheresis.
Currently, in line filtration for other applic ations is being applied. A dextran sulphate
column is used to remove low density lipoproteins and hollow fibre filters packed with
hepatocytes are being investigated for the detoxification of patients requiring liver
transplants.

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