© 2001 Lippincott Williams & Wilkins, Inc.

Volume 8(6) November 2001 pp 387-391

Transfusion triggers for blood components

[Transfusion medicine]

Clark, Pamela MD; Mintz, Paul D. MD

Output...
Blood Bank, Clinical Laboratories, and Department of Pathology,
University of Virginia Health System, Charlottesville, Virginia, USA.
Correspondence to Pamela Clark, MD, Blood Bank and Transfusion
Service, Box 800286, Medical Center, Charlottesville, VA 22908,
USA; e-mail: pc4b@virginia.edu

66 K

Links...

History...

Outline
 Abstract
 Red blood cells during the perioperative period
 Transfusion triggers in cardiac disease
 Transfusion triggers in critical illness
 Red cell transfusion in sickle cell disease
 Red cell transfusion using autologous blood
 Platelet transfusion triggers
 Transfusion triggers for fresh frozen plasma
 Conclusion
  References and recommended reading
 Section Description

Abstract
Whereas there are general guidelines for acceptable transfusion therapy, optimal transfusion
therapy has not been determined for most clinical settings. Recent research has focused on
controlled studies of red cell transfusion in specific clinical settings. Better determinations of
oxygen delivery and consumption are needed to guide clinicians in determining whether
transfusion is justified for patients during the perioperative period, those with coronary artery
disease, and those in intensive care units. For sickle cell disease, the role of transfusion for
acute complications can be life saving; however, the role of chronic transfusion regimens
awaits further research into efficacy. Finally, whereas criteria for the prophylactic transfusion
of platelets in hematologic diseases are well described, relatively little information is available
on the value of platelet transfusion where the absolute count is less than 100,000 but greater
than 50,000. The value of fresh frozen plasma components, both standard and sterilized, also
requires elucidation.

Current standards of acceptable transfusion practice discourage the reflexive transfusion of

blood components at specified transfusion triggers. This being said, there are general
guidelines for acceptable transfusion practice. The report of the NIH consensus conference,
published in 1988, indicated that transfusion of packed red blood cells could be justified in
most situations when the hemoglobin level declined to 7.0 g/dL [1], although more recent
guidelines have set this absolute trigger at 6.0 g/dL [2,3]. Transfusion of packed red blood cells
is almost never indicated when the hemoglobin level exceeds 10.0 g/dL, and it has been
universally condemned as unacceptable routine practice [1,2,3]. Between hemoglobin levels of
6 and 10 g/dL, however, the decision to transfuse rests on a careful, individualized
determination of the patient’s overall clinical status, taking into account any signs and
symptoms of oxygen deprivation and the potential risks and benefits of transfusion.

Similarly, platelet transfusions in a nonbleeding patient are not required until the platelet
count reaches 10,000/µL so long as the patient has no other risk factors for bleeding such as
fever, sepsis, or disseminated intravascular coagulation [2,4]. A platelet count of 50,000/µL is
generally considered acceptable for most surgical procedures [2,4], but there is little guidance
for those patients whose platelet counts are greater than 50,000 but whose clinical condition
may put them at risk for bleeding.

Guidelines for the transfusion of fresh frozen plasma are even less clear. Most transfusion
medicine specialists find the following criteria acceptable: (1) for an international normalized
ratio (INR) greater than 1.5 with anticipated invasive procedure or surgery, (2) for massive
hemorrhage (greater than one blood volume) with an INR greater than 1.5, (3) for treatment of
thrombotic thrombocytopenic purpura, (4) for inherited coagulopathies where a specific factor
concentrate is not available, and (5) for emergent reversal of anticoagulant therapy [2,4].
Although these general guidelines are useful and have prevented unnecessary transfusions,
they provide little guidance in particular clinical settings where it would be useful to know
whether a transfusion is likely to provide substantial benefit to a patient. Research on the
efficacy of transfusion in more specific clinical settings is currently ongoing. Whereas most of
this research has focused on red blood cell components, some investigations of platelet and
plasma transfusions have also been conducted recently.

Red blood cells during the perioperative period

Despite good clinical data demonstrating that hemoglobin levels as low as 6.0 or 7.0 g/dL are
well tolerated in patients without underlying cardiac or pulmonary disease, several recent
studies document that inappropriate perioperative transfusion practice continues [5–9]. At one
hospital, the main determinant of transfusion had been an estimated blood loss of greater than
500 mL. A simple guideline requiring a hemoglobin measurement before transfusion reduced
the overall number of transfusions by 43%[5]. No absolute level of hemoglobin was specified
as a trigger. Even so, this simple maneuver resulted in a marked improvement in transfusion
practice. Similarly, a nationwide multicenter study of transfusion practice in Finland
determined that inappropriate transfusion practices continued despite published guidelines [6].
Transfusions at hemoglobin levels as high as 10.7 g/dL occurred routinely, and many patients
were transfused despite loss of less than 20% of blood volume. The study concluded that
profound changes in transfusion practice were needed.

To that end, recent reviews of transfusion in the perioperative period have focused on
measurable physiologic changes in oxygen delivery and consumption that could be used to
guide transfusion practice [10,11•]. Several parameters that have been identified are oxygen
delivery, oxygen extraction, oxygen consumption, and mixed venous O 2 partial pressure.
Adequate oxygen delivery to the myocardium depends on blood flow and oxygen extraction.
Normally the heart extracts close to the maximum (approximately 50%) of the oxygen
delivered, and increasing oxygen delivery to the heart depends primarily on increasing blood
flow. Oxygen extraction greater than 50% strongly suggests that oxygen delivery is maximal
and that a transfusion is needed to prevent myocardial ischemia. Decreasing oxygen
consumption also suggests deterioration in oxygen delivery, and one review suggests that a
decrease in consumption of greater than 10% justifies transfusion [11•]. Mixed venous O 2 has
also been used as a transfusion trigger although it has been noted that this measurement may
underestimate tissue hypoxia [11•].

Transfusion triggers in cardiac disease

Anemic patients with coronary artery disease should be considered at high risk for myocardial
ischemia because they cannot increase oxygen extraction or blood flow to the heart, and there
has been some concern that anemia is particularly dangerous in this category of patients [12–
14]. Other studies have not demonstrated this phenomenon, at least in the critical care setting
[15••]. Once the lesions of coronary artery disease have been surgically corrected, however,
lower hemoglobin levels are probably preferable. In one study, length of stay, duration of
mechanical ventilation, and time in ICU were not significantly different in patients who
received transfusions for hemoglobin levels less than 8.0 g/dL as opposed to those in a control
group who were transfused per physician order [16]. Further, at least one study has found that
post-cardiopulmonary bypass patients having higher postoperative hematocrit levels are more
likely to sustain postoperative myocardial infarction [17].
Transfusion triggers in critical illness
Patients in intensive care units generally suffer from anemia [18]. Arguably, anemia in these
patients is harmful because increased oxygen delivery is needed to offset the metabolic
demands of critical illness. On the other hand, it is not clear that increasing hemoglobin
actually results in increased oxygen delivery to tissues [19]. Recent studies have attempted to
define transfusion triggers that can guide therapy for these patients [15••,20,21]. The largest
study randomized a total of 838 patients to received transfusions according to liberal and
conservative criteria. Enrolled patients were normovolemic with hemoglobin levels of 9 g/dL
or less at the time of randomization. Patients in the conservative transfusion arm were
transfused only for hemoglobin levels of less than 7 g/dL, and hemoglobin levels were
maintained between 7 and 9 g/dL. Patients in the liberal arm of the study were transfused for
hemoglobin levels of less than 10 g/dL, and their hemoglobin levels were maintained between
10 and 12 g/dL. The findings are as follows: first, there were significantly fewer transfusions
in the arm that restricted transfusions. Overall there was no increase in mortality in the
restrictive arm despite the lower hemoglobin levels sustained by these patients. Of even
greater interest, however, was that the absolute number of deaths was lower in the restrictive
arm for all patient categories and was significantly lower in some of them. The 30-day
mortality was significantly lower in patients who were less than 55 years of age or who had
Acute Physiology and Chronic Health Evaluation (APACHE) II scores of less than 20,
although overall 30-day mortality was not significantly different. Hospital mortality was also
significantly lower. There was no observed difference in mortality in patients with significant
cardiac disease. The authors concluded that a restrictive transfusion protocol with a
transfusion trigger of 7.0 g/dL decreased transfusion rates significantly and possibly improved
survival rates [15••,21].

Red cell transfusion in sickle cell disease

Two important issues must be addressed in transfusion therapy for sickle cell disease: the
actual transfusion trigger and the proper red cell component to transfuse. The lower threshold
for transfusion in sickle cell disease is difficult to determine. It is known, however, that
patients with this illness should not be transfused to hemoglobin values greater than 11 g/dL
(hematocrit no higher than 35) because of the risks of hyperviscosity. Specialized products are
indicated for the sickle cell patient. Guidelines suggest that packed red blood cells be
leukocyte reduced, hemoglobin S–negative, and at least partially phenotype specific.
Leukocyte reduction prevents most febrile, nonhemolytic transfusion reactions, which in turn
prevents unnecessary transfusion reaction work-ups that can delay needed transfusion therapy.
Ensuring that transfused units are negative for sickle hemoglobin ensures that the patient
receives maximum benefit from transfusion, because the goal of most transfusions is to
reduce the level of hemoglobin S. Further, blood containing hemoglobin S does not filter well
through leukocyte reduction filters. Finally, many blood transfusion programs phenotype red
cell units to make sure that the units are patient identical for the Ee and Kk antigens. Some
programs also include Cc. This is done because chronically transfused sickle cell patients
have high rates of alloimmunization—as many as one third of patients in some studies.
Phenotypically matched blood decreases rates of alloimmunization and is therefore
considered efficacious in this patient group [22].

Patients with sickle cell disease can be transfused in the short term to treat complications of
their disease or on a long-term basis to prevent severe complications of sickle cell disease.
Transfusion is appropriate to improve oxygen delivery in such settings as splenic
sequestration, aplastic crisis and hyperhemolysis, acute chest syndrome, stroke, severe
infection, and organ failure. Its value in treating pain crisis and priapism are still the subject of
debate. Transfusion is used to improve oxygen delivery and tissue oxygenation. However,
transfusion must be used judiciously, with careful attention to volume and viscosity so that
untoward complications do not ensue. In some cases, exchange transfusion may permit the
transfusion of a greater volume of red cells without dangerously increasing intravascular
volume [23].

Long-term transfusion regimens are usually reserved for those patients who have had severe
complications from their sickle cell disease, and transfusion is designed to prevent a
recurrence. Most commonly, long-term transfusion regimens are used to prevent recurrence of
central nervous system events. Maintaining the hemoglobin S at less than 30% has been found
to decrease the rate of stroke recurrence by 90%. More recent studies suggest that hemoglobin
S levels as high as 50% can be tolerated in patients who have been neurologically stable for
more than 3 years. Other patients who may benefit from long-term transfusion therapy are
those with recurrent acute chest syndrome, severe chronic anemia caused by concomitant
renal failure, chronic pain, and heart failure. Other uses of long-term transfusion therapy must
be considered controversial at this time [23].

Red cell transfusion using autologous blood

The transfusion trigger for autologous units has been a matter of debate. On the one hand,
autologous units do not carry with them the risk of disease transmission or immunologic
incompatibility, making a higher transfusion threshold possible. On the other hand, these units
are not risk free and are still subject to the problems of bacterial contamination, cytokine
accumulation, and clerical error. Because of these risks, many have argued that the transfusion
trigger should be the same for both allogeneic and autologous units.

One study reviewed the postoperative course of 127 patients undergoing total knee
arthroplasty who had donated two autologous units preoperatively. Half of these patients
received their autologous blood immediately after surgery, the first unit being transfused in
the recovery room and the second on release to the floor. The remaining patients did not
receive their autologous units unless their hemoglobin fell to less than 9.0 g/dL. There were a
significantly greater number of nonsurgical complications in the conservatively treated group
(16 vs. 5) including one myocardial infarction and one cardiac dysrhythmia. The authors
concluded that a more liberal strategy was justified in this group, and speculated that the
higher rate of complications in the patients whose blood was withheld was caused by
undiagnosed cardiac disease [24].

Platelet transfusion triggers

Current investigations investigating optimal platelet therapy have focused not so much on
transfusion triggers as on the type of product required for transfusion: single-donor versus
whole blood–derived, pooled products; leukocyte-reduced versus standard products; and
HLA-matched versus crossmatched products. A recent study found that alloimmunization to
platelets substantially increases the cost and duration of hospital stay [25]. Because leukocyte
reduction substantially reduces the rate of alloimmunization (from 40–90% to 10–15%)
leukocyte reduction is recommended for any patient who will undergo a regimen of multiple
platelet transfusions. The easiest means of providing leukocyte-reduced platelets is to give
single-donor platelets, because these products are leukocyte reduced during manufacture.
Whole blood–derived, pooled platelets can be used for most surgery patients who require
platelet therapy only during the perioperative period. A recent study found that point-of-care
coagulation monitoring actually increased the use of platelets after cardiac surgery. Patients
were prospectively observed after heparin neutralization at the end of cardiopulmonary
bypass. Patients with blood loss greater than 1.5 mL/kg/15 minutes were considered to be
bleeding excessively and were randomized to one of two groups. The first received platelet
transfusion based only on clinical judgment with no recourse to laboratory values. The second
group received components based on coagulation testing. The platelet threshold was
100,000/µL. There was no difference in blood loss during the first 16 hours after transfusion,
and no difference in the total use of red cell units or hemostatic components as a whole.
However, the treatment group received more platelets. The authors concluded that a platelet
threshold of 100,000/µL was too high even with the potentially impaired platelet function
occurring after bypass, and that a lower threshold should be used [26].

Refractoriness to platelet transfusions can occur from immunologic or nonimmunologic

causes. Where immunologic incompatibility exists, either crossmatched platelets or HLA-
matched platelets can be used to provide a compatible product. Both are approximately 60%
effective, but many products chosen by either method fail to provide a good increase in
platelet count after transfusion. Petz et al. demonstrated an improved approach to platelet
therapy by identifying HLA antibodies present in the recipient and then choosing platelet
donors accordingly. The process provided equivalent results to platelet crossmatching and at
the same time increased the number of potential donors who would have been excluded as
HLA incompatible. Additionally, Petz et al. found that antibodies did not tend to broaden and
that antibody testing need only be performed monthly [27•]. Whether the method would be
improved by adding a subsequent platelet crossmatch and a search for platelet antibodies
remains to be seen [28].

Transfusion triggers for fresh frozen plasma

Fresh frozen plasma remains the stepchild in the blood bank family. The indications for its use
are vague and uncertain, and there is very little medical evidence documenting its efficacy.
Nevertheless, it remains popular with clinicians.

Recently, sterilized plasma products have become available. Solvent detergent–treated

plasma, the only licensed, sterilized product available in the United States, consists of a
pooled product (as many as 2500 individual plasma donations per lot) that is then treated with
a solvent and a detergent to kill all enveloped viruses. Non-enveloped viruses such as HAV
and parvovirus B19 are not killed by this method, and NAT testing is also performed to detect
the presence of these two viruses. Finally the product is filtered to remove white cells and
bacteria and may therefore be considered leukocyte reduced [29•,30].

Arguably, given the overuse of plasma a sterilized product should be welcome, and a few
areas of the United States have completely converted to this product [31]. Two questions
remain: are solvent detergent plasma and fresh frozen plasma comparable products, and are
there specialized clinical situations where one is superior to the other? Solvent detergent
plasma differs from fresh frozen plasma in the following ways:

Overall levels of coagulation factors are approximately 10% lower in solvent detergent–
treated plasma
levels of [alpha]-2 anti-plasmin and protein S are 40% lower, and
levels of ultra-large von Willebrand factor multimers are decreased [29•,30].

Transfusion studies performed before licensure of solvent detergent–treated plasma in both

the United States and Britain suggest that in many clinical settings the two products behave
comparably [29•,30]. A recent study evaluated solvent detergent–treated plasma versus fresh
frozen plasma in patients with prolonged prothrombin times. Patients with an acquired
coagulopathy received fresh frozen plasma or solvent detergent–treated plasma in an attempt
to reduce the prothrombin time to less than 15 seconds. Solvent detergent–treated plasma
proved comparable to fresh frozen plasma when examined for amount transfused, percentage
of patients whose prothrombin time corrected to less than 15 seconds, and percentage of
patients who stopped bleeding [32].

Although no studies exist, specialized settings where solvent detergent–treated plasma may
prove superior are in therapy for thrombotic thrombocytopenic purpura because ultra-large
VWF multimers are not infused, and, perhaps in certain situations where leukocyte depletion
is important to prevent reactions or alloimmunization. However, there are at least theoretic
risks to solvent detergent–treated plasma. Low levels of [alpha]-2 antiplasmin and protein S
may predispose to hemorrhage or thrombosis in settings where large amounts of plasma are
transfused and synthesis of these proteins is inadequate. Further, the pooling process may
predispose to transmission of non-enveloped viruses or unknown agents. Some experts
suggest that decisions regarding which product to use can be made on the projected lifetime
need for FFP. Patients who will need large volumes of plasma may be better off receiving
sterilized products because disease transmission is more likely in this setting [33].

Conclusion
Although the broad outlines of acceptable transfusion therapy are in place, much work
remains to be done to better elucidate the value of transfusion in individual clinical settings.
Better and more streamlined methods are needed to evaluate oxygen consumption and
delivery before and after red cell transfusion, especially in the setting of pre-existing coronary
artery disease. The role of red cell transfusion for patients in critical care settings also requires
further investigation. Whereas standards for prophylactic platelet therapy have been fairly
well defined in cases of failure of platelet production, more work must be done in surgical
settings or with invasive procedures, where patients have platelet counts greater than 50,000
but may have other factors predisposing them to bleeding. Certainly the one recent paper cited
suggests that at least some platelet transfusions performed in the perioperative period are
unnecessary [26]. Finally, the value of plasma components, including the role of solvent
detergent–treated plasma in transfusion medicine must be better defined. Better criteria for the
transfusion of plasma components should also be developed.

References and recommended reading

Papers of particular interest, published within the annual period
of review, have been highlighted as:
• Of special interest
•• Of outstanding interest
1. National Institutes of Health Consensus Conference: Perioperative red blood cell transfusion. JAMA 1988,
160:2700–2703. [Context Link]
2. Stehling L, Doherty DC, Faust RJ, et al.: Task force on blood component therapy: Practice guidelines for blood
component therapy: a report by the American Society of Anesthesiologists. Anesthesiology 1996, 84: 732–747. [Context
Link]

3. Simon TL, Alverson DL, AuBuchon J, et al.: Practice parameter for the use of red blood cell transfusions. Arch
Pathol Lab Med 1998, 122: 130–138. [Context Link]

4. Stehling L, Luban NLC, Anderson KC, et al.: Guidelines for blood utilization review. Transfusion 1994, 34: 438–
448. Bibliographic Links [Context Link]

5. Mallet SV, Peachey TD, Sanehi O, et al.: Reducing red blood cell transfusion in elective surgical patients: the role of
audit and practice guidelines. Anesthesia 2000, 55: 1013–1019. Buy Now Bibliographic Links [Context Link]

6. Capraro L, Nuutinen L, Myllyla: Transfusion thresholds in common elective surgical procedures in Finland. Vox
Sang 2000, 78: 96–100. Bibliographic Links [Context Link]

7. Boralessa H, Boralessa H, Contreras M et al.: Retrospective study on red cell usage in primary total knee
replacement surgery. Vox Sang 2000, 79: 231–234. Bibliographic Links [Context Link]

8. Roberts M, Ahya R, Greaves M, et al.: A one-center prospective audit of peri and postoperative blood loss and
transfusion practice in patients undergoing hip or knee replacement surgery. Ann R Coll Surg Engl 2000, 82: 44–48.
Bibliographic Links [Context Link]

9. Swain DG, Nightingale PG, Patel JV: Blood transfusion requirements in femoral neck fracture. Injury 2000, 31: 7–
10. Bibliographic Links [Context Link]

10. McFarland JG: Perioperative blood transfusions: indications and options. Chest 1999, 115 (suppl): 113–121.
[Context Link]

11.• Spahn DR: Perioperative transfusion triggers for red blood cells. Vox Sang 2000, 78 (suppl 2): 163–166. This
paper provides a good review of ongoing research in physiologic parameters that can be used as transfusion triggers.
Bibliographic Links [Context Link]

12. Hogue CW, Goodnough LT, Monk TG: Perioperative myocardial ischemic episodes are related to hematocrit level
in patients undergoing radical prostatectomy. Transfusion 1998, 38: 924–931. Bibliographic Links [Context Link]

13. Carson JL, Duff A, Poses Rm, et al.: Effect of anaemia and cardiovascular disease on surgical mortality and
morbidity. Lancet 1996, 348: 1055–1060. [Context Link]

14. Weisel RD, Charlesworth DC, Mickleborough LL, et al.: Limitations of blood conservation, J Thorac Cardiovasc
Surg 1984, 88: 26–38. [Context Link]

15.•• Hebert PC: Red cell transfusion strategies in the ICU. Vox Sang 2000, 78 (suppl 2): 167–177. This paper
discusses the largest study investigating transfusion therapy in the ICU setting. Bibliographic Links [Context Link]

16. Bracey AW, Radovancevic R, Riggs SA, et al.: Lowering the hemoglobin threshold for transfusion in coronary
artery bypass procedures: effect on patient outcome. Transfusion 1999, 39: 1070–1077. Bibliographic Links [Context Link]

17. Speiss BD, Ley C, Body SC, et al.: Hematocrit value on intensive care unit entry influences the frequency of Q-
wave myocardial infarction after coronary artery bypass grafting. J Thorac Cardiovasc Surg 1998, 116: 460–467.
Bibliographic Links [Context Link]

18. Eckardt KU: Anemia in critical illness. Wien Klin Wochenschr 2001, 113: 84–89. Bibliographic Links [Context Link]

19. Marik PE, Sibbald WJ: Effect of stored blood transfusion on oxygen delivery in patients with sepsis. JAMA 1993,
269: 3024–3029. Bibliographic Links [Context Link]

20. Hebert PC, Wells G, Marshall J, et al.: Transfusion requirements in critical care; a pilot study. JAMA 1995, 273:
1439–1444. [Context Link]
21. Hebert PC, Wells G, Blajchman MA, et al.: A multicenter, randomized controlled clinical trial of transfusion
requirements in critical care. NEJM 1999, 340: 409–417. [Context Link]

22. Vichinsky EP: Current issues with blood transfusions in sickle cell disease. Semin Hematol 2001, 38 (suppl 1): 14–
22. Bibliographic Links [Context Link]

23. Ohene-Frempong K: Indications for red cell transfusion in sickle cell disease. Semin Hematol 2001, 38 (suppl 1):
5–13. Bibliographic Links [Context Link]

24. Lotke PA, Barth P, Garino JP, et al.: Predonated autologous blood transfusions after total knee arthroplasty. J
Arthroplasty 1999, 14: 647–650. [Context Link]

25. Meehan KR, Matias CO, Rathore SS, et al.: Platelet transfusions: utilization and associated costs in a tertiary care
hospital. Am J Hematol 2000, 64: 251–256. Bibliographic Links [Context Link]

26. Capraro L, Kuitunen M, Salmenpera M, et al.: On site coagulation monitoring does not affect hemostatic outcome
after cardiac surgery. Acta Anesthesiol Scand 2001, 45: 200–206. [Context Link]

27.• Petz LD, Garratty G, Calhoun L, et al.: Selecting donors of platelets for refractory patients on the basis of HLA
antibody specificity. Transfusion 2000, 40: 1446–1456. This paper describes new strategies for selecting platelets for
refractory patients. [Context Link]

28. Kickler T: Pretransfusion testing for platelet transfusions. Transfusion 2000, 40: 1425–1426. Bibliographic Links
[Context Link]

29.• Sharma AD, Sreeram G, Erb T, et al.: Solvent detergent treated fresh frozen plasma: a superior alternative to
standard fresh frozen plasma? J Cardiothorac Vasc Anesth 2000, 14: 712–717. This paper provides a good review of
the relative advantages and disadvantages of solvent detergent–treated plasma and fresh frozen plasma. Bibliographic
Links [Context Link]

30. Pamphilon D: Viral inactivation of fresh frozen plasma. Br J Haematol 2000, 109: 680–693. Buy Now Bibliographic
Links [Context Link]

31. McCarthy LJ, Danielson CFM, Rothenberger SS, et al.: Completely converting a blood service region to the use of
safer plasma. Transfusion 2000, 40: 1264–1267. Bibliographic Links [Context Link]

32. Lerner RG, Nelson J, Sorcia E, et al.: Evaluation of solvent detergent treated plasma in patients with a prolonged
prothrombin time. Vox Sang 2000, 79: 161–167. Bibliographic Links [Context Link]

33. Bianco C: Choice of human plasma preparations for transfusion. Trans Med Rev 1999, 13: 84–88. [Context Link]

Section Description
Edited by S Gerald Sandler

Accession Number: 00062752-200111000-00012

Copyright (c) 2000-2005 Ovid Technologies, Inc.

Version: rel9.3.0, SourceID 1.10284.1.251

© 2001 Lippincott Williams & Wilkins, Inc.

 Volume 8(6) November 2001 pp 387-391

Transfusion triggers for blood components

[Transfusion medicine]

Clark, Pamela MD; Mintz, Paul D. MD

Output...
Blood Bank, Clinical Laboratories, and Department of Pathology,
University of Virginia Health System, Charlottesville, Virginia, USA.
Correspondence to Pamela Clark, MD, Blood Bank and Transfusion
Service, Box 800286, Medical Center, Charlottesville, VA 22908,
USA; e-mail: pc4b@virginia.edu

66 K

Links...

History...

Outline
 Abstract
 Red blood cells during the perioperative period
 Transfusion triggers in cardiac disease
 Transfusion triggers in critical illness
 Red cell transfusion in sickle cell disease
 Red cell transfusion using autologous blood
 Platelet transfusion triggers
 Transfusion triggers for fresh frozen plasma
 Conclusion
 References and recommended reading
 Section Description

Abstract
Whereas there are general guidelines for acceptable transfusion therapy, optimal transfusion
therapy has not been determined for most clinical settings. Recent research has focused on
controlled studies of red cell transfusion in specific clinical settings. Better determinations of
oxygen delivery and consumption are needed to guide clinicians in determining whether
transfusion is justified for patients during the perioperative period, those with coronary artery
disease, and those in intensive care units. For sickle cell disease, the role of transfusion for
acute complications can be life saving; however, the role of chronic transfusion regimens
awaits further research into efficacy. Finally, whereas criteria for the prophylactic transfusion
of platelets in hematologic diseases are well described, relatively little information is available
on the value of platelet transfusion where the absolute count is less than 100,000 but greater
than 50,000. The value of fresh frozen plasma components, both standard and sterilized, also
requires elucidation.

Current standards of acceptable transfusion practice discourage the reflexive transfusion of

blood components at specified transfusion triggers. This being said, there are general
guidelines for acceptable transfusion practice. The report of the NIH consensus conference,
published in 1988, indicated that transfusion of packed red blood cells could be justified in
most situations when the hemoglobin level declined to 7.0 g/dL [1], although more recent
guidelines have set this absolute trigger at 6.0 g/dL [2,3]. Transfusion of packed red blood cells
is almost never indicated when the hemoglobin level exceeds 10.0 g/dL, and it has been
universally condemned as unacceptable routine practice [1,2,3]. Between hemoglobin levels of
6 and 10 g/dL, however, the decision to transfuse rests on a careful, individualized
determination of the patient’s overall clinical status, taking into account any signs and
symptoms of oxygen deprivation and the potential risks and benefits of transfusion.

Similarly, platelet transfusions in a nonbleeding patient are not required until the platelet
count reaches 10,000/µL so long as the patient has no other risk factors for bleeding such as
fever, sepsis, or disseminated intravascular coagulation [2,4]. A platelet count of 50,000/µL is
generally considered acceptable for most surgical procedures [2,4], but there is little guidance
for those patients whose platelet counts are greater than 50,000 but whose clinical condition
may put them at risk for bleeding.

Guidelines for the transfusion of fresh frozen plasma are even less clear. Most transfusion
medicine specialists find the following criteria acceptable: (1) for an international normalized
ratio (INR) greater than 1.5 with anticipated invasive procedure or surgery, (2) for massive
hemorrhage (greater than one blood volume) with an INR greater than 1.5, (3) for treatment of
thrombotic thrombocytopenic purpura, (4) for inherited coagulopathies where a specific factor
concentrate is not available, and (5) for emergent reversal of anticoagulant therapy [2,4].

Although these general guidelines are useful and have prevented unnecessary transfusions,
they provide little guidance in particular clinical settings where it would be useful to know
whether a transfusion is likely to provide substantial benefit to a patient. Research on the
efficacy of transfusion in more specific clinical settings is currently ongoing. Whereas most of
this research has focused on red blood cell components, some investigations of platelet and
plasma transfusions have also been conducted recently.
Red blood cells during the perioperative period
Despite good clinical data demonstrating that hemoglobin levels as low as 6.0 or 7.0 g/dL are
well tolerated in patients without underlying cardiac or pulmonary disease, several recent
studies document that inappropriate perioperative transfusion practice continues [5–9]. At one
hospital, the main determinant of transfusion had been an estimated blood loss of greater than
500 mL. A simple guideline requiring a hemoglobin measurement before transfusion reduced
the overall number of transfusions by 43%[5]. No absolute level of hemoglobin was specified
as a trigger. Even so, this simple maneuver resulted in a marked improvement in transfusion
practice. Similarly, a nationwide multicenter study of transfusion practice in Finland
determined that inappropriate transfusion practices continued despite published guidelines [6].
Transfusions at hemoglobin levels as high as 10.7 g/dL occurred routinely, and many patients
were transfused despite loss of less than 20% of blood volume. The study concluded that
profound changes in transfusion practice were needed.

To that end, recent reviews of transfusion in the perioperative period have focused on
measurable physiologic changes in oxygen delivery and consumption that could be used to
guide transfusion practice [10,11•]. Several parameters that have been identified are oxygen
delivery, oxygen extraction, oxygen consumption, and mixed venous O 2 partial pressure.
Adequate oxygen delivery to the myocardium depends on blood flow and oxygen extraction.
Normally the heart extracts close to the maximum (approximately 50%) of the oxygen
delivered, and increasing oxygen delivery to the heart depends primarily on increasing blood
flow. Oxygen extraction greater than 50% strongly suggests that oxygen delivery is maximal
and that a transfusion is needed to prevent myocardial ischemia. Decreasing oxygen
consumption also suggests deterioration in oxygen delivery, and one review suggests that a
decrease in consumption of greater than 10% justifies transfusion [11•]. Mixed venous O 2 has
also been used as a transfusion trigger although it has been noted that this measurement may
underestimate tissue hypoxia [11•].

Transfusion triggers in cardiac disease

Anemic patients with coronary artery disease should be considered at high risk for myocardial
ischemia because they cannot increase oxygen extraction or blood flow to the heart, and there
has been some concern that anemia is particularly dangerous in this category of patients [12–
14]. Other studies have not demonstrated this phenomenon, at least in the critical care setting
[15••]. Once the lesions of coronary artery disease have been surgically corrected, however,
lower hemoglobin levels are probably preferable. In one study, length of stay, duration of
mechanical ventilation, and time in ICU were not significantly different in patients who
received transfusions for hemoglobin levels less than 8.0 g/dL as opposed to those in a control
group who were transfused per physician order [16]. Further, at least one study has found that
post-cardiopulmonary bypass patients having higher postoperative hematocrit levels are more
likely to sustain postoperative myocardial infarction [17].

Transfusion triggers in critical illness

Patients in intensive care units generally suffer from anemia [18]. Arguably, anemia in these
patients is harmful because increased oxygen delivery is needed to offset the metabolic
demands of critical illness. On the other hand, it is not clear that increasing hemoglobin
actually results in increased oxygen delivery to tissues [19]. Recent studies have attempted to
define transfusion triggers that can guide therapy for these patients [15••,20,21]. The largest
study randomized a total of 838 patients to received transfusions according to liberal and
conservative criteria. Enrolled patients were normovolemic with hemoglobin levels of 9 g/dL
or less at the time of randomization. Patients in the conservative transfusion arm were
transfused only for hemoglobin levels of less than 7 g/dL, and hemoglobin levels were
maintained between 7 and 9 g/dL. Patients in the liberal arm of the study were transfused for
hemoglobin levels of less than 10 g/dL, and their hemoglobin levels were maintained between
10 and 12 g/dL. The findings are as follows: first, there were significantly fewer transfusions
in the arm that restricted transfusions. Overall there was no increase in mortality in the
restrictive arm despite the lower hemoglobin levels sustained by these patients. Of even
greater interest, however, was that the absolute number of deaths was lower in the restrictive
arm for all patient categories and was significantly lower in some of them. The 30-day
mortality was significantly lower in patients who were less than 55 years of age or who had
Acute Physiology and Chronic Health Evaluation (APACHE) II scores of less than 20,
although overall 30-day mortality was not significantly different. Hospital mortality was also
significantly lower. There was no observed difference in mortality in patients with significant
cardiac disease. The authors concluded that a restrictive transfusion protocol with a
transfusion trigger of 7.0 g/dL decreased transfusion rates significantly and possibly improved
survival rates [15••,21].

Red cell transfusion in sickle cell disease

Two important issues must be addressed in transfusion therapy for sickle cell disease: the
actual transfusion trigger and the proper red cell component to transfuse. The lower threshold
for transfusion in sickle cell disease is difficult to determine. It is known, however, that
patients with this illness should not be transfused to hemoglobin values greater than 11 g/dL
(hematocrit no higher than 35) because of the risks of hyperviscosity. Specialized products are
indicated for the sickle cell patient. Guidelines suggest that packed red blood cells be
leukocyte reduced, hemoglobin S–negative, and at least partially phenotype specific.
Leukocyte reduction prevents most febrile, nonhemolytic transfusion reactions, which in turn
prevents unnecessary transfusion reaction work-ups that can delay needed transfusion therapy.
Ensuring that transfused units are negative for sickle hemoglobin ensures that the patient
receives maximum benefit from transfusion, because the goal of most transfusions is to
reduce the level of hemoglobin S. Further, blood containing hemoglobin S does not filter well
through leukocyte reduction filters. Finally, many blood transfusion programs phenotype red
cell units to make sure that the units are patient identical for the Ee and Kk antigens. Some
programs also include Cc. This is done because chronically transfused sickle cell patients
have high rates of alloimmunization—as many as one third of patients in some studies.
Phenotypically matched blood decreases rates of alloimmunization and is therefore
considered efficacious in this patient group [22].

Patients with sickle cell disease can be transfused in the short term to treat complications of
their disease or on a long-term basis to prevent severe complications of sickle cell disease.
Transfusion is appropriate to improve oxygen delivery in such settings as splenic
sequestration, aplastic crisis and hyperhemolysis, acute chest syndrome, stroke, severe
infection, and organ failure. Its value in treating pain crisis and priapism are still the subject of
debate. Transfusion is used to improve oxygen delivery and tissue oxygenation. However,
transfusion must be used judiciously, with careful attention to volume and viscosity so that
untoward complications do not ensue. In some cases, exchange transfusion may permit the
transfusion of a greater volume of red cells without dangerously increasing intravascular
volume [23].
Long-term transfusion regimens are usually reserved for those patients who have had severe
complications from their sickle cell disease, and transfusion is designed to prevent a
recurrence. Most commonly, long-term transfusion regimens are used to prevent recurrence of
central nervous system events. Maintaining the hemoglobin S at less than 30% has been found
to decrease the rate of stroke recurrence by 90%. More recent studies suggest that hemoglobin
S levels as high as 50% can be tolerated in patients who have been neurologically stable for
more than 3 years. Other patients who may benefit from long-term transfusion therapy are
those with recurrent acute chest syndrome, severe chronic anemia caused by concomitant
renal failure, chronic pain, and heart failure. Other uses of long-term transfusion therapy must
be considered controversial at this time [23].

Red cell transfusion using autologous blood

The transfusion trigger for autologous units has been a matter of debate. On the one hand,
autologous units do not carry with them the risk of disease transmission or immunologic
incompatibility, making a higher transfusion threshold possible. On the other hand, these units
are not risk free and are still subject to the problems of bacterial contamination, cytokine
accumulation, and clerical error. Because of these risks, many have argued that the transfusion
trigger should be the same for both allogeneic and autologous units.

One study reviewed the postoperative course of 127 patients undergoing total knee
arthroplasty who had donated two autologous units preoperatively. Half of these patients
received their autologous blood immediately after surgery, the first unit being transfused in
the recovery room and the second on release to the floor. The remaining patients did not
receive their autologous units unless their hemoglobin fell to less than 9.0 g/dL. There were a
significantly greater number of nonsurgical complications in the conservatively treated group
(16 vs. 5) including one myocardial infarction and one cardiac dysrhythmia. The authors
concluded that a more liberal strategy was justified in this group, and speculated that the
higher rate of complications in the patients whose blood was withheld was caused by
undiagnosed cardiac disease [24].

Platelet transfusion triggers

Current investigations investigating optimal platelet therapy have focused not so much on
transfusion triggers as on the type of product required for transfusion: single-donor versus
whole blood–derived, pooled products; leukocyte-reduced versus standard products; and
HLA-matched versus crossmatched products. A recent study found that alloimmunization to
platelets substantially increases the cost and duration of hospital stay [25]. Because leukocyte
reduction substantially reduces the rate of alloimmunization (from 40–90% to 10–15%)
leukocyte reduction is recommended for any patient who will undergo a regimen of multiple
platelet transfusions. The easiest means of providing leukocyte-reduced platelets is to give
single-donor platelets, because these products are leukocyte reduced during manufacture.

Whole blood–derived, pooled platelets can be used for most surgery patients who require
platelet therapy only during the perioperative period. A recent study found that point-of-care
coagulation monitoring actually increased the use of platelets after cardiac surgery. Patients
were prospectively observed after heparin neutralization at the end of cardiopulmonary
bypass. Patients with blood loss greater than 1.5 mL/kg/15 minutes were considered to be
bleeding excessively and were randomized to one of two groups. The first received platelet
transfusion based only on clinical judgment with no recourse to laboratory values. The second
group received components based on coagulation testing. The platelet threshold was
100,000/µL. There was no difference in blood loss during the first 16 hours after transfusion,
and no difference in the total use of red cell units or hemostatic components as a whole.
However, the treatment group received more platelets. The authors concluded that a platelet
threshold of 100,000/µL was too high even with the potentially impaired platelet function
occurring after bypass, and that a lower threshold should be used [26].

Refractoriness to platelet transfusions can occur from immunologic or nonimmunologic

causes. Where immunologic incompatibility exists, either crossmatched platelets or HLA-
matched platelets can be used to provide a compatible product. Both are approximately 60%
effective, but many products chosen by either method fail to provide a good increase in
platelet count after transfusion. Petz et al. demonstrated an improved approach to platelet
therapy by identifying HLA antibodies present in the recipient and then choosing platelet
donors accordingly. The process provided equivalent results to platelet crossmatching and at
the same time increased the number of potential donors who would have been excluded as
HLA incompatible. Additionally, Petz et al. found that antibodies did not tend to broaden and
that antibody testing need only be performed monthly [27•]. Whether the method would be
improved by adding a subsequent platelet crossmatch and a search for platelet antibodies
remains to be seen [28].

Transfusion triggers for fresh frozen plasma

Fresh frozen plasma remains the stepchild in the blood bank family. The indications for its use
are vague and uncertain, and there is very little medical evidence documenting its efficacy.
Nevertheless, it remains popular with clinicians.

Recently, sterilized plasma products have become available. Solvent detergent–treated

plasma, the only licensed, sterilized product available in the United States, consists of a
pooled product (as many as 2500 individual plasma donations per lot) that is then treated with
a solvent and a detergent to kill all enveloped viruses. Non-enveloped viruses such as HAV
and parvovirus B19 are not killed by this method, and NAT testing is also performed to detect
the presence of these two viruses. Finally the product is filtered to remove white cells and
bacteria and may therefore be considered leukocyte reduced [29•,30].

Arguably, given the overuse of plasma a sterilized product should be welcome, and a few
areas of the United States have completely converted to this product [31]. Two questions
remain: are solvent detergent plasma and fresh frozen plasma comparable products, and are
there specialized clinical situations where one is superior to the other? Solvent detergent
plasma differs from fresh frozen plasma in the following ways:

Overall levels of coagulation factors are approximately 10% lower in solvent detergent–
treated plasma
levels of [alpha]-2 anti-plasmin and protein S are 40% lower, and
levels of ultra-large von Willebrand factor multimers are decreased [29•,30].

Transfusion studies performed before licensure of solvent detergent–treated plasma in both

the United States and Britain suggest that in many clinical settings the two products behave
comparably [29•,30]. A recent study evaluated solvent detergent–treated plasma versus fresh
frozen plasma in patients with prolonged prothrombin times. Patients with an acquired
coagulopathy received fresh frozen plasma or solvent detergent–treated plasma in an attempt
to reduce the prothrombin time to less than 15 seconds. Solvent detergent–treated plasma
proved comparable to fresh frozen plasma when examined for amount transfused, percentage
of patients whose prothrombin time corrected to less than 15 seconds, and percentage of
patients who stopped bleeding [32].

Although no studies exist, specialized settings where solvent detergent–treated plasma may
prove superior are in therapy for thrombotic thrombocytopenic purpura because ultra-large
VWF multimers are not infused, and, perhaps in certain situations where leukocyte depletion
is important to prevent reactions or alloimmunization. However, there are at least theoretic
risks to solvent detergent–treated plasma. Low levels of [alpha]-2 antiplasmin and protein S
may predispose to hemorrhage or thrombosis in settings where large amounts of plasma are
transfused and synthesis of these proteins is inadequate. Further, the pooling process may
predispose to transmission of non-enveloped viruses or unknown agents. Some experts
suggest that decisions regarding which product to use can be made on the projected lifetime
need for FFP. Patients who will need large volumes of plasma may be better off receiving
sterilized products because disease transmission is more likely in this setting [33].

Conclusion
Although the broad outlines of acceptable transfusion therapy are in place, much work
remains to be done to better elucidate the value of transfusion in individual clinical settings.
Better and more streamlined methods are needed to evaluate oxygen consumption and
delivery before and after red cell transfusion, especially in the setting of pre-existing coronary
artery disease. The role of red cell transfusion for patients in critical care settings also requires
further investigation. Whereas standards for prophylactic platelet therapy have been fairly
well defined in cases of failure of platelet production, more work must be done in surgical
settings or with invasive procedures, where patients have platelet counts greater than 50,000
but may have other factors predisposing them to bleeding. Certainly the one recent paper cited
suggests that at least some platelet transfusions performed in the perioperative period are
unnecessary [26]. Finally, the value of plasma components, including the role of solvent
detergent–treated plasma in transfusion medicine must be better defined. Better criteria for the
transfusion of plasma components should also be developed.

References and recommended reading

Papers of particular interest, published within the annual period
of review, have been highlighted as:
• Of special interest
•• Of outstanding interest
1. National Institutes of Health Consensus Conference: Perioperative red blood cell transfusion. JAMA 1988,
160:2700–2703. [Context Link]

2. Stehling L, Doherty DC, Faust RJ, et al.: Task force on blood component therapy: Practice guidelines for blood
component therapy: a report by the American Society of Anesthesiologists. Anesthesiology 1996, 84: 732–747. [Context
Link]

3. Simon TL, Alverson DL, AuBuchon J, et al.: Practice parameter for the use of red blood cell transfusions. Arch
Pathol Lab Med 1998, 122: 130–138. [Context Link]

4. Stehling L, Luban NLC, Anderson KC, et al.: Guidelines for blood utilization review. Transfusion 1994, 34: 438–
448. Bibliographic Links [Context Link]
5. Mallet SV, Peachey TD, Sanehi O, et al.: Reducing red blood cell transfusion in elective surgical patients: the role of
audit and practice guidelines. Anesthesia 2000, 55: 1013–1019. Buy Now Bibliographic Links [Context Link]

6. Capraro L, Nuutinen L, Myllyla: Transfusion thresholds in common elective surgical procedures in Finland. Vox
Sang 2000, 78: 96–100. Bibliographic Links [Context Link]

7. Boralessa H, Boralessa H, Contreras M et al.: Retrospective study on red cell usage in primary total knee
replacement surgery. Vox Sang 2000, 79: 231–234. Bibliographic Links [Context Link]

8. Roberts M, Ahya R, Greaves M, et al.: A one-center prospective audit of peri and postoperative blood loss and
transfusion practice in patients undergoing hip or knee replacement surgery. Ann R Coll Surg Engl 2000, 82: 44–48.
Bibliographic Links [Context Link]

9. Swain DG, Nightingale PG, Patel JV: Blood transfusion requirements in femoral neck fracture. Injury 2000, 31: 7–
10. Bibliographic Links [Context Link]

10. McFarland JG: Perioperative blood transfusions: indications and options. Chest 1999, 115 (suppl): 113–121.
[Context Link]

11.• Spahn DR: Perioperative transfusion triggers for red blood cells. Vox Sang 2000, 78 (suppl 2): 163–166. This
paper provides a good review of ongoing research in physiologic parameters that can be used as transfusion triggers.
Bibliographic Links [Context Link]

12. Hogue CW, Goodnough LT, Monk TG: Perioperative myocardial ischemic episodes are related to hematocrit level
in patients undergoing radical prostatectomy. Transfusion 1998, 38: 924–931. Bibliographic Links [Context Link]

13. Carson JL, Duff A, Poses Rm, et al.: Effect of anaemia and cardiovascular disease on surgical mortality and
morbidity. Lancet 1996, 348: 1055–1060. [Context Link]

14. Weisel RD, Charlesworth DC, Mickleborough LL, et al.: Limitations of blood conservation, J Thorac Cardiovasc
Surg 1984, 88: 26–38. [Context Link]

15.•• Hebert PC: Red cell transfusion strategies in the ICU. Vox Sang 2000, 78 (suppl 2): 167–177. This paper
discusses the largest study investigating transfusion therapy in the ICU setting. Bibliographic Links [Context Link]

16. Bracey AW, Radovancevic R, Riggs SA, et al.: Lowering the hemoglobin threshold for transfusion in coronary
artery bypass procedures: effect on patient outcome. Transfusion 1999, 39: 1070–1077. Bibliographic Links [Context Link]

17. Speiss BD, Ley C, Body SC, et al.: Hematocrit value on intensive care unit entry influences the frequency of Q-
wave myocardial infarction after coronary artery bypass grafting. J Thorac Cardiovasc Surg 1998, 116: 460–467.
Bibliographic Links [Context Link]

18. Eckardt KU: Anemia in critical illness. Wien Klin Wochenschr 2001, 113: 84–89. Bibliographic Links [Context Link]

19. Marik PE, Sibbald WJ: Effect of stored blood transfusion on oxygen delivery in patients with sepsis. JAMA 1993,
269: 3024–3029. Bibliographic Links [Context Link]

20. Hebert PC, Wells G, Marshall J, et al.: Transfusion requirements in critical care; a pilot study. JAMA 1995, 273:
1439–1444. [Context Link]

21. Hebert PC, Wells G, Blajchman MA, et al.: A multicenter, randomized controlled clinical trial of transfusion
requirements in critical care. NEJM 1999, 340: 409–417. [Context Link]

22. Vichinsky EP: Current issues with blood transfusions in sickle cell disease. Semin Hematol 2001, 38 (suppl 1): 14–
22. Bibliographic Links [Context Link]

23. Ohene-Frempong K: Indications for red cell transfusion in sickle cell disease. Semin Hematol 2001, 38 (suppl 1):
5–13. Bibliographic Links [Context Link]
24. Lotke PA, Barth P, Garino JP, et al.: Predonated autologous blood transfusions after total knee arthroplasty. J
Arthroplasty 1999, 14: 647–650. [Context Link]

25. Meehan KR, Matias CO, Rathore SS, et al.: Platelet transfusions: utilization and associated costs in a tertiary care
hospital. Am J Hematol 2000, 64: 251–256. Bibliographic Links [Context Link]

26. Capraro L, Kuitunen M, Salmenpera M, et al.: On site coagulation monitoring does not affect hemostatic outcome
after cardiac surgery. Acta Anesthesiol Scand 2001, 45: 200–206. [Context Link]

27.• Petz LD, Garratty G, Calhoun L, et al.: Selecting donors of platelets for refractory patients on the basis of HLA
antibody specificity. Transfusion 2000, 40: 1446–1456. This paper describes new strategies for selecting platelets for
refractory patients. [Context Link]

28. Kickler T: Pretransfusion testing for platelet transfusions. Transfusion 2000, 40: 1425–1426. Bibliographic Links
[Context Link]

29.• Sharma AD, Sreeram G, Erb T, et al.: Solvent detergent treated fresh frozen plasma: a superior alternative to
standard fresh frozen plasma? J Cardiothorac Vasc Anesth 2000, 14: 712–717. This paper provides a good review of
the relative advantages and disadvantages of solvent detergent–treated plasma and fresh frozen plasma. Bibliographic
Links [Context Link]

30. Pamphilon D: Viral inactivation of fresh frozen plasma. Br J Haematol 2000, 109: 680–693. Buy Now Bibliographic
Links [Context Link]

31. McCarthy LJ, Danielson CFM, Rothenberger SS, et al.: Completely converting a blood service region to the use of
safer plasma. Transfusion 2000, 40: 1264–1267. Bibliographic Links [Context Link]

32. Lerner RG, Nelson J, Sorcia E, et al.: Evaluation of solvent detergent treated plasma in patients with a prolonged
prothrombin time. Vox Sang 2000, 79: 161–167. Bibliographic Links [Context Link]

33. Bianco C: Choice of human plasma preparations for transfusion. Trans Med Rev 1999, 13: 84–88. [Context Link]

Section Description
Edited by S Gerald Sandler

Accession Number: 00062752-200111000-00012

Copyright (c) 2000-2005 Ovid Technologies, Inc.

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