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A transfusion medicine physician in Massachusetts would like to know what policies institutions follow regarding avoiding the transfusion of ABO-incompatible plasma (such as might happen when giving group A platelets to a group AB recipient) to patients who have received ABO-compatible allogeneic bone marrow transplants. He adds that while there can be risks associated with transfusion of ABO-incompatible plasma for non-transplant patients, and there are increased risks with transfusing transplant patients receiving ABO-incompatible transplants, he is wondering whether patients receiving ABO-compatible transplants might fall into an intermediate risk category. It is his opinion that unlike other transplant patients, these patients do not have ABO antibodies produced by their original immune system that react against the donor marrow. However, transfusing incompatible antibodies might react with a marrow that is just engrafting and also bind to endothelial cells and other cells in a patient who is being treated with high doses of chemotherapy. Hence, he wonders if there may be reason to volume reduce ABO-incompatible plasma in cellular products intended for these patients, or avoid such transfusions altogether. Finally, he wonders if these considerations might also apply to autologous marrow transplant patients. ADDENDA Nov. 18 , 2004 The following responses have been received. 1. According to Joanna M. Heal MBBS MRCP and Neil Blumberg MD at the University of Rochester (attribution used with permission), they have not seen clinically evident cases of hemolysis after transfusion of incompatible platelets in recent years, as >90% of their platelet transfusions are ABO identical, and they only rarely administer group O platelets to non-O recipients, for the reasons discussed below. In years before 1990, when they routinely administered ABO mismatched platelets, they frequently observed patients with positive direct antiglobulin tests, increased red cell transfusion needs and other evidence of hemolysis. For unavoidably ABO mismatched platelet transfusions, as in patients receiving HLA- or HPA-matched platelets, they wash before transfusing to remove the incompatible supernatant plasma antigen and antibody. While some might think this plasma reduction is unnecessary, they are increasingly convinced that administration of large amounts of incompatible anti-A and anti-B, or soluble A and B antigens, may have deleterious effects on many patients that are not obvious. (reference 1) Some clinical events that they hypothesize are due to transfusion of ABO incompatible plasma and cells are not as easily attributable to the transfusion as post-transfusion hemolysis. For example, transfusion of ABO mismatched platelets increases the risk of HLA alloimmunization and platelet refractoriness in the two small randomized trials addressing this issue.(references 2 and 3) Transfusion of incompatible plasma leads to large quantities of circulating high molecular weight, long-lived immune complexes. These immune complexes fix complement, bind to platelets, leading to phagocytosis by monocytes, and carry unknown potential for morbidity.(reference 4) Such morbidity speculatively could include interference with anti-leukemia cellular immunity (reference 5) or a pro-inflammatory predisposition to multi-organ failure and death in cardiac surgery (reference 6). The assumption that the sole biologic and clinical effect of transfused anti-A and anti-B is to cause destruction of circulating red cells seems improbable to them. ABH antigens are present in the recipient in soluble form, on endothelial cells, white cells and virtually every other cell in the body. Transfusion of incompatible soluble A and B antigens may likewise not be benign. They attempt to transfuse only ABO identical platelets, particularly to patients receiving repeated platelet transfusions. When non-ABO identical platelets must be administered due to shortages or changing ABO blood groups in allogeneic stem cell transplant recipients, they routinely transfuse saline resuspended, machine washed O platelets preferentially. There are minimal amounts of incompatible cells, soluble antigen and antibody in this transfused component. They also sometimes decrease the number of transfused whole blood platelet concentrates from a routine pool of 5 units to 3 or 4 so that only ABO identical transfusions are administered. They do not use titres to select mismatched platelets because they believe this method is unreliable at predicting biologic and clinical effects in the recipient. They are concerned that employing titers of incompatible ABO antibodies to select “safe” donors may represent treating themselves rather than effectively treating the patient, given the lack of data supporting the predictive value of titres. They are also of the opinion that the use of the term “compatible,” derived from red cell transfusions that are relatively plasma poor, should not be applied to platelet transfusions that contain an order of magnitude greater amounts of plasma soluble antigen and antibody. Platelet transfusions are more analogous to whole blood transfusions in this regard, and in the modern era, ABO non-identical whole blood would rarely or never be considered suitable for transfusion. Unless plasma-reduced, they believe platelet transfusions should ideally be ABO identical. In their center, thrombocytopenic patients with hematologic diseases are transfused solely with ABO identical or washed, platelet antigen and antibody identical platelet concentrates. They will administer a reduced dose of whole blood derived platelet concentrates (e.g., a pool of 4 rather than 5) rather than give incompatible plasma or platelets to the patient. They also transfuse solely ABO identical platelets to patients with ventricular assist devices who are awaiting cardiac transplantation, because their platelet transfusion needs are considerable over a period of days to weeks, somewhat analogous to patients with hematologic diseases. For all other patients they attempt to give only ABO identical platelets, but occasionally no such platelets are available. Then they will transfuse unwashed ABO mismatched platelets. This happens most commonly in emergency transfusions for massive hemorrhage in trauma or liver transplantation. There is no time for washing or plasma reduction by centrifugation in this setting. This happens in fewer than 5-10% of transfusions in their institution. References:
ADDENDA Nov. 19, 2004 2. A transfusion medicine physician at an academic medical center in Seattle reports that it is their policy to avoid incompatible plasma being transfused to any patient who has received a stem cell transplant, autologous or allogeneic, incompatible or not. They believe that the data for avoiding incompatible plasma for the ABO mismatched transplants are actually not that compelling, but a randomized control trial may not be possible because of the numbers that would be needed to see a difference in time to engraftment and survival, as well as the many confounding influences that would be encountered in a multicenter trial. Although there is platelet loss and some damage (reversibility unknown) with volume reduction, they continue to see good platelet increments and no discernible association with increased bleeding. The reason they do not want to administer incompatible plasma is to avoid the hypothetical risk that an antibody could affect maturing erythrocytes. Because of difficulties in having transfusing nurses understand differences between apheresis and pooled platelets and why a group O platelet transfusion might be alright for a group B patient but not for a group A patient, they do volume reduction with all plasma-incompatible platelet products. They also issue a daily report for the nurse that outlines each patient's needs including acceptable ABO types for RBC and platelet transfusions, as well as attributes such as leukoreduction. The transfusing nurse is the 'last check' they have to ensure that the patient is receiving an appropriate component. Many centers choose to limit the amount of incompatible plasma a patient can receive on a daily or weekly basis. They believe this would be too difficult for them to monitor. |
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Please submit comments to the e-Network Forum. Ira A. Shulman, MD |
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Posted: November 17, 2004
Addenda: Nov. 18 & 19, 2004 |
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