Transfusion Of ABO-incompatible Plasma Research Articles

Risk of ABO-Incompatible Plasma From Non-ABO-Identical Components.

The last several decades have seen significant changes in the approach to resuscitation of bleeding patients. These include the adoption of ABO-incompatible plasma transfusion in the form of group A plasma and/or low titer group O whole blood for trauma patients of unknown ABO group. Studies to date have examined the impact of these practices on patient outcomes and clinical markers of hemolysis in recipients of ABO-incompatible plasma compared to those for whom the plasma is ABO-compatible. Risk for increased mortality and/or overt hemolysis appear to be low among recipients of ABO-incompatible plasma; however, nearly all of studies are retrospective and most have focused only on adult trauma patients so results may not be generalizable to other bleeding patients. Work continues to evaluate the role of various titer thresholds in decreasing hemolytic risk and opportunities remain to improve our understanding of anti-A and anti-B antibody interactions with complement/endothelium and identify strategies to minimize risk.

Evaluation of A plasma for incompatible patients.

Plasma transfusion is a critical treatment in managing bleeding patients. In an effort to make plasma immediately available in spite of the limited amount of AB plasma, providers have begun using A plasma in life-threatening emergencies. As this practice becomes widely adopted it is important to evaluate safety. Hemolytic transfusions reactions are underreported, and hemolysis may be subclinical. A retrospective study was performed at the University of Florida/Shands Hospital of B and AB patients who received 1 unit or more of A plasma. Patient charts were reviewed and data collected included age; sex; mortality; intensive care unit (ICU) length of stay; and laboratory tests used in identifying hemolysis including direct antiglobulin test, lactate dehydrogenase, haptoglobin, indirect bilirubin, aspartate aminotransferase, urinalysis, hemoglobin, and hematocrit. The primary end points of the study were immune mediated hemolysis, mortality, and length of ICU stay. Ninety-three patients were identified as eligible for the study. One patient suffered a delayed hemolytic transfusion reaction determined to be due to an anti-Jka . No evidence of hemolysis due to ABO-incompatible plasma transfusion was identified. The volume of A plasma transfused was found to be weakly related to mortality and ICU stay. No evidence of ABO immune-mediated hemolysis was observed in the patient population. The results of the study support the safety of A plasma transfusion in B and AB patients. We hypothesize the relationship observed between A plasma volume and mortality/ICU stay may be from collinearity with disease severity.

Risks of hemolysis due to anti‐A and anti‐B caused by the transfusion of blood or blood components containing ABO‐incompatible plasma

The increasing use of fresh blood group O whole blood in acute trauma medicine makes it important to reevaluate the issue of hemolytic reactions related to the transfusion of ABO-incompatible plasma. This review summarizes and evaluates published articles and case reports concerning hemolytic reactions in connection with the transfusion of group O whole blood or blood products to nongroup O recipients. In 1945-1986, 15 nonmilitary publications reported hemolytic transfusion reactions with group O blood/blood products. All patients recovered except for two fatalities. Late in World War II and during the Korean and Vietnam wars and onward in Iraq and Afghanistan only "low anti-A, anti-B titer" group O whole blood has been used as universal blood. In spite of a large number of units transfused, there are no reports of hemolytic reactions. Twenty-five publications report hemolytic reactions after transfusion of group O platelets to nongroup O recipients. In all patients but one, the titer of the implicated A- or B-antibody was >100 (saline) or >400 (antiglobulin) and all cases with an infused volume of incompatible plasma <200 mL were related to anti-A or anti-B antiglobulin titers >1000. In emergency lifesaving resuscitation, the risk of hemolytic transfusion reactions from transfusion of group O blood to nongroup O recipients constitutes risk that is outweighed by the benefits. A low titer of anti-A/B will minimize the risk for a hemolytic reaction, particularly if the screening is repeated after an immunization episode, e.g., blood transfusion, vaccination, or pregnancy.

Titers of ABO antibodies in group O blood donors

Overt hemolysis from the transfusion of ABO incompatible plasma containing high titer anti-A or anti-B is a rare event. Plasma from group O donors and the transfusion of single donor platelets are most often associated with these reactions when transfused to group A or AB recipients. Several studies over the years have evaluated donor ABO antibody class, titer, and subclass in an effort to understand the breadth of the problem and reduce or eliminate this potentially serious immune complication of transfusion. In this regard, de Franca et al.(1) in this issue of the Revista Brasileira de Hematologia e Hemoterapia underscore the lack of a national standard of practice to guide the transfusion of incompatible ABO plasma transfusions. They point out that seminal work, started more than 2 decades ago, has yet to set policy and safety guidelines with the use of plasma that potentially contain life-threatening levels of anti-A or anti-B.(2) de Franca et al. examined over 5% of their blood donors included males and females across all age groups in an effort to understand which donors pose the biggest risk for the transfusion of high-titer anti-A or anti-B. Not surprising they found that ABO antibody titers decrease with age, with older males having the lowest titers by age 50. Cumulatively, nearly 1 in 10 plasma contain anti-A titers ≥ 128. Their work suggests that targeting ABO incompatible plasma and platelets from older males would lower the risk, if one assumes titers over 64 by the doublingdilution method (generally titers = 100 are regarded as critical) pose significant risk of hemolysis. However, there is still a 1:20 (5.3%) chance that plasma from males over 50 will contain a titer ≥ 128. Thus, targeting sex and specific age groups as surrogate markers for the transfusion of ABO incompatible platelets could hardly be considered safe practice, although it would be a step in the right direction. The lack of a standardized test and the impact on blood product availability is having an effect on the ability to drive policy and develop meaningful guidelines. Methodology appears to be a major issue. de Franca et al. used direct agglutination, however, other studies have used a test tube indirect antiglobulin test (IAT), gel microcolumn agglutination in an IAT, and flow cytometry to measure the amount of anti-A,B, anti-A and anti-B. The measurement of anti-A,B does not appear to provide any additional information on titers when compared to anti-A (de Franca et al.(1) Table 1). One problem with defining a standard may be the lack of studies necessary to correlation these methods and thus an agreement on the critical titer for which non-ABO matched platelet transfusions should be avoided. European blood centers have addressed the issue of titers and have identified low-risk titers for ABO incompatible plasma transfusions. It is important to establish critical ABO antibody titers by population (national), using the most clinically relevant method, since it appears that diet and ethnicity may result in significant differences in titers.(3,4) Performing population estimates for anti-A and anti-B levels across blood donors determines the frequency of high titers and help estimate the cost of implementing a nationalized testing policy. de Franca et al. have made a significant contribution in this regard. However, the challenge remains to quantify the impact that such a policy will have on the provision of plasma containing platelet products to recipients.(5)

ABO and platelet transfusion revisited

Historically, ABO compatibility between donor and recipient has been considered of minor importance for platelet transfusion. However, in a recent randomized trial we showed that provision of only ABO-identical platelets was associated with a significantly higher corrected count increment (CCI) in the early transfusions and with a twofold reduction in refractoriness, as compared with platelets given unmatched for ABO. In older studies this phenomenon was not observed. We wondered whether in these previous studies the use of the conventional term "ABO compatible", whereby ABO-identical platelet transfusions are grouped with those that are merely ABO compatible, might have obscured the advantages of the ABO-identical platelets. In this paper the CCI from our original study are compared with what would have been found had the conventional terminology of "ABO compatible" and "ABO incompatible" been used. In our original study the mean CCI in patients receiving only ABO-identical platelets was 64% higher than that achieved with ABO-unmatched products. However, when the transfusions were reanalyzed according to conventional terminology of ABO "compatible" and "incompatible," the actual benefits of ABO-identical platelets were no longer detected. Thus, had we used the conventional terminology in the original study we would have come to completely different conclusions about the importance of ABO in platelet transfusion. We hypothesize that transfusion of ABO-incompatible plasma leads to the formation of immune complexes that can destroy compatible platelets by indirect mechanisms. This model predicts that the success of a transfusion could be affected by previous incompatible transfusions. When transfusions were classified as to whether they were first, second, or third unmatched transfusion, increasing numbers of transfusions of ABO-incompatible plasma were associated with progressively poorer mean increments. The same was true for platelet ABO-incompatible transfusions. In contrast, increasing numbers of ABO-identical transfusions were not associated with poorer increments. The failure to appreciate that (a) transfusions containing ABO-incompatible plasma yield poor increments and (b) the effects of ABO-nonidentical transfusions are cumulative, and therefore affect the success of subsequent identical transfusions, may have led in the past to the incorrect conclusion that ABO matching was of minor importance in repetitively transfused patients.