Platelet ABO matters

TransfusionVolume 49, Issue 1 p. 5-7 Free Access Platelet ABO matters Richard M. Kaufman MD, Richard M. Kaufman MD e-mail: rmkaufman@partners.orgPathology DepartmentBlood BankBrigham and Women's HospitalBoston, MASearch for more papers by this author Richard M. Kaufman MD, Richard M. Kaufman MD e-mail: rmkaufman@partners.orgPathology DepartmentBlood BankBrigham and Women's HospitalBoston, MASearch for more papers by this author First published: 23 December 2008 https://doi.org/10.1111/j.1537-2995.2008.02011.xCitations: 7AboutSectionsPDF ToolsRequest permissionExport citationAdd to favoritesTrack citation ShareShare Give accessShare full text accessShare full-text accessPlease review our Terms and Conditions of Use and check box below to share full-text version of article.I have read and accept the Wiley Online Library Terms and Conditions of UseShareable LinkUse the link below to share a full-text version of this article with your friends and colleagues. Learn more.Copy URL Share a linkShare onFacebookTwitterLinkedInRedditWechat Investigators in the 1950s discovered that A and B antigens are present on platelet (PLT) membranes.1 In 1965, Aster2 demonstrated that transfused ABO major-incompatible PLTs (e.g., group A1 donor PLTs into a group O recipient) are recovered in the recipient's circulation at lower levels than ABO-identical PLTs. Aster's radiolabeling experiments suggested that a sizable fraction of transfused ABO major-incompatible PLTs were cleared within 10 minutes, too quickly to be attributed to routine splenic sequestration. PLTs surviving the initial wave of elimination circulated normally, for up to 8 days. In the late 1980s to early 1990s, two small randomized clinical trials of ABO-identical versus ABO-incompatible PLTs in adult recipients confirmed that PLT recovery is reduced when ABO-incompatible PLTs are transfused.3,4 A secondary analysis of data from the TRAP study also showed that ABO compatibility is an important determinant of posttransfusion increment.5 Nevertheless, to this day, ABO type is often disregarded by blood banks when issuing PLTs, because of inventory considerations . . . or perhaps because of a lack of appreciation of the clinical importance of PLT ABO compatibility. ABH antigen is intrinsic to PLT membranes. Most is expressed on PLT glycoprotein (GP)IIb/IIIa.6 Detailed studies by Cooling and colleagues7,8 proved that the expression of A antigen on PLTs is linked to the A1 red blood cell (RBC) phenotype. On average, approximately 40 percent of an A1 donor's PLTs express detectable A antigen. The size of the A antigen–expressing PLT fraction varies widely among A1 individuals, however. Group A2 PLTs do not express significant amounts of A antigen and are fully compatible with group O recipients.7 In this issue of TRANSFUSION, Julmy and colleagues9 report the results of a single-institution prospective trial examining the effect of PLT ABO incompatibility on PLT increments in thrombocytopenic children. This was not a randomized trial. Rather, clinical and laboratory data were gathered prospectively on consecutive pediatric hematology-oncology patients requiring PLT transfusion. Apheresis PLTs were issued by the blood bank according to local policy: older PLT units were issued first to help prevent outdating. ABO-identical PLTs were issued when available; otherwise ABO major- or minor-incompatible units were provided. The primary endpoint was the 1-hour percent PLT recovery (PPR1hr) in ABO-mismatched versus ABO-identical PLT transfusions. Four hundred PLT transfusions administered to 50 children were evaluated. The median PLT increment was 34 percent lower for 76 ABO major-incompatible PLT transfusions than for 282 ABO-identical transfusions (median PPR1hr, 21% vs. 32%, p = 0.034). A1 major-incompatible PLT transfusions fared the worst compared with ABO-identical transfusions (median PPR1hr, 18% vs. 32%, p = 0.007). In contrast, A2 major-incompatible PLTs and ABO minor-incompatible PLTs provided increments that were very similar to ABO-identical PLTs. Rapid clearance of A antigen-expressing PLTs transfused to group O or B recipients was demonstrated by flow cytometry. Limitations of the study by Julmy and colleagues9 include the nonrandomized study design and the fact that a clinical (bleeding) endpoint was not used. Overall though, this is a large, well-done study that convincingly confirms earlier observations. The authors note that theirs is the first study of PLT ABO compatibility to be conducted in pediatric patients in the era of apheresis PLTs. Indeed, this study overturns the verdict of a 1978 study10 which showed no effect of PLT ABO incompatibility on transfusion outcomes in children. That said, it should not be surprising that major ABO incompatibility negatively impacts PLT increments in pediatric recipients, as anti-A/B antibody titers in children typically reach adult levels by age 5 to 10.11 Decreased PLT recovery after transfusion is not the only problem with ABO-incompatible PLTs—and it might not even be the most important problem. In ABO minor-incompatible PLT transfusions, anti-A/B is passively transfused, which in rare instances causes acute hemolysis in the recipient. In some cases, renal failure and even death has resulted. Hemolytic reactions from ABO-incompatible PLTs are essentially always caused by type O PLT units, with the recipients being group A (most common), B, or AB.8,12,13 Dilution of donor ABO antibody in the recipient's plasma is thought to mitigate against hemolysis. Second, transfused antibody can bind to non-RBC A or B substance, present either on tissue endothelial cells or soluble in the recipient's plasma.14 Transfusing large volumes of ABO-incompatible plasma, particularly to recipients with small plasma volumes (i.e., pediatric patients), increases the risk of hemolysis.13,15 Because apheresis PLTs are derived from a single donor, they may carry a higher risk for causing hemolysis than pooled whole blood–derived PLT concentrates. A typical anti-A titer in an adult is approximately 128.16 In most reported cases of hemolysis, although not all, the PLT donor's anti-A titer is significantly elevated, sometimes titering out to 10,000 or more by indirect antiglobulin test.7,12,13 No international consensus exists at this time on how to deal with the risk of hemolysis from passively transfused ABO antibody.12 AABB Standard 5.14.4 simply states that transfusion services "shall have a policy concerning transfusion of components containing significant amounts of incompatible ABO antibodies [or unexpected red cell antibodies]."17 One strategy is to screen PLT units for high-titer ABO antibody. In the United Kingdom, all PLT donations, independent of ABO type, undergo automated screening for anti-A/B using a critical titer of 1:100. This approach identifies approximately 10 percent of donations as "high-titer"; these units are ordinarily restricted to ABO-identical recipients.13 In contrast, less than 2 percent of 3156 US centers surveyed recently reported screening PLT units for ABO antibodies.12 Among those that do screen, there is disagreement on what method should be used and what constitutes a critical titer. Alternate strategies involve reducing the volume of ABO-incompatible plasma transfused. Some centers limit the volume of out-of-group plasma that may be transfused per a designated time period; other facilities remove ABO-incompatible plasma from PLT units.12 (In Europe, a PLT additive solution often replaces much of the plasma.) Rarely, the volume-reduction approach has failed in cases where the PLT donor has an unusually high anti-A titer.18 ABO-incompatible PLT transfusions have been associated with numerous other problems. Passive A/B antibody transfusion is of particular concern in the setting of ABO-mismatched stem cell transplants. For example, it is recommended to avoid transfusing plasma products containing anti-A to the recipient of a group A stem cell transplant, so as not to impair erythropoietic reconstitution.15 ABO-incompatible PLT transfusions have also been linked to hepatic venoocclusive disease19 and mortality20 among stem cell transplant recipients. Finally, ABO-incompatible PLTs have been reported to be associated with immune complex formation,21 PLT alloimmunization/refractoriness,22-24 and adverse clinical outcomes among cardiac surgery patients.25 Currently, the vast majority of PLT transfusions are given as prophylaxis to nonbleeding patients with thrombocytopenia. The recently completed PLADO study26,27 proved that the risk of bleeding does not change when low-dose prophylactic PLTs are administered instead of standard-dose (or even high-dose) PLTs. Thus it is tempting to speculate that a lower PLT increment caused by ABO incompatibility might not alter the likelihood that a nonbleeding patient will bleed. Conversely, if low-dose PLT prophylaxis became the norm, it is conceivable that ABO effects could assume greater clinical significance. For patients with active bleeding, it would be nearly impossible to prove that a poor increment from an ABO-incompatible PLT transfusion affected outcome, but in this setting, it would only seem appropriate to provide PLTs that have a better chance of circulating as intended. ABO minor-incompatible PLT transfusions are a rare cause of acute hemolysis. Current approaches to this problem range from ignoring it to performing routine antibody screening on a national scale.12,13 Future studies may help better define the scope of this problem and the utility of preventative measures. In the meantime, now may be an appropriate time to reevaluate the current AABB standards related to PLT transfusions and ABO, with the goal of maximizing the benefits and minimizing the risks for our patients. It might also be appropriate to update clinical practice guidelines to emphasize that PLT ABO incompatibility—major or minor—should be avoided whenever possible. REFERENCES 1 Gurevitch J, Nelken D. ABO groups in blood platelets. J Lab Clin Med 1954; 44: 562- 70. 2 Aster RH. Effect of anticoagulant and ABO incompatibility on recovery of transfused human platelets. Blood 1965; 26: 732- 43. 3 Lee EJ, Schiffer CA. ABO compatibility can influence the results of platelet transfusion. Results of a randomized trial. Transfusion 1989; 29: 384- 9. 4 Heal JM, Rowe JM, McMican A, Masel D, Finke C, Blumberg N. The role of ABO matching in platelet transfusion. Eur J Haematol 1993; 50: 110- 7. 5 Slichter SJ, Davis K, Enright H, Braine H, Gernsheimer T, Kao KJ, Kickler T, Lee E, McFarland J, McCullough J, Rodey G, Schiffer CA, Woodson R. Factors affecting posttransfusion platelet increments, platelet refractoriness, and platelet transfusion intervals in thrombocytopenic patients. Blood 2005; 105: 4106- 14. 6 Santoso S, Kiefel V, Mueller-Eckhardt C. Blood group A and B determinants are expressed on platelet glycoproteins IIa, IIIa, and Ib. Thromb Haemost 1991; 65: 196- 201. 7 Cooling LL, Kelly K, Barton J, Hwang D, Koerner TA, Olson JD. Determinants of ABH expression on human blood platelets. Blood 2005; 105: 3356- 64. 8 Cooling L. ABO and platelet transfusion therapy. Immunohematology 2007; 23: 20- 33. 9 Julmy F, Ammann RA, Mansouri Taleghani B, Fontana S, Hirt A, Leibundgut K. Transfusion efficacy of ABO major-mismatched platelets (PLTs) in children is inferior to that of ABO-identical PLTs. Transfusion 2009; 49: 21- 33. 10 Van Eys J, Thomas D, Olivos B. Platelet use in pediatric oncology: a review of 393 transfusions. Transfusion 1978; 18: 169- 73. 11 Auf der Maur C, Hodel M, Nydegger UE, Rieben R. Age dependency of ABO histo-blood group antibodies: reexamination of an old dogma. Transfusion 1993; 33: 915- 8. 12 Fung MK, Downes KA, Shulman IA. Transfusion of platelets containing ABO-incompatible plasma: a survey of 3156 North American laboratories. Arch Pathol Lab Med 2007; 131: 909- 16. 13 National Blood Service. Clinical Guidelines and Advice Internal. Red Cell Transfusion and Red Cell Immunohaematology. High titre anti-A/B testing of donors within the national blood service (NBS) [monograph on the internet]. London: NBS; 2006. Available from: http://hospital.blood.co.uk/library/clinical_guidelines_and_advice_internal/index.asp 14 Harris SB, Josephson CD, Kost CB, Hillyer CD. 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Transplantation 2005; 80: 314- 9. 20 Benjamin RJ, Antin JH. ABO-incompatible bone marrow transplantation: the transfusion of incompatible plasma may exacerbate regimen-related toxicity. Transfusion 1999; 39: 1273- 4. 21 Heal JM, Masel D, Rowe JM, Blumberg N. Circulating immune complexes involving the ABO system after platelet transfusion. Br J Haematol 1993; 85: 566- 72. 22 Brand A, Sintnicolaas K, Claas FH, Eernisse JG. ABH antibodies causing platelet transfusion refractoriness. Transfusion 1986; 26: 463- 6. 23 Carr R, Hutton JL, Jenkins JA, Lucas GF, Amphlett NW. Transfusion of ABO-mismatched platelets leads to early platelet refractoriness. Br J Haematol 1990; 75: 408- 13. 24 Heal JM, Liesveld JL, Phillips GL, Blumberg N. What would Karl Landsteiner do? The ABO blood group and stem cell transplantation. Bone Marrow Transplant 2005; 36: 747- 55. 25 Blumberg N, Heal JM, Hicks GL Jr, Risher WH. Association of ABO-mismatched platelet transfusions with morbidity and mortality in cardiac surgery. Transfusion 2001; 41: 790- 3. 26 Blood. ASH Annual Meeting Abstracts. 2008 American Society of Hematology annual meeting abstracts. Washington, DC: Blood; 2008. Available from: http://bloodjournal.hematologylibrary.org/misc/ASH_Meeting_Abstracts_Info.dtl 27 Slichter SJ. Background, rationale, and design of a clinical trial to assess the effects of platelet dose on bleeding risk in thrombocytopenic patients. J Clin Apher 2006; 21: 78- 84. Citing Literature Volume49, Issue1January 2009Pages 5-7 ReferencesRelatedInformation