EDITORIAL ABO matching of platelet transfusions - "Start Making Sense" "As we get older, and stop making sense…" - The Talking Heads (1984) Neil Blumberg, Majed Refaai, Joanna Heal Department of Pathology and Laboratory Medicine, University of Rochester Medical Center, Rochester, NY, United States of America
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plasma? We treat plasma differently when it is in platelet transfusions than when it is in whole blood or fresh-frozen plasma. Somewhere along the way, as a specialty, we never fully considered the bewildering paradox of such diametrically opposed clinical practices. Which approach makes sense? If we can in good conscience transfuse litres of ABO incompatible plasma with platelets, should we not do the same for fresh-frozen plasma and whole blood? If not, why are we zealously avoiding transfusing litres of incompatible plasma and plasma in whole blood, but entirely comfortable doing so with platelets? In this issue of Blood Transfusion, Pilar Solves and colleagues report on the clinical outcome of recipients of autologous stem cell transplants who received, largely due to chance and availability, either ABO identical, ABO non-identical or both of these types of platelet transfusions14. They found that patients who received solely ABO identical or solely ABO non-identical
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The subject of ABO matching of platelet transfusions is one that generates widely varying opinions among transfusion medicine specialists1. That might seem odd, given that our knowledge of the ABO blood group has had 115 years to accumulate. But here is the reality. Transfusion Medicine services transfuse small amounts of ABO incompatible plasma (perhaps 20-40 mL in most cases) with red cells (i.e., so-called universal donor group O). But we never, ever, if we can help it, transfuse group O plasma or whole blood to patients other than O recipients, due to the 200-300 mL of incompatible plasma present. On the other hand, it is entirely acceptable practice in many centres to transfuse 200-300 mL of incompatible group O plasma to non-O recipients when platelets are transfused. Sometimes platelets are transfused daily, for weeks on end, in patients who have undergone ablative chemotherapy for leukaemia or stem cell transplantation. Does this disparity make sense from a scientific or clinical standpoint? Transfusion of ABO incompatible plasma in platelet concentrates causes varying degrees of haemolysis in the recipient, typically resulting in a positive direct antiglobulin test, or, on very rare occasions, haemolysis so severe that it is fatal2-4. Transfused or transplacental ABO incompatible antibody can also bind to and injure endothelial cells5. Transfusion of ABO incompatible, platelet-surface and plasma-soluble ABO antigen in platelet concentrates leads to formation of high molecular weight immune complexes in the recipient6,7. The consequences are not fully known, but include, at minimum, increased rates of platelet destruction and transfusion refractoriness (see Table I)8-10. Immune complexes could, speculatively, lead to inflammation and thrombocytopenia with bleeding 11, neutrophil activation12, organ injury, and immune modulation13 of the transfusion recipient. Commonly employed platelet transfusion practices allowing multiple, ABO plasma incompatible transfusions may be convenient for transfusion services. This approach may also be rationally justifiable on the basis of logistics or availability. Nonetheless, why hasn't our specialty started making scientific and clinical sense when it comes to two incompatible (pun intended) practices involving transfusion of incompatible
Table I - Haemolysis and immune complex formation in platelet transfusion recipients according to donor and recipient ABO blood groups. Platelet donor ABO group
O
A
B
AB
Platelet recipient ABO group
Potential for haemolysis
Potential for circulating immune complexes
A
Yes
Yes
B
Yes
Yes
AB
Yes
Yes
O
No
No
A
No
No
B
Yes
Yes
AB
Yes
Yes
O
No
Yes
A
Yes
Yes
B
No
No
AB
Yes
Yes
O
No
Yes
A
No
Yes Yes
B
No
AB
No
No
O
No
Yes
Blood Transfus 2015; 13; 347-50 DOI 10.2450/2015.0001-15 © SIMTI Servizi Srl
347 All rights reserved - For personal use only No other uses without permission
Blumberg N et al
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refractoriness is 2-fold higher in patients receiving ABO unselected platelets9 or 5-fold higher when intentionally transfusing ABO antigen incompatible platelets15. Since refractoriness is a very bad prognostic outcome indeed, correlating strongly with mortality, one would think these findings would have resolved the issue, at least in patients with haematological malignancies. That is not the case. There are reviews that suggest that these findings from two randomised trials are not sufficient evidence to support strenuous efforts to transfuse only ABO identical platelets to patients with leukaemia, lymphoma, myelodysplastic syndrome, etc 16. We disagree with that evaluation. Refractoriness is a terrible outcome for these patients, and it is clear from two randomised trials that use of ABO non-identical platelets leads to substantially higher rates of refractoriness. It has been demonstrated that by using inventory management and washing group O platelets as needed, one can provide ABO identical or washed group O platelets (about 5,000 transfusions per year) to almost every patient in a large university hospital17. The exceptions are patients with massive haemorrhage and trauma patients with unknown ABO blood group. After implementation of a strict policy of ABO identical/ washed group O platelets for almost all patients in 2005, the rate of transfusion reactions and red cell alloimmunisation dropped substantially over the ensuing 3 years (by about 35% and 50% respectively). Use of HLA matched platelets also decreased about 50%. Even when universal leucoreduction is implemented, if one stops creating iatrogenic ABO immune complexes, one substantially mitigates immunological events such as fever, rigors, refractoriness and alloimmunisation in platelet transfusion recipients17. Even more important is the question of whether ABO non-identical platelets might actually increase bleeding, due to immunological events interfering with normal haemostasis, such as anti-A binding to recipient endothelial cells, platelets, soluble antigens, etc. There is observational evidence that transfusion of ABO nonidentical platelets in surgical patients increases red cell transfusion needs by about 50% overall18,19. In vitro modelling data demonstrate that ABO antibodies can interfere with platelet aggregation, platelet spreading, thrombin generation, and thromboelastography metrics, all in the direction of impaired haemostatic function20. It may well be that ABO non-identical platelet transfusions cause more harm than good by attenuating existing haemostatic function. Finally, ABO non-identical platelet transfusions may increase mortality in the surgical setting. In an observational study of patients undergoing cardiac surgery, the mortality rate was four-fold higher in patients who received ABO non-identical platelets, even
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transfusions had similar clinical outcomes in terms of engraftment, fever, days in hospital and 90-day survival. However, this analysis was limited to patients who received a total of three platelet transfusions, which may or may not be a sufficient dose to observe any differences in outcomes. Their observations were based upon a subset analysis of 88 patients out of a total cohort of 553. In the entire cohort of 553 patients, the median number of platelet transfusions was two in the 246 patients who received only ABO identical transfusions, one in the 47 patients who received only ABO non-identical transfusions, and four in the 260 patients who received both ABO identical and non-identical platelet transfusions. Thus almost half the patients received only ABO identical platelets. The similar sized group receiving both ABO identical and non-identical platelets is quite different. Those patients received many more platelet transfusions than the group of patients who received only ABO identical transfusions. The authors interpret this, perhaps correctly, as indicating that patients who received both ABO identical and non-identical were sicker patients overall. The other, not mutually exclusive possibility, is that these patients received ABO non-identical platelets, which then contributed to needing more transfusions, and that ABO non-identical platelet transfusions contributed to their morbidity and mortality. Morbidity and mortality were significantly worse in the group receiving ABO non-identical platelets than in the patients receiving fewer numbers of only ABO identical platelet transfusions. There is no easy way to sort out these possibilities from the data. This is particularly true because previous work suggests that the effects of ABO non-identical platelets are cumulative8, and that poor post-transfusion increments only become obvious after three or more ABO non-identical transfusions. Thus patients receiving only one or two ABO non-identical transfusions are unlikely to exhibit any detectable, immediate adverse effects. A randomised trial would be needed to resolve the issue definitively. This is unlikely to be performed. Intentionally transfusing solely ABO non-identical platelets to patients in a clinical trial is not ethical given the risk of haemolysis from administering group O platelets to non-O patients. A randomised trial of current practice vs solely ABO identical platelet transfusions would be ethically sound, but might not fully characterise the effects of repeated, ABO non-identical transfusions. One might, therefore, ask, in the absence of a randomised trial powered for survival outcomes, what do we already know from observational studies or small randomised trials examining clinical outcomes? It has been known for a quarter of a century that for non-leucoreduced platelet transfusions, clinical
Blood Transfus 2015; 13; 347-50 DOI 10.2450/2015.0001-15 348 All rights reserved - For personal use only No other uses without permission
ABO matching of platelet transfusions
That means making every reasonable effort to avoid transfusing ABO incompatible antibody or antigen to patients being given plasma and platelet transfusions. Transfusing incompatible antibody and/or antigen does not make good sense, and this practice will never lead to better outcomes than transfusing ABO identical plasma and platelets. What would make sense? Transfusion services should develop practices that minimise transfusion of ABO incompatible antibody and antigen in platelet transfusions, analogous to the practices we have long since implemented for transfusions of whole blood, red cells, and liquid or fresh-frozen plasma. The Authors declare no conflicts of interest.
References
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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. McManigal S, Sims KL. Intravascular hemolysis secondary to ABO incompatible platelet products - an underrecognized transfusion reaction. Am J Clin Pathol 1999; 111: 202-6. Angiolillo A, Luban NL. Hemolysis following an out-of-group platelet transfusion in an 8-month-old with Langerhans cell histiocytosis. J Pediatr Hematol Oncol 2004; 26: 267-9. Sadani DT, Urbaniak SJ, Bruce M, Tighe JE. Repeat ABOincompatible platelet transfusions leading to haemolytic transfusion reaction. Transfus Med 2006; 16: 375-9. Awad HA, Tantawy AA, El-Farrash RA, et al. CD144+ endothelial microparticles as a marker of endothelial injury in neonatal ABO blood group incompatibility. Blood Transfus 2014; 12: 250-9. Heal JM, Masel D, Blumberg N. Platelets coated with ABO immune complexes from refractory patients are associated with increased adhesion to monocytes. Transfusion 1993; 33 (Suppl): 16S. 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. Heal JM, Rowe JM, Blumberg N. ABO and platelet transfusion revisited. Ann Hematol 1993; 66: 309-14. Heal JM, Rowe JM, McMican A, et al. The role of ABO matching in platelet transfusion. Eur J Haematol 1993; 50: 110-7. Heal JM, Masel D, Blumberg N. Interaction of platelet Fc and complement receptors with circulating immune complexes involving the AB0 system. Vox Sang 1996; 71: 205-11. Goerge T, Ho-Tin-Noe B, Carbo C, et al. Inflammation induces hemorrhage in thrombocytopenia. Blood 2008; 111: 4958-64. Nishimura M, Ishikawa Y, Satake M. Activation of polymorphonuclear neutrophils by immune complex: possible involvement in development of transfusion-related acute lung injury. Transfus Med 2004; 14: 359-67. Laborde EA, Vanzulli S, Beigier-Bompadre M, et al. Immune complexes inhibit differentiation, maturation, and function of human monocyte-derived dendritic cells. J Immunol 2007; 179: 673-81. Solves P, Carpio N, Balaguer A et al. Transfusion of ABO non-identical platelets does not influence the clinical outcome of patients undergoing autologous haematopoietic stem cell transplantation. Blood Transfus 2015; 13: 411-6. Carr R, Hutton JL, Jenkins JA, et al. Transfusion of ABOmismatched platelets leads to early platelet refractoriness. Br J Haematol 1990; 75: 408-13.
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when they received only two platelet transfusions18. That magnitude of difference is unlikely to be explained solely by confounding. When a hospital switched to a policy of transfusing only ABO identical or washed O platelets to surgical patients, in so far as possible, the mortality rate per unit of red cells transfused (a good metric for predicting clinical outcomes) dropped by 28% (from 15.2 deaths to 11.0 deaths per 1,000 red cell transfusions; p=0.013)19. Before-and-after studies are not as robust as randomised trials, but trials of ABO non-identical vs identical platelet transfusions are unlikely to be conducted in surgical patients. Other cohort or epidemiological studies demonstrate that administration of ABO "compatible" but not identical (i.e., group AB) fresh-frozen plasma (in similar amounts to those occurring in platelet transfusions)21,22 or ABO incompatible plasma in platelets23 is associated with statistically significant increases in morbidity (lung injury and sepsis22, or liver injury23) and mortality21,24,25. This is additional evidence that transfusing soluble ABO antigen to recipients with antibody to that antigen leads to the formation of immune complexes that may cause harm. What about studies that appear to show no effect of ABO mismatched platelets? In one, patients who received a first platelet transfusion that was ABO identical were grouped in the ABO identical group, even if the second or later transfusion was ABO non-identical26. This is a scientifically indefensible grouping of patients. It is analogous to patients receiving a little bit of a toxic drug being compared with patients receiving a somewhat larger dose of a toxic drug. When the data from this seemingly discordant second study were further analysed according to the grouping in the original report (patients receiving solely ABO identical platelet transfusions vs patients receiving at least one ABO non-identical transfusion), the patients receiving only ABO identical platelets had better clinical outcomes27. Not a perfect comparison, but the best that can be done scientifically in the absence of a randomised trial. Since it is unlikely that a definitive randomised trial will be performed, it is time to devise practices based upon what we know, and have consistent practices regarding transfusion of ABO incompatible antibody and antigen. ABO antibodies binding to ABO antigens on platelets and soluble proteins interfere with haemostasis and clot formation in vitro20. Transfusions of ABO non-identical platelets and plasma are associated with increased organ injury22,23, red cell transfusion needs18,19, haemolysis2-4, transfusion reactions17, alloimmunisation17, platelet refractoriness8,9,15 and mortality18,19,24,25,28 in randomised trials and observational studies. It seems clear that our clinical practices should reflect what makes most sense.
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7) 8) 9) 10) 11) 12)
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Blood Transfus 2015; 13; 347-50 DOI 10.2450/2015.0001-15 349 All rights reserved - For personal use only No other uses without permission
Blumberg N et al
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24) Benjamin RJ, Antin JH. ABO-incompatible bone marrow transplantation: the transfusion of incompatible plasma may exacerbate regimen-related toxicity. Transfusion 1999; 39: 1273-4. 25) Benjamin RJ, McGurk S, Ralston MS, et al. ABO incompatibility as an adverse risk factor for survival after allogeneic bone marrow transplantation. Transfusion 1999; 39: 179-87. 26) Lin Y, Callum JL, Coovadia AS, Murphy PM. Transfusion of ABO-nonidentical platelets is not associated with adverse clinical outcomes in cardiovascular surgery patients. Transfusion 2002; 42: 166-72. 27) Blumberg N, Heal JM. ABO-mismatched platelet transfusions and clinical outcomes after cardiac surgery. Transfusion 2002; 42: 1527-8; author reply 1528-9. 28) Heal JM, Kenmotsu N, Rowe JM, Blumberg N. A possible survival advantage in adults with acute leukemia receiving ABO-identical platelet transfusions. Am J Hematol 1994; 45: 189-90.
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Correspondence: Neil Blumberg University of Rochester Medical Center Pathology and Laboratory Medicine Transfusion Medicine Unit 601 Elmwood Avenue - Box 608 Rochester, NY 14642, USA e-mail: [email protected]
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16) Shehata N, Tinmouth A, Naglie G, et al. ABO-identical versus nonidentical platelet transfusion: a systematic review. Transfusion 2009; 49: 2442-53. 17) Henrichs KF, Howk N, Masel DS, et al. Providing ABOidentical platelets and cryoprecipitate to (almost) all patients: approach, logistics, and associated decreases in transfusion reaction and red blood cell alloimmunization incidence. Transfusion 2012; 52: 635-40. 18) 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. 19) Refaai MA, Fialkow LB, Heal JM, et al. An association of ABO non-identical platelet and cryoprecipitate transfusions with altered red cell transfusion needs in surgical patients. Vox Sang 2011; 101: 55-60. 20) Refaai MA, Carter J, Henrichs KF, et al. Alterations of platelet function and clot formation kinetics after in vitro exposure to anti-A and -B. Transfusion 2013; 53: 382-93. 21) Shanwell A, Andersson TML, Rostgaard K, et al. Posttransfusion mortality among recipients of ABO-compatible but non-identical plasma. Vox Sang 2009; 96: 316-23. 22) Inaba K, Branco BC, Rhee P, et al. Impact of ABO-identical vs ABO-compatible nonidentical plasma transfusion in trauma patients. Arch Surg 2010; 145: 899-906. 23) Lapierre V, Mahe C, Auperin A, et al. Platelet transfusion containing ABO-incompatible plasma and hepatic venoocclusive disease after hematopoietic transplantation in young children. Transplantation 2005; 80: 314-9.
Blood Transfus 2015; 13; 347-50 DOI 10.2450/2015.0001-15 350 All rights reserved - For personal use only No other uses without permission
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plasma? We treat plasma differently when it is in platelet transfusions than when it is in whole blood or fresh-frozen plasma. Somewhere along the way, as a specialty, we never fully considered the bewildering paradox of such diametrically opposed clinical practices. Which approach makes sense? If we can in good conscience transfuse litres of ABO incompatible plasma with platelets, should we not do the same for fresh-frozen plasma and whole blood? If not, why are we zealously avoiding transfusing litres of incompatible plasma and plasma in whole blood, but entirely comfortable doing so with platelets? In this issue of Blood Transfusion, Pilar Solves and colleagues report on the clinical outcome of recipients of autologous stem cell transplants who received, largely due to chance and availability, either ABO identical, ABO non-identical or both of these types of platelet transfusions14. They found that patients who received solely ABO identical or solely ABO non-identical
©
SI
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er v
The subject of ABO matching of platelet transfusions is one that generates widely varying opinions among transfusion medicine specialists1. That might seem odd, given that our knowledge of the ABO blood group has had 115 years to accumulate. But here is the reality. Transfusion Medicine services transfuse small amounts of ABO incompatible plasma (perhaps 20-40 mL in most cases) with red cells (i.e., so-called universal donor group O). But we never, ever, if we can help it, transfuse group O plasma or whole blood to patients other than O recipients, due to the 200-300 mL of incompatible plasma present. On the other hand, it is entirely acceptable practice in many centres to transfuse 200-300 mL of incompatible group O plasma to non-O recipients when platelets are transfused. Sometimes platelets are transfused daily, for weeks on end, in patients who have undergone ablative chemotherapy for leukaemia or stem cell transplantation. Does this disparity make sense from a scientific or clinical standpoint? Transfusion of ABO incompatible plasma in platelet concentrates causes varying degrees of haemolysis in the recipient, typically resulting in a positive direct antiglobulin test, or, on very rare occasions, haemolysis so severe that it is fatal2-4. Transfused or transplacental ABO incompatible antibody can also bind to and injure endothelial cells5. Transfusion of ABO incompatible, platelet-surface and plasma-soluble ABO antigen in platelet concentrates leads to formation of high molecular weight immune complexes in the recipient6,7. The consequences are not fully known, but include, at minimum, increased rates of platelet destruction and transfusion refractoriness (see Table I)8-10. Immune complexes could, speculatively, lead to inflammation and thrombocytopenia with bleeding 11, neutrophil activation12, organ injury, and immune modulation13 of the transfusion recipient. Commonly employed platelet transfusion practices allowing multiple, ABO plasma incompatible transfusions may be convenient for transfusion services. This approach may also be rationally justifiable on the basis of logistics or availability. Nonetheless, why hasn't our specialty started making scientific and clinical sense when it comes to two incompatible (pun intended) practices involving transfusion of incompatible
Table I - Haemolysis and immune complex formation in platelet transfusion recipients according to donor and recipient ABO blood groups. Platelet donor ABO group
O
A
B
AB
Platelet recipient ABO group
Potential for haemolysis
Potential for circulating immune complexes
A
Yes
Yes
B
Yes
Yes
AB
Yes
Yes
O
No
No
A
No
No
B
Yes
Yes
AB
Yes
Yes
O
No
Yes
A
Yes
Yes
B
No
No
AB
Yes
Yes
O
No
Yes
A
No
Yes Yes
B
No
AB
No
No
O
No
Yes
Blood Transfus 2015; 13; 347-50 DOI 10.2450/2015.0001-15 © SIMTI Servizi Srl
347 All rights reserved - For personal use only No other uses without permission
Blumberg N et al
iz i
Sr l
refractoriness is 2-fold higher in patients receiving ABO unselected platelets9 or 5-fold higher when intentionally transfusing ABO antigen incompatible platelets15. Since refractoriness is a very bad prognostic outcome indeed, correlating strongly with mortality, one would think these findings would have resolved the issue, at least in patients with haematological malignancies. That is not the case. There are reviews that suggest that these findings from two randomised trials are not sufficient evidence to support strenuous efforts to transfuse only ABO identical platelets to patients with leukaemia, lymphoma, myelodysplastic syndrome, etc 16. We disagree with that evaluation. Refractoriness is a terrible outcome for these patients, and it is clear from two randomised trials that use of ABO non-identical platelets leads to substantially higher rates of refractoriness. It has been demonstrated that by using inventory management and washing group O platelets as needed, one can provide ABO identical or washed group O platelets (about 5,000 transfusions per year) to almost every patient in a large university hospital17. The exceptions are patients with massive haemorrhage and trauma patients with unknown ABO blood group. After implementation of a strict policy of ABO identical/ washed group O platelets for almost all patients in 2005, the rate of transfusion reactions and red cell alloimmunisation dropped substantially over the ensuing 3 years (by about 35% and 50% respectively). Use of HLA matched platelets also decreased about 50%. Even when universal leucoreduction is implemented, if one stops creating iatrogenic ABO immune complexes, one substantially mitigates immunological events such as fever, rigors, refractoriness and alloimmunisation in platelet transfusion recipients17. Even more important is the question of whether ABO non-identical platelets might actually increase bleeding, due to immunological events interfering with normal haemostasis, such as anti-A binding to recipient endothelial cells, platelets, soluble antigens, etc. There is observational evidence that transfusion of ABO nonidentical platelets in surgical patients increases red cell transfusion needs by about 50% overall18,19. In vitro modelling data demonstrate that ABO antibodies can interfere with platelet aggregation, platelet spreading, thrombin generation, and thromboelastography metrics, all in the direction of impaired haemostatic function20. It may well be that ABO non-identical platelet transfusions cause more harm than good by attenuating existing haemostatic function. Finally, ABO non-identical platelet transfusions may increase mortality in the surgical setting. In an observational study of patients undergoing cardiac surgery, the mortality rate was four-fold higher in patients who received ABO non-identical platelets, even
©
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transfusions had similar clinical outcomes in terms of engraftment, fever, days in hospital and 90-day survival. However, this analysis was limited to patients who received a total of three platelet transfusions, which may or may not be a sufficient dose to observe any differences in outcomes. Their observations were based upon a subset analysis of 88 patients out of a total cohort of 553. In the entire cohort of 553 patients, the median number of platelet transfusions was two in the 246 patients who received only ABO identical transfusions, one in the 47 patients who received only ABO non-identical transfusions, and four in the 260 patients who received both ABO identical and non-identical platelet transfusions. Thus almost half the patients received only ABO identical platelets. The similar sized group receiving both ABO identical and non-identical platelets is quite different. Those patients received many more platelet transfusions than the group of patients who received only ABO identical transfusions. The authors interpret this, perhaps correctly, as indicating that patients who received both ABO identical and non-identical were sicker patients overall. The other, not mutually exclusive possibility, is that these patients received ABO non-identical platelets, which then contributed to needing more transfusions, and that ABO non-identical platelet transfusions contributed to their morbidity and mortality. Morbidity and mortality were significantly worse in the group receiving ABO non-identical platelets than in the patients receiving fewer numbers of only ABO identical platelet transfusions. There is no easy way to sort out these possibilities from the data. This is particularly true because previous work suggests that the effects of ABO non-identical platelets are cumulative8, and that poor post-transfusion increments only become obvious after three or more ABO non-identical transfusions. Thus patients receiving only one or two ABO non-identical transfusions are unlikely to exhibit any detectable, immediate adverse effects. A randomised trial would be needed to resolve the issue definitively. This is unlikely to be performed. Intentionally transfusing solely ABO non-identical platelets to patients in a clinical trial is not ethical given the risk of haemolysis from administering group O platelets to non-O patients. A randomised trial of current practice vs solely ABO identical platelet transfusions would be ethically sound, but might not fully characterise the effects of repeated, ABO non-identical transfusions. One might, therefore, ask, in the absence of a randomised trial powered for survival outcomes, what do we already know from observational studies or small randomised trials examining clinical outcomes? It has been known for a quarter of a century that for non-leucoreduced platelet transfusions, clinical
Blood Transfus 2015; 13; 347-50 DOI 10.2450/2015.0001-15 348 All rights reserved - For personal use only No other uses without permission
ABO matching of platelet transfusions
That means making every reasonable effort to avoid transfusing ABO incompatible antibody or antigen to patients being given plasma and platelet transfusions. Transfusing incompatible antibody and/or antigen does not make good sense, and this practice will never lead to better outcomes than transfusing ABO identical plasma and platelets. What would make sense? Transfusion services should develop practices that minimise transfusion of ABO incompatible antibody and antigen in platelet transfusions, analogous to the practices we have long since implemented for transfusions of whole blood, red cells, and liquid or fresh-frozen plasma. The Authors declare no conflicts of interest.
References
3)
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2)
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. McManigal S, Sims KL. Intravascular hemolysis secondary to ABO incompatible platelet products - an underrecognized transfusion reaction. Am J Clin Pathol 1999; 111: 202-6. Angiolillo A, Luban NL. Hemolysis following an out-of-group platelet transfusion in an 8-month-old with Langerhans cell histiocytosis. J Pediatr Hematol Oncol 2004; 26: 267-9. Sadani DT, Urbaniak SJ, Bruce M, Tighe JE. Repeat ABOincompatible platelet transfusions leading to haemolytic transfusion reaction. Transfus Med 2006; 16: 375-9. Awad HA, Tantawy AA, El-Farrash RA, et al. CD144+ endothelial microparticles as a marker of endothelial injury in neonatal ABO blood group incompatibility. Blood Transfus 2014; 12: 250-9. Heal JM, Masel D, Blumberg N. Platelets coated with ABO immune complexes from refractory patients are associated with increased adhesion to monocytes. Transfusion 1993; 33 (Suppl): 16S. 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. Heal JM, Rowe JM, Blumberg N. ABO and platelet transfusion revisited. Ann Hematol 1993; 66: 309-14. Heal JM, Rowe JM, McMican A, et al. The role of ABO matching in platelet transfusion. Eur J Haematol 1993; 50: 110-7. Heal JM, Masel D, Blumberg N. Interaction of platelet Fc and complement receptors with circulating immune complexes involving the AB0 system. Vox Sang 1996; 71: 205-11. Goerge T, Ho-Tin-Noe B, Carbo C, et al. Inflammation induces hemorrhage in thrombocytopenia. Blood 2008; 111: 4958-64. Nishimura M, Ishikawa Y, Satake M. Activation of polymorphonuclear neutrophils by immune complex: possible involvement in development of transfusion-related acute lung injury. Transfus Med 2004; 14: 359-67. Laborde EA, Vanzulli S, Beigier-Bompadre M, et al. Immune complexes inhibit differentiation, maturation, and function of human monocyte-derived dendritic cells. J Immunol 2007; 179: 673-81. Solves P, Carpio N, Balaguer A et al. Transfusion of ABO non-identical platelets does not influence the clinical outcome of patients undergoing autologous haematopoietic stem cell transplantation. Blood Transfus 2015; 13: 411-6. Carr R, Hutton JL, Jenkins JA, et al. Transfusion of ABOmismatched platelets leads to early platelet refractoriness. Br J Haematol 1990; 75: 408-13.
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when they received only two platelet transfusions18. That magnitude of difference is unlikely to be explained solely by confounding. When a hospital switched to a policy of transfusing only ABO identical or washed O platelets to surgical patients, in so far as possible, the mortality rate per unit of red cells transfused (a good metric for predicting clinical outcomes) dropped by 28% (from 15.2 deaths to 11.0 deaths per 1,000 red cell transfusions; p=0.013)19. Before-and-after studies are not as robust as randomised trials, but trials of ABO non-identical vs identical platelet transfusions are unlikely to be conducted in surgical patients. Other cohort or epidemiological studies demonstrate that administration of ABO "compatible" but not identical (i.e., group AB) fresh-frozen plasma (in similar amounts to those occurring in platelet transfusions)21,22 or ABO incompatible plasma in platelets23 is associated with statistically significant increases in morbidity (lung injury and sepsis22, or liver injury23) and mortality21,24,25. This is additional evidence that transfusing soluble ABO antigen to recipients with antibody to that antigen leads to the formation of immune complexes that may cause harm. What about studies that appear to show no effect of ABO mismatched platelets? In one, patients who received a first platelet transfusion that was ABO identical were grouped in the ABO identical group, even if the second or later transfusion was ABO non-identical26. This is a scientifically indefensible grouping of patients. It is analogous to patients receiving a little bit of a toxic drug being compared with patients receiving a somewhat larger dose of a toxic drug. When the data from this seemingly discordant second study were further analysed according to the grouping in the original report (patients receiving solely ABO identical platelet transfusions vs patients receiving at least one ABO non-identical transfusion), the patients receiving only ABO identical platelets had better clinical outcomes27. Not a perfect comparison, but the best that can be done scientifically in the absence of a randomised trial. Since it is unlikely that a definitive randomised trial will be performed, it is time to devise practices based upon what we know, and have consistent practices regarding transfusion of ABO incompatible antibody and antigen. ABO antibodies binding to ABO antigens on platelets and soluble proteins interfere with haemostasis and clot formation in vitro20. Transfusions of ABO non-identical platelets and plasma are associated with increased organ injury22,23, red cell transfusion needs18,19, haemolysis2-4, transfusion reactions17, alloimmunisation17, platelet refractoriness8,9,15 and mortality18,19,24,25,28 in randomised trials and observational studies. It seems clear that our clinical practices should reflect what makes most sense.
4)
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5)
6)
7) 8) 9) 10) 11) 12)
13)
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15)
Blood Transfus 2015; 13; 347-50 DOI 10.2450/2015.0001-15 349 All rights reserved - For personal use only No other uses without permission
Blumberg N et al
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24) Benjamin RJ, Antin JH. ABO-incompatible bone marrow transplantation: the transfusion of incompatible plasma may exacerbate regimen-related toxicity. Transfusion 1999; 39: 1273-4. 25) Benjamin RJ, McGurk S, Ralston MS, et al. ABO incompatibility as an adverse risk factor for survival after allogeneic bone marrow transplantation. Transfusion 1999; 39: 179-87. 26) Lin Y, Callum JL, Coovadia AS, Murphy PM. Transfusion of ABO-nonidentical platelets is not associated with adverse clinical outcomes in cardiovascular surgery patients. Transfusion 2002; 42: 166-72. 27) Blumberg N, Heal JM. ABO-mismatched platelet transfusions and clinical outcomes after cardiac surgery. Transfusion 2002; 42: 1527-8; author reply 1528-9. 28) Heal JM, Kenmotsu N, Rowe JM, Blumberg N. A possible survival advantage in adults with acute leukemia receiving ABO-identical platelet transfusions. Am J Hematol 1994; 45: 189-90.
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Correspondence: Neil Blumberg University of Rochester Medical Center Pathology and Laboratory Medicine Transfusion Medicine Unit 601 Elmwood Avenue - Box 608 Rochester, NY 14642, USA e-mail: [email protected]
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16) Shehata N, Tinmouth A, Naglie G, et al. ABO-identical versus nonidentical platelet transfusion: a systematic review. Transfusion 2009; 49: 2442-53. 17) Henrichs KF, Howk N, Masel DS, et al. Providing ABOidentical platelets and cryoprecipitate to (almost) all patients: approach, logistics, and associated decreases in transfusion reaction and red blood cell alloimmunization incidence. Transfusion 2012; 52: 635-40. 18) 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. 19) Refaai MA, Fialkow LB, Heal JM, et al. An association of ABO non-identical platelet and cryoprecipitate transfusions with altered red cell transfusion needs in surgical patients. Vox Sang 2011; 101: 55-60. 20) Refaai MA, Carter J, Henrichs KF, et al. Alterations of platelet function and clot formation kinetics after in vitro exposure to anti-A and -B. Transfusion 2013; 53: 382-93. 21) Shanwell A, Andersson TML, Rostgaard K, et al. Posttransfusion mortality among recipients of ABO-compatible but non-identical plasma. Vox Sang 2009; 96: 316-23. 22) Inaba K, Branco BC, Rhee P, et al. Impact of ABO-identical vs ABO-compatible nonidentical plasma transfusion in trauma patients. Arch Surg 2010; 145: 899-906. 23) Lapierre V, Mahe C, Auperin A, et al. Platelet transfusion containing ABO-incompatible plasma and hepatic venoocclusive disease after hematopoietic transplantation in young children. Transplantation 2005; 80: 314-9.
Blood Transfus 2015; 13; 347-50 DOI 10.2450/2015.0001-15 350 All rights reserved - For personal use only No other uses without permission
