A new look at an old warning: Transfusing <scp>ABO</scp> group‐specific red blood cells after large‐volume low‐titer group <scp>O</scp> whole blood in trauma resuscitation

What's old is new again. Low-titer group O whole blood (LTOWB) is experiencing a modern renaissance for resuscitating trauma patients. However, the question about the serological safety of transfusing ABO group-specific red blood cells (RBC) to non-group O recipients following large-volume LTOWB transfusions persists. The term “persists” indicates that this question had been raised before. In fact, two papers1, 2 from the Korean War era described the transfusions and outcomes of wounded soldiers and concluded thus, “When a man has been given a large amount of universal donor blood, it is recommended that he continue to receive universal donor blood should he need subsequent transfusions during a period of two weeks.”1 This recommendation was given for two reasons: (1) the poor quality of human-derived typing sera used to type locally collected blood had led to several deaths from ABO-incompatible transfusions in theater, and (2) the fear that anti-A/-B from the LTOWB could hemolyze ABO group-specific transfused RBCs. The first problem has been eliminated with modern monoclonal typing sera. The remaining question raised is- does the evidence presented at the time or that has since accumulated for the second concern justify following this recommendation? In these two almost identical papers,1, 2 a group AB patient who suffered an abdominal gunshot wound was singled out for special attention. The authors performed Ashby differential agglutination to determine whether the number of autologous RBCs was diminished at nine time points after receipt of 14 units of LTOWB (titer either <200 or <256) during his surgery. The test was performed by collecting a specific volume of a group A, B, or AB patient's blood, groups A and B RBCs were separated from the transfused group O RBCs by causing the former RBCs to agglutinate using reagent anti-A and -B. The number of remaining unagglutinated RBCs was then manually counted. These remaining unagglutinated cells were group O and were of donor origin. The percentage of donor group O RBCs was calculated by dividing the number of unagglutinated group O RBCs by the total number of RBCs (i.e., autologous and donor RBCs) in the patient's sample. For approximately two weeks following the LTOWB transfusions, this patient's proportion of group O RBCs was ≥64%, with a peak at 92%. These authors interpreted the results of these Ashby tests as evidence that the passively acquired antibodies from the LTOWB transfusion were hemolyzing the patient's autologous RBCs, which led them to suggest not transfusing ABO-specific RBCs following large-volume LTOWB transfusion. However, what makes these observations questionable is their association with very high RBC counts of 6.64 to 8.55 ×106/μL, which are equivalent to hematocrits of 60% and 77%, respectively. These are levels associated with extreme RBC hyperviscosity. Whole blood normally has a hematocrit of 35%–40% and patients who are transfused solely with whole blood typically have hematocrits at or below this fraction. Thus, the reported results are not consistent with current clinical practice. The authors of these two papers also pointed out that “the mild hemolytic phenomenon was not apparent clinically…(his) clinical course throughout this entire period was one of continual improvement,”1 which would probably not be consistent with the occurrence of clinically significant hemolysis. At best a crude estimate of the dynamics of autologous and transfused RBCs, Ashby differential agglutination is no longer performed clinically, and clinical recommendations based on its findings need to be considered with an eye to the possibility of error. Lastly, the authors acknowledge that in their case series of patients, hemolytic reactions following the transfusion of ABO group-specific RBCs to recipients of large-volume LTOWB transfusions did not occur.1 Yet, presumably to support their recommendation of not transfusing ABO group-specific RBCs for two weeks following LTOWB transfusion, they offer what they describe as “circumstantial” evidence of such a hemolytic reaction that was not included in their case series1: A group B patient received “17 pints of group O blood” during his surgery for blast injuries. His blood pressure was unstable several hours after his operation and he was transfused with six “pints of fresh group B blood” (suggesting that they had been collected locally).1 He then became more unstable with hemoglobinuria noted, and he died shortly thereafter.1 While this patient probably hemolyzed, the authors noted that in two of four other cases of hemoglobinuria following the transfusion of “locally procured” ABO group-specific transfusions “…there apparently was a mistake in typing or cross matching.”1 Thus, this patient's apparent hemolysis could have been caused by the mis-transfusion of ABO-incompatible “fresh” RBCs rather than by passively acquired anti-B from the group O blood. In the modern era, the serological safety of transfusing ABO group-specific RBCs following large-volume LTOWB has yet to be established. Most of the contemporary studies have analyzed outcomes following the transfusion of relatively small volumes of incompatible plasma. However, given the absence of contemporary reports about hemolysis in this setting and this fresh look at the historical experience with LTOWB transfusion in military trauma, there does not seem to be a compelling reason to withhold ABO group-specific RBCs following large-volume LTOWB transfusion. A better understanding of large-volume transfusion and the ensuing serological outcomes should continue to be studied. PCS consults for Cerus, is on the scientific advisory board for Haima and Octapharma, and is a co-founder and chief medical officer for Kalocyte. MHY is on the scientific advisory board for Hemanext, consults for Legacy Innovations, has given paid lectures for Terumo BCT and Grifols, and owns equity in Velico Medical, Inc. JRH consults for Hemerus, LLC. APC is the chief scientific officer for Velico Medical, Inc.