Vetnuus | August 2024 11 Leading Article Although no hemolysis was observed, microscopic to macroscopic agglutination in all major crossmatches between canine or feline donors and rabbit recipients was present, and canine donors had 1.4 times the risk of macroscopic agglutination than feline donors. These results suggest that rabbits have naturally occurring alloantibodies against both canine and feline RBC alloantigens and support this study’s second hypothesis that feline RBCs may have better serological compatibility than canine RBCs. Possible explanations for this potential difference include the density and immunogenicity of species-specific RBC alloantigens (eg, DEA-1) and the specificity and cross-reactivity of naturally occurring rabbit alloantibodies. In terms of comparative hematology, rabbit RBCs exhibit a typical mammalian, anucleated, biconcave disc morphology similar to canine and feline RBCs.11 However, rabbits have higher RBC turnover and a predicted random destruction rate of 0.5% per day, resulting in an average life span of 45–70 days.11 Rabbit RBC life span is thus more similar to feline RBCs (66–72 days) and approximately half that of canine RBCs (110–120 days). Despite rabbit hemostasis being similar, generally, to other mammals, rabbit blood hemolyzes easily and clots quickly, which may complicate phlebotomy for crossmatches and blood donation.11 While there are >300 breeds of domestic rabbits, all are descendants of a single species, the European rabbit (Oryctolagus cuniculus), originally native to the Iberian Peninsula.11 Although there are no widely clinically recognized blood types in rabbits, it is possible potential rabbit RBC alloantigens and naturally occurring alloantibodies exist in varying prevalence among different domestic rabbit breeds and geographically distinct populations similar to domestic dogs. A single colony of laboratory rabbits was shown to develop varying titers of alloantibodies after repeated allogeneic blood transfusions, suggesting recipient sensitization occurs in rabbits similar to other mammals.12 Further investigations performing crossmatches between rabbit recipients and donors of different rabbit breeds could improve our understanding of rabbit blood types and allogeneic transfusions. The main disadvantages of xeno-transfusion across species includes documented decreased donor RBC survival, putative increased risk of transfusion reactions, and recipient sensitization. In experimental studies in domestic cats, the average transfused RBC survival was <4 days with canine xenotransfusions, whereas the average transfused RBC survival reached 30–38 days with autotransfusions or compatible allogeneic blood transfusions.13,14 A recent multicenter, prospective, observational study found that canine xeno-transfusion to feline patients resulted in no acute adverse reactions other than self-limiting, febrile, nonhemolytic transfusion reactions.15 However, 25 of 39 (64%) feline patients developed delayed hemolytic transfusion reactions within 1–6 days after xenotransfusion.15 Subsequent canine xenotransfusion to cats >6 days after initial transfusion has led to severe anaphylactic reactions and death.16,17 In cockatiels (Nymphicus hollandicus) transfused with whole blood from blue-fronted Amazon parrots (Amazona aestiva) and pigeons (Columba livia), xeno-transfusion resulted in a shorter survival of transfused RBCs (<3 days), whereas no difference was found in RBC survival between autotransfusions and allogeneic blood transfusions (10–17 days).18 Similarly, in sun conure (Aratinga solstitialis) transfused with whole blood from white-eyed conures (Psittacara leucophthalmus), transfused RBCs had decreased survival (4.5 days) compared with RBC survival after autotransfusions and allogeneic blood transfusions (8.5–10 days).19 In the limited number of case reports of xeno-transfusion in nondomestic species, no acute or delayed transfusion reactions were observed.2–4 To the authors’ knowledge, there are no case reports of serial xenotransfusions and subsequent recipient sensitization in rabbits. Further prospective research is needed to determine if xenotransfusion is associated with a higher incidence of acute and delayed transfusion reactions in rabbits than allogeneic transfusions. Given the higher RBC turnover observed in rabbits coupled with decreased RBC survival shown in other species receiving xenotransfusions, an emergency xeno-transfusion may only potentially aid a rabbit recipient for a short duration. These findings build on a similar recent observational study that evaluated the major and minor crossmatch compatibility between DEA-1-positive and DEA1-negative RBCs and rabbit recipients.9 Similar to the results of the current study, Cutler et al found all major crossmatches between canine donors and rabbit recipients resulted in macroscopic agglutination; however, the macroscopic agglutination observed was more variable and severe (1+ to 4+).9 This variability could be due to differences in rabbit populations, blood sample and donor collection, or subtle differences in tube crossmatch methodology. While crossmatch incompatibility is predictive of acute transfusion reactions in some studies, the degree of incompatibility (eg, agglutination grade) is not predictive of life-threatening acute transfusion reactions.5,20 Cutler et al found that all minor crossmatches between canine donors and rabbit recipients resulted in hemolysis, suggestive of naturally occurring canine alloantibodies against rabbit RBCs.9 No minor crossmatches were performed in this study given the difficulty of extracting a reliable volume of donor plasma from pigtails.Currently, there is insufficient evidence for, or against, minor crossmatching in canine and feline transfusion medicine.21 The minor crossmatch has almost universally been discontinued in human pretransfusion testing due to enhanced human blood donor screening and the increasing use of blood component therapy versus whole blood transfusions.22 While there are multiple internationally recognized canine blood groups categorized under the DEA system, DEA-1 is considered the most clinically significant in canine transfusion medicine. Although titers of naturally occurring anti-DEA-1 alloantibodies have not been identified, sensitization of DEA-1-negative dogs with DEA-1positive RBCs can lead to acute hemolytic transfusion reactions.23 In feline transfusion medicine, the AB blood group system is most commonly used in clinical practice, with type A cats having low titers of naturally occurring anti-B alloantibodies, whereas type B cats have high titers of naturally occurring anti-A alloantibodies.5,7 Similar to a previous study,9 the current study found no significant difference in agglutination between DEA-1-positive and DEA1-negative crossmatched to rabbit recipient blood. The current study additionally found no significant difference between feline type A and type B blood donors. These data suggest that rabbits may have naturally occurring alloantibodies against canine and feline RBC alloantigens other than or in addition to DEA-1, type A, or type B. The significant difference in agglutination between canine and feline donors suggests that rabbits’ alloantibodies may target, or bind with variable affinity, different RBC alloantigens between the 2 species. While the biochemical and genetic basis for the feline AB blood group system has been characterized, the DEA system has not been characterized to the same degree, and other RBC alloantigens have been recently found (eg, Dal, Kai 1, Kai 2).8 In a recent multicenter, prospective, observational study, no significant difference in crossmatch incompatibility or transfusion reactions was found between feline patients receiving canine xenotransfusions with DEA-1-positive or DEA-1-negative blood.15 >>> 12
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