Page 29 - Haematologica March 2020

Hemolytic transfusion reactions in SCD
to reduce heme levels,46 although the level of anemia and inability to transfuse may prevent this from becoming a realistic option in many patients. Intravenous immunoglobulin and corticosteroids may further reduce hemolysis in the setting of DHTR.47 While characteristics of the transfused unit, such as RBC storage, may have an impact on transfusion outcomes in SCD,48 recent studies suggest that exuberant complement activation may account for the most severe DHTR with accompanying hyperhemolysis.49 Consistent with this, treatment of patients experiencing DHTR-associated hyperhemolysis with eculizumab, an anti-C5 complement-blocking anti- body, has been shown to reverse complement activation, reduce hemolysis, and result in rapid clinical improve- ment.49,50 While additional studies are needed, these reports hold promise and suggest that more effective treatment options that could significantly improve patients’ care may be on the horizon (Table 1).
Avoiding additional RBC transfusion at the time of an ongoing DHTR with bystander hemolysis is recommend- ed, as transfusion of even seemingly compatible RBC that are negative for all alloantigens that the patient is known to be alloimmunized against may worsen the ongoing hemolysis. If the alloantibody in question cannot be iden- tified or if it is identified but compatible units cannot be allocated, alloantibody function tests can be ordered to assess the clinical significance of a patient’s alloantibod- ies. This test typically involves evaluation of monocyte engulfment of antibody-coated cells in vitro as a read out of alloantibody function.51 However, this approach is time-consuming, and may not provide timely results in an acute setting.51 Should the clinical status of the patient necessitate consideration of a “least incompatible” RBC transfusion, rituximab prophylaxis has been described to reduce DHTR in small case reports.52,53
Summary
In conclusion, RBC alloantibodies and DHTR are not uncommon in patients with SCD. They are underappreci- ated and, in our opinion, are the single leading cause of transfusion-associated morbidity and mortality in this vul- nerable population of patients. Many of the challenges associated with preventing and treating DTHR can be addressed by developing international and national RBC alloantibody databases, limiting RBC transfusions to situa- tions that are evidence-based, implementing more accurate diagnostic strategies (through routine use of HbA quantifi- cation and standard antibody screening), better under- standing the pathophysiology, and formally testing addi- tional prophylactic and treatment approaches to prevent and treat these reactions. We urge our colleagues in hema- tology, transfusion medicine (from donor centers to trans- fusion services), laboratory information technology, fund- ing agencies, and regulatory agencies to view RBC alloim- munization and DTHR in patients with SCD with a similar urgency as TRALI was viewed in past decades. Such a heightened awareness, and subsequent industry changes, are predicted to directly reduce the significant transfusion- associated complications that contribute to the current morbidity and mortality of patients with SCD.
Acknowledgments
This perspective was initially conceived as a result of a post- conference formal meeting after the first international conference on delayed type transfusion reactions in Creteil, France. We thank all those who organized, supported and attended this con- ference, while particularly acknowledging those who directly participated in the post meeting and subsequent discussions on this topic, including Karina Yazdanbakhsh, Armand Mekontso Dessap, Lubka Roumenina, Eldad Hod and Chris Tormey.
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