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Hemolytic transfusion reactions in sickle cell disease: underappreciated and potentially fatal
Ferrata Storti Foundation
Swee Lay Thein,1 France Pirenne,2,3 Ross M. Fasano,4,5 Anoosha Habibi,3,6 Pablo Bartolucci,6 Satheesh Chonat,5 Jeanne E. Hendrickson7
and Sean R. Stowell4
1National Heart, Lung and Blood Institute, National Institutes of Health, Bethesda, MA, USA; 2Etablissement Français du Sang, INSERM U955, Université Paris Est Créteil, Créteil, France; 3Laboratoire d'Excellence GR-Ex, Paris, France; 4Center for Transfusion Medicine and Cellular Therapies, Department of Laboratory Medicine and Pathology, Emory University School of Medicine, Atlanta, GA, USA; 5Aflac Cancer and Blood Disorders Center, Department of Pediatrics, Emory University School of Medicine, Atlanta, GA, USA; 6Sickle Cell Referral Center, Department of Internal Medicine, Henri-Mondor University Hospital– UPEC, AP-HP, Créteil, France and 7Departments of Laboratory Medicine and Pediatrics, Yale University School of Medicine, New Haven, CT, USA
Introduction
Patients with sickle cell disease (SCD) often receive red blood cell (RBC) trans- fusion support for the prevention and management of many acute and chronic disease complications.1-3 The beneficial effects of transfusion therapy observed in recent clinical studies, and the lack of effective treatments for this population of patients, have led to an increased use of blood.4 While RBC transfusions may be life-saving, we are concerned about their expanding use and would like to raise awareness of RBC alloimmunization, a major complication of transfusion, partic- ularly in patients with SCD in whom the incidence is much higher than in other groups of patients.5 Hemolytic transfusion reactions, which primarily occur in RBC alloimmunized patients, are often under-recognized in patients with SCD, in particular because the symptoms mimic those of acute vaso-occlusive crises, and serological markers of new alloantibodies may be equivocal.6,7 In addition to increasing the risk of potentially fatal acute or delayed-type hemolytic transfusion reactions (DHTR),8-10 the development of RBC alloantibodies can also significantly delay the procurement of compatible RBC for future transfusions.11
Currently, there is a lack of evidence in this area to inform best practice, and management is often based on anecdotal case reports. While there have been reports of a variety of cases illustrating the challenges associated with recognizing and treating hemolytic transfusion reactions in patients with SCD,12,13 the poten- tial reasons for the higher incidence of RBC alloantibodies in SCD patients merit discussion. Here, we share our experience in managing alloimmunized patients and hemolytic transfusion reactions, and challenge the medical community to consider lessons learned from diagnostic criteria and mitigation policies for trans- fusion-related acute lung injury (TRALI) in order to minimize the morbidity and mortality associated with transfusion in patients with SCD.
Why are patients with sickle cell disease at high risk of red blood cell alloimmunization?
One possible reason for the relatively high incidence of alloimmunization observed in patients with SCD is the mismatch in RBC antigens expressed in the donor pool (primarily Northern European descent) and patients with SCD (mainly of African descent).8 Mismatch of RBC antigens is not the only reason, however, as a significant proportion of patients with SCD who receive phenotypically matched blood from exclusively ethnically matched donors still become alloimmunized.9 Molecular analyses of the RH genes in patients with SCD and African-American donors reveal remarkable RH allelic diversity in this population, with mismatch between serological Rh phenotype and RHD or RHCE genotype due to variant RH alleles in a large proportion of the individuals.10 Thus, RH genotyping in addition to serological typing may be required to identify the most compatible RBC, though it is not yet known if such an approach completed prospectively instead of reactively (after antibodies against alloantigens in the RH family form) will decrease RBC alloimmunization, and whether it will be possible to source rarer RH genotypes on a regular basis for patients on a transfusion program. The clinical context of RBC transfusion in SCD may also contribute to the higher rate of alloimmunization; the
Haematologica 2020 Volume 105(3):539-544
Correspondence:
SEAN R. STOWELL
srstowe@emory.edu
Received: August 26, 2019. Accepted: December 18, 2019. Pre-published: February 6, 2020.
doi:10.3324/haematol.2019.224709
Check the online version for the most updated information on this article, online supplements, and information on authorship & disclosures: www.haematologica.org/content/105/3/539
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