Early occurrence of red blood cell alloimmunization in patients with sickle cell disease

Abstract

Red blood cell (RBC) alloimmunization is a major complication of transfusion therapy in sickle cell disease (SCD). Identification of high-risk patients is hampered by lack of studies that take the cumulative transfusion exposure into account. In this retrospective cohort study among previously non-transfused SCD patients in the Netherlands, we aimed to elucidate the association between the cumulative transfusion exposure, first alloimmunization and independent risk factors. A total of 245 patients received 11 952 RBC units. Alloimmunization occurred in 43 patients (18%), half of them formed their first alloantibody before the 8th unit. In patients with exposure to non-extended matched transfusions (ABO and RhD) the cumulative alloimmunization risk increased up to 35% after 60 transfused units. This was significantly higher compared to a general transfused population (HR 6.6, CI 4.2-10.6). Receiving the first transfusion after the age of 5 was an independent risk factor for alloimmunization (HR 2.3, CI 1.0-5.1). Incidental, episodic transfusions in comparison to chronic scheme transfusions (HR 2.3, CI 0.9-6.0), and exposure to non-extended matched units in comparison to extended matching (HR 2.0, CI 0.9-4.6) seemed to confer a higher alloimmunization risk. The majority of first alloantibodies are formed after minor transfusion exposure, substantiating suggestions of a responder phenotype in SCD and stressing the need for risk factor identification. In this study, older age at first transfusion, episodic transfusions and non-extended matched transfusions appeared to be risk factors for alloimmunization.

Genotyping in Sickle Cell Disease Patients: The French Strategy

“…There is evidence to suggest that individuals may be high or low ‘responders', depending on their propensity to produce antibodies [11,12], but the responder status of a patient cannot be predicted until a positive result is obtained in an antibody screening test. Delayed hemolytic transfusion reactions (DHTRs) are a major concern in SCD patient care, and are generally associated with the production of antibodies [13,14].…”

Identification of genetic biomarkers for alloimmunization in sickle cell disease

“…In addition, finding compatible units for alloimmunized patients can be challenging and time-consuming and may therefore lead to life threatening situation for acutely ill patients (Yazdanbakhsh et al, 2012). Compared to the general population, the rate of alloimmunization in SCD is exceptionally high with a frequency of approximately 30% and reports ranging from 18% to 76% with ABO and Rhesus (Rh) D antigen matching only (Chou et al, 2012;Sins et al, 2016). The antigenic differences between recipients of primarily African descent and donors with generally a Caucasian background is an influential factor herein (Vichinsky et al, 1990).…”

“…Compared to the general population, the rate of alloimmunization in SCD is exceptionally high with a frequency of approximately 30% and reports ranging from 18% to 76% with ABO and Rhesus (Rh) D antigen matching only (Chou et al , ; Sins et al , ). The antigenic differences between recipients of primarily African descent and donors with generally a Caucasian background is an influential factor herein (Vichinsky et al , ).…”

Towards a Regional Registry of Extended Typed Blood Donors: Molecular Typing for Blood Group, Platelet and Granulocyte Antigens

“…The concept of extended matching in transfusion therapy of such patients is appropriate to prevent alloimmunization events [28,29,30]. Especially, patients who were already immunized by past transfusion could benefit from extensive antigen matching beyond C/c, E/e, and K [31,32]. As recently reported in a large cohort of transfused patients, the most immunogenic antigens were in order K, E, C W , e, Jk a , c, and Fy a [33].…”