Red blood cell alloimmunization and antigen matching in sickle cell disease – the African perspective

Abstract

In sickle cell disease (SCD), blood transfusion facilitates improved blood and tissue oxygenation, reduces the propensity to sickling by diluting host cells, and suppresses the production of red blood cells (RBCs) containing sickle haemoglobin (HbS). Delivery of RBC transfusions to patients with SCD varies by method (simple vs. exchange) and frequency (episodic vs. chronic). However, due to the genetic differences between blood donors and recipients, repeated transfusions increase the risk of developing alloantibodies to RBC antigens. The antigens most frequently involved belong to the Rh, Kell, Kidd, Duffy, Lewis, and MNS blood group systems. Consequences of RBC alloimmunization include delays and difficulties in obtaining compatible blood for future transfusions, the occurrence of delayed haemolytic transfusion reactions (DHTRs), the hyperhaemolysis syndrome and autoimmunization. In Europe and USA, RBC alloimmunization rates ranging from 18% to 76% have been reported in SCD while other multiply transfused (OMT) patients had alloimmunization rates of 5% to 20% indicating that SCD patients are at a higher risk of developing RBC alloantibodies. To prevent alloimmunization in SCD patients, the standard practice in Europe and USA is to determine their extended RBC phenotype (ABO, Rh, Kell, Kidd, Duffy, Lewis, MNS) before commencing transfusion therapy and perform antigen matching for C, E and K antigens for patients without prior alloantibody formation. However in Africa, lower RBC alloimmunization prevalence rates of 6–10% have been reported in SCD patients and no differences were observed between SCD and OMT patients. This may be explained by the presumed high phenotypic compatibility between donors and SCD patients who were all Black Africans. Also, a low transfusion load (a median 3 U of blood were transfused) in SCD patients might have led to the poor response to alloantigenic challenge. Anti‐K alloimmunization was notably rare among African SCD patients compared to anti‐S. In many African countries, pre‐transfusion immunohaematologic testing includes neither the detection of RBC alloimmunization nor preventive antigen matching. Most transfusion laboratories are understaffed and underequipped; they perform ABO/D typing plus room temperature saline cross‐matches and do not screen for RBC alloantibodies. Hence, immunized SCD patients are not diagnosed and do not have the opportunity of receiving antigen‐negative blood. Furthermore, data on the occurrence of DHTRs are lacking. Introducing pre‐transfusion RBC alloantibody screening in all African countries will significantly improve the transfusion management of SCD patients. A program of limited phenotype matching for C, E and S antigens is recommended to prevent additional alloantibody formation in immunized SCD patients in Africa.

Red blood cell alloimmunization in sickle cell disease and in thalassaemia: current status, future perspectives and potential role of molecular typing

“…The major goals of RBC transfusions in patients with SSA are to improve the distribution of oxygen to tissue, to reduce the tendency to form sickle cells by diluting host cells and to temporarily suppress the production of red cells containing HbS . The HbS gene is distributed worldwide, occurring mainly in subjects of African descent .…”

Red cell alloimmunization in transfused patients: A silent epidemic revisited

“…[10] The formation of red cell antibodies may be influenced by the patients’ age at which the transfusions are given or when chronic transfusion therapy is started. Four studies on RBC alloimmunization performed in (preterm) neonates who received multiple transfusions during the first 3-4 months of life did not encounter any RBC antibodies.…”

Medical and economic implications of strategies to prevent alloimmunization in sickle cell disease

“…For example, Zheng and coworkers reported that patients with SCD residing in the United States had a higher rate of alloimmunization and more alloantibodies per person compared with other countries, such as Brazil, where the genetic composition of blood donors more closely resembles that of transfusion recipients . The rate of alloimmunization is believed to be less than 10% in sub‐Saharan Africa, where there is significant genetic overlap between donor and recipients …”

“…20 The rate of alloimmunization is believed to be less than 10% in sub-Saharan Africa, where there is significant genetic overlap between donor and recipients. 32, 35,51 Several research groups have investigated whether transfusions undertaken as part of an RBC exchange program are more (or less) likely to result in alloimmunization compared with simple transfusions. [52][53][54] Based on the results from several studies, RBC exchange is associated with a lower risk of alloimmunization per unit transfused compared with simple transfusion, although the pathophysiology underlying this observation is not well understood.…”