Red cell transfusion and alloimmunization in sickle cell disease

Abstract

Red cell transfusion remains a critical component of care for acute and chronic complications of sickle cell disease. Randomized clinical trials demonstrated the benefits of transfusion therapy for prevention of primary and secondary strokes and postoperative acute chest syndrome. Transfusion for splenic sequestration, acute chest syndrome, and acute stroke are guided by expert consensus recommendations. Despite overall improvements in blood inventory safety, adverse effects of transfusion are prevalent among patients with sickle cell disease and include alloimmunization, acute and delayed hemolytic transfusion reactions, and iron overload. Judicious use of red cell transfusions, optimization of red cell antigen matching, and the use of erythrocytapheresis and iron chelation can minimize adverse effects. Early recognition and management of hemolytic transfusion reactions can avert poor clinical outcomes. In this review, we discuss transfusion methods, indications, and complications in sickle cell disease with an emphasis on alloimmunization.

Figure 1.

Factors that contribute to alloimmunization in sickle cell disease. The prevalence of alloimmunization in sickle cell disease (SCD) is high compared to that in the general population. One of the key factors behind alloimmunization is recipient-donor mismatch of Rh and K antigens. The majority of Blacks lack C, E, and K antigens. The frequencies of C, E, and K are higher in blood donor populations, leading to increased risk of alloantigen exposure with red cell transfusion. Transfusing red cells matched for Rh and K decreases the rate of alloimmunization; however, RH genetic diversity contributes to a persistent risk of Rh antibody development. Most patients with SCD have one or more RH variants. Common RH alleles in patients with SCD are depicted in panel 2. Red boxes represent RHD exons, and blue boxes represent RHCE exons. The dashed line indicates gene deletion. Vertical lines reflect the positions of amino acid substitutions. Patients with RH variants can form antibodies against the Rh epitopes they lack. SCD is a chronic inflammatory state. Hemolysis leads to elevated levels of circulating hemoglobin and free heme, which activate macrophages and neutrophils, and leads to the secretion of pro-inflammatory cytokines. Patients with high levels of inflammation are at increased risk of alloimmunization. While the immunological pathways contributing to alloimmunization are complex, it is becoming increasingly clear that immune system dysregulation influences antibody formation. IL-1: interleukin -; IL-6: interleukin-6; IFNγ: interferon gamma. Created with Biorender.com.