Alloimmunisation against red blood cells in sickle cell disease: transfusion challenges in high-income and low-income countries

Abstract

Sickle cell disease is the most frequent inherited disorder in sub-Saharan Africa and in many high-income countries (HICs). Transfusion is a key element of treatment, but it results in high rates of alloimmunisation against red blood cell antigens and post-transfusion haemolysis, which can be life-threatening in severe cases. The prevention of alloimmunisation is, therefore, an important issue in both HICs and in low-income countries (LICs). In HICs, the main reason for high alloimmunisation rates is blood group disparity between blood donors, who are mostly of European descent, and the patients, who are mostly of African descent. However, alloimmunisation rates also remain high in sub-Saharan Africa despite the homogeneity of blood group antigen frequencies between donors and patients; this occurrence is probably due to matching strategies limited to ABO blood group and RhD. However, other possible underlying causes of alloimmunisation have also been suggested, with each cause affecting HICs and LICs in different ways-eg, the immunogenetic and inflammatory status of the patient and the characteristics of the red blood cell products. In this Viewpoint, we discuss the available data and hypotheses that potentially account for the association of sickle cell disease with high rates of alloimmunisation in both settings, HICs and LICs (focusing particularly on sub-Saharan Africa), and the challenges faced by HICs and LICs to improve prevention of alloimmunisation.