In a viewpoint article published in Lancet Haematology, the authors discuss the available data and hypotheses that potentially account for the association of sickle cell disease (SCD) with high rates of alloimmunization following transfusion therapy in both high-income and low-income countries, particularly in sub-Saharan Africa, and propose ways to improve prevention of alloimmunization in both settings.

“Sickle cell disease is the most frequent inherited disorder in sub-Saharan Africa and in many high-income countries,” the authors explained in their report. “People with sickle cell disease have the highest rate of alloimmunization of all patients undergoing blood transfusion.”

The authors highlighted that alloimmunization against red blood cell antigens and post-transfusion hemolysis, which can be life-threatening in severe cases, in SCD results primarily from blood group differences between donors and recipients.

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In high-income countries, alloimmunization can be primarily attributed to blood group disparity between blood donors, who are predominantly of European descent, and recipients, who are mostly of African descent.

The authors proposed that a solution would be to encourage populations of African descent in high-income countries to donate blood to reduce the disparities in blood group antigen frequencies between donors and patients. They also suggest that matching in high-income countries can be extended from ABO, RhD, C, c, E, e, and K to include Fya, Fyb, Jka, Jkb, S, and s for patients with alloantibodies.

Although the disparities in blood group antigen frequencies between donors and patients are already lower in sub-Saharan Africa, the rates of alloimmunization are also high. The authors attributed this to matching strategies that are limited to ABO blood group and RhD. They suggest that matching strategies in low-income countries should be upgraded to take into account the most immunogenic blood group antigens, including for ABO, RhD, C, c, E, e, and K.

Additional suggestions for how to improve rates of alloimmunization are related to consideration of the inflammatory status of the patient and the characteristics of the red blood cell products.

“[Low-income countries and high-income countries] must learn from each other to ensure benefit to patients through the implementation of transfusion strategies preventing alloimmunization while remaining mindful of the benefit-cost ratio and resource availability in [low-income countries],” the authors concluded.


Pirenne F, Floch A, Diop S. Alloimmunisation against red blood cells in sickle cell disease: transfusion challenges in high-income and low-income countries. Lancet Haematol. Published online April 12, 2023. doi:10.1016/S2352-3026(23)00066-2