Is Female Sex a Risk Factor for Red Blood Cell Alloimmunization After Transfusion? A Systematic Review

Large scale red blood cell (RBC) antigen genotyping of donors is currently well developed. There is scarce information, however, to select patients who might benefit from preemptive extended RBC antigen-matched transfusions. Female sex has been proposed as a risk factor for RBC alloimmunization after transfusion. To asses whether females respond differently to RBC alloantigens compared with males, we conducted a literature review on RBC alloimmunization. Clinical studies on RBC alloimmunization incidence were searched for in databases from 1950 through 2011. Studies were included when data were available to calculate the female-to-male risk ratio for alloimmunization. Based on the reported age, adult patients (>18 years) were distinguished from pediatric patients (≤18 years), and articles were analyzed according to disease categories. Thirty articles fulfilled the inclusion criteria. The Mantel-Haenszel risk ratio estimate of combined adult studies showed that women with sickle cell disease had an increased relative risk (27%) on RBC alloantibodies compared with men. Other groups showed equal alloimmunization risk in women and men. Women slightly more often than men possess RBC antibodies. This is likely explained by more exposure to immunizing events through pregnancy and/or transfusions in females with sickle cell disease. The results support the current policy implemented in many countries for Rhesus/Kell matching in patients with a hemoglobinopathy irrespective of sex. Thus, based solely on sex difference, the results do not justify recommending additional matching for women, besides preemptive K and c antigen matching for women during the (pre-) fertile age, as already applied in many European countries for the prevention of fetal morbidity.