The effect of extended c, E and K matching in females under 45 years of age on the incidence of transfusion-induced red blood cell alloimmunisation

Maternal alloantibodies directed against fetal red blood cell (RBC) antigens may cause potentially life-threatening haemolytic disease of the fetus and newborn (HDFN). Dutch transfusion guidelines therefore prescribe preventive cEK matching for all (pre-)fertile females. To quantify the impact of cEK matching, we compared overall and antigen-specific cumulative RBC alloimmunisation incidences in females and males aged <45 years. Among a multicentre cohort comprised of patients who received their first and subsequent RBC unit between 2005 and 2019, first-formed RBC alloantibodies were detected in 47 of 2998 (1 center dot 6%) females and 49 of 2507 (2 center dot 0%) males. Comparing females and males, overall alloimmunisation incidences were comparable (3 center dot 1% [95% confidence interval (CI) 2 center dot 1-4 center dot 4] versus 3 center dot 5% (95% CI 2 center dot 4-4 center dot 9, P = 0 center dot 853) after 10 units transfused). However, cEK alloimmunisation incidences were significantly lower among females (0 center dot 6% (95% CI 0 center dot 3-1.5) versus 2 center dot 2% (95% CI 1 center dot 5-3 center dot 4, P = 0 center dot 001) after 10 units transfused). Yet, despite cEK-matching guidelines being in effect, 6 center dot 5%, 3 center dot 6% and 0 center dot 2% of all RBC units remained mismatched for c, E or K antigens respectively. Most of these mismatches were almost always due to emergency settings. Even though cEK alloimmunisation was not prevented completely, implementation of cEK matching resulted in an alloantigen-exposure risk reduction of up to 98%.