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 (1·6%) females and 49 of 2507 (2·0%) males. Comparing females and males, overall alloimmunisation incidences were comparable (3·1% [95% confidence interval (CI) 2·1–4·4] versus 3·5% (95% CI 2·4–4·9, P = 0·853) after 10 units transfused). However, cEK alloimmunisation incidences were significantly lower among females (0·6% (95% CI 0·3–1.5) versus 2·2% (95% CI 1·5–3·4, P = 0·001) after 10 units transfused). Yet, despite cEK‐matching guidelines being in effect, 6·5%, 3·6% and 0·2% 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%.