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

Abstract

Summary 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%.

The Development and Consequences of Red Blood Cell Alloimmunization

“…They differ significantly in form and function, in density, and in overall distribution, and these differences likely influence how sentinel immune factors engage these antigens and the overall consequence of alloantibody binding should an incompatible transfusion occur. The implementation of improved genotyping methods and databases that allow hospital transfusion services to more adequately match alloantigens prior to transfusion and be aware of historical alloantibodies that may have evanesced will be important when seeking to prevent alloimmunization and/or alloantigen reexposure in previously sensitized patients ( 155 – 158 ). Attempts to prevent Hb- and heme-induced immune activation are underway, as are studies seeking to define the utility of complement inhibition in preventing and treating DHTRs and associated hyperhemolysis ( 61 , 62 , 159 , 160 ).…”

How do we perform intrauterine transfusions?

“…This approach resulted in an alloimmunization rate of only 0.3% in females compared to 1.4% in males during the same period. 55 Although matching for additional antigens requires extra labor, time, and cost, it may be beneficial in preventing further maternal alloimmunization and HDFN. On the other hand, the utility of antigen matching has been questioned since prior pregnancy is a major source of exposure to non-self RBC antigens.…”

“…The Netherlands, with its efficient large‐scale national blood supply, implemented extended antigen matching not only for IUT, but also matching for c‐, E‐, K‐antigens in all females under age 45 years. This approach resulted in an alloimmunization rate of only 0.3% in females compared to 1.4% in males during the same period 55 . Although matching for additional antigens requires extra labor, time, and cost, it may be beneficial in preventing further maternal alloimmunization and HDFN.…”

Transfusion‐induced red blood cell alloimmunisation is unhampered in elderly patients

“…Analyses were restricted to males due to preventative Rh/K matching in (pre)-fertile females. 8 First, via Kaplan-Meier analyses we compared RBC alloimmunisation incidences among different age groups (i.e. <25, 25-45, 45-65, >65 years).…”