Hemolytic disease of the fetus and newborn in the sensitizing pregnancy where anti‐D was incorrectly identified as RhIG

BACKGROUND: Hemolytic disease of the fetus and newborn (HDFN) is a potentially fatal complication in Rh‐incompatible pregnancies and rarely occurs in the sensitizing pregnancy. Distinguishing RhIG from true anti‐D identified is challenging. A case of severe HDFN in which a sample drawn at 28 weeks showed anti‐D antibody (3+ strength) attributed to RhIG is described. RBC antibody testing early in pregnancy was negative. At birth, the infant was severely anemic and maternal anti‐D titer was 1:256. This case represents a clinically significant anti‐D in the sensitizing pregnancy that was missed due to confusion with RhIG. METHODS: To determine if agglutination strength could be helpful, a retrospective chart‐review using both electronic and paper medical records was performed on 348 samples identified as RhIG and 52 true anti‐D samples. The agglutination strength of antibody was recorded for each sample. RESULTS: For RhIG, there was an even distribution between the weak to moderate agglutination strength (w+, 1+, and 2+) results (35%, 26%, and 33%, respectively) and just 6% had a 3+ strength. Agglutination strength in patients with high titer (≥1:16) anti‐D showed they often (44.4%) have 1+ or 2+ agglutination reactivity. CONCLUSIONS: These results show that agglutination strength alone does not provide reliable evidence to distinguish RhIG from high titer anti‐D antibodies. We recommend that in cases where there is any uncertainty about whether the anti‐D reactivity is due to RhIG, titers should be performed to rule out clinically significant anti‐D antibody.