The Development of Severe Anti-HPA 1a-Related Neonatal Alloimmune Thrombocytopenia Is Influenced by the Maternal ABO Type.

About 100 000 pregnant women were included in a screening and intervention program aimed to reduce morbidity and mortality related to neonatal alloimmune thrombocytopenia (NAIT). NAIT due to HPA 1a immunization have many features in common with hemolytic disease of the newborn (HDN) caused by RhD immunization. Platelets express blood group A and B antigens, and as described in HDN, ABO incompatibility between mother and fetus could possibly protect against immunization against HPA 1a. The aim of the study was to describe the ABO distribution among the immunized mothers and examine whether ABO status of the mother influenced the severity of thrombocytopenia in the newborn. ABO typing of HPA 1a immunized women was routinely performed by serological methods during the screening. ABO genotyping resolving the major alleles (A¹, A², B, O¹, O^1v or O² alleles) of the women and their newborns was performed by PCR-RFLP methods. The ABO distribution among the immunized HPA 1a negative women was found to be similar to the normal distribution in the Norwegian population, which may indicate that the ABO type does not influence the immunization mechanism. However, we find that HPA 1a immunized women of blood group A have a higher risk of delivering a child with severe NAIT (platelet count < 50×10⁹/L) than women with blood group O. Twenty percent of the immunized women with blood group O gave birth to children with severe NAIT, compared to 46% among the immunized blood group A mothers, resulting in a relative risk of 0.43 (95% CI 0.25–0.76). The ABO type of the newborn was not found to influence development of severe NAIT. The O¹/O^1v allele distribution among the immunized women with blood group O resembles the distribution reported for a Swedish population. However, only 2/22 (9.1%) pregnancies among the O^1v negative blood group O mothers resulted in a newborn with severe NAIT, compared to 10/34 (29.4%) among the O^1v-positive blood group O women, resulting in a relative risk of 0.31 (95% CI 0.07–1.28). The observation that the immune response against HPA 1a may have different consequences depending on the ABO blood group of the mother is interesting. O^1v, also termed O02, constitutes a separate but ancient allelic lineage at the ABO locus and we are now in the process of examining if our observation is related to linkage disequilibrium between the ABO gene and one or more pregnancy-related immunoregulatory genes.