Significance of ABO Blood Group Incompatibility between Mother and Child Regarding Incidence and Severity of Fetal and Neonatal Alloimmune Thrombocytopenia

Abstract

In fetal and neonatal alloimmune thrombocytopenia (FNAIT), maternal alloantibodies directed against paternally inherited platelet antigens cause fetal/neonatal platelet degradation and interfere with vascular endothelial cells. This results in intracranial hemorrhage (ICH) in approximately 10% of severely thrombocytopenic neonates. Non-invasive monitoring of the fetal platelet count is not possible and prophylaxis of fetal bleeding during pregnancy itself is not harmless either. For HDFN, the red blood cell counterpart of FNAIT, a protective effect of fetomaternal ABO blood group incompatibility against anti-D-immunization is known. For FNAIT, an association between the ABO blood group of the mother and severity of the disease is hypothesized. ABO genotyping in 165 mother-child pairs with proven FNAIT was performed with in-house TaqMan real time PCR assays to detect the major ABO alleles ABO*A1.01, ABO*A2.01, ABO*B.01, ABO*O.01 and ABO*O.02. The cohorts were stratified according to antibody specificities. Severity of FNAIT was defined through neonatal platelet count nadir, ICH-occurrence, and birth weight. Distribution of ABO phenotypes among immunized women, their neonates and 45295 first time blood donors were not statistically different. Frequency of ABO-incompatible pregnancies was not reduced among immunized mothers, compared to 522 pregnancies with thrombocytopenic neonates without FNAIT. Fetomaternal ABO incompatibility was not associated with FNAIT severity. ICH frequency was significantly higher in neonates with phenotype O than A, most likely due to a type I error. Neonates of A2 mothers had a significantly higher birth weight than neonates of A1 mothers, this finding was only valid without association to any antibody specificity and needs to be replicated in a larger cohort. A protective effect of fetomaternal ABO incompatibility against anti-HPA-1a immunization was not observed. This may indicate that instead of fetal platelets, particles of the syncytiotrophoblast (which lack ABO antigens) are the cellular source by which immunization is triggered already early in the first pregnancy. This should be regarded in the development of FNAIT prophylaxis. No maternal ABO blood group was associated with risk for alloimmunization or more severe FNAIT. Therefore, risk assessment regarding the outcome and necessary therapy intensity does not seem possible based on maternal blood groups.