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(1) Background: ABO blood group incompatibility between the mother and fetus protects against anti-D immunization by pregnancy. The possible role of ABO incompatibility in protecting against anti-human platelet antigen-1a immunization is unclear. (2) Methods: This study retrospectively screened 817 families (mother-father-neonate trios) of suspected fetal and neonatal alloimmune thrombocytopenia for inclusion. ABO genotypes were determined in 118 mother-child pairs with confirmed alloimmune thrombocytopenia due to anti-HPA-1a antibodies, and 522 mother-child pairs served as the control group. The expression of blood group antigen A on platelets was determined in 199 consecutive newborns by flow cytometry and compared with adult controls. (3) Results: ABO incompatibility between mother and fetus did not protect against anti-human platelet antigen-1a immunization by pregnancy. ABO blood groups of mothers and/or fetuses were not associated with the severity of fetal and neonatal alloimmune thrombocytopenia. The expression pattern of blood group A antigens on the platelets of newborns mirrored that of adults, albeit on a lower level. Blood group A antigen was detected on a subpopulation of neonatal platelets, and some newborns revealed high platelet expression of A determinants on all platelets (type II high-expressers). (4) Conclusion: The lack of a protective effect of ABO incompatibility between mother and fetus against anti-human platelet antigen-1a immunization by pregnancy may indicate that fetal platelets are not the cellular source by which the mother is immunized. [ABSTRACT FROM AUTHOR]

BACKGROUND Fetal human platelet antigen (HPA) genotyping is required to determine whether the fetus is at risk and whether prenatal interventions to prevent fetal bleeding are required in pregnant women with a history of fetal and neonatal alloimmune thrombocytopenia (FNAIT). Methods for noninvasive genotyping of HPA alleles with the use of maternal plasma cell-free DNA were published recently but do lack internal controls to exclude false-negative results. STUDY DESIGN AND METHODS Cell-free DNA was isolated from plasma of four pregnant women with a history of FNAIT caused by anti-HPA-1a and controls. A primer panel was designed to target sequences flanking single-nucleotide polymorphisms (SNPs)/exonic regions of ITGB3 (HPA-1), ITGA2B (HPA-3), ITGA2 (HPA-5), CD109 (HPA-15), RHD, RHCE, KEL, DARC, SLC14A1, GYPA, GYPB, and SRY. These regions and eight anonymous SNPs were massively parallel sequenced by semiconductor technology. RESULTS The mean (±SD) number of reads for targeted SNPs was 5255 (±2838). Fetal DNA was detected at a median of 4.5 (range, 2-8) polymorphic loci. The mean fractional fetal DNA concentration in cell-free maternal plasma was 8.36% (range, 4.79%-15.9%). For HPA-1, nonmaternal ITGB3 sequences (c.176T, HPA-1a) were detected in all HPA-1ab fetuses. One HPA-1bb fetus was unequivocally identified, showing the pregnancy was not at risk of FNAIT. CONCLUSION We have successfully established massively parallel sequencing as a novel reliable method for noninvasive genotyping of fetal HPA-1a alleles. This technique may also allow the safe detection of other fetal blood group polymorphisms frequently involved in FNAIT and hemolytic disease of the newborn. [ABSTRACT FROM AUTHOR]