Disequilibrium of Human Platelet Antigen 1 (HPA-1) in U.S. Population

Abstract Background: Alloimmunization against Human Platelet Antigens (HPA) is associated with Neonatal Alloimmune Thrombocytopenia (NAIT), post-transfusion purpura and refractoriness for platelet transfusion. A flexible BeadChip™ design was developed to simultaneously detect 22 platelet antigens, including HPA-1, and used to assay over 1,000 random blood donors from across the United States. Methods: Samples from 19 labs/centers from across the country were assayed for 11 HPA loci (HPA-1 through 9, 11 and 15) using the BioArray Solutions HPA Assay. Each locus was independently assessed for Hardy-Weinberg Equilibrium. Results: Allele and genotype frequencies for each locus were reported. Platelet antigens HPA-2 through HPA-9, HPA-11 and HPA-15 were all found to be in Hardy-Weinberg Equilibrium with a Chi-Squared value of <3.84 (1 degree of freedom, 5% confidence interval). HPA-1, however, did not exhibit Hardy-Weinberg Equilibrium yielding a Chi-Squared value of 43.4. Conclusions: After reaffirming there was no sampling preference by inclusion of a second blinded random group, it was acknowledged that HPA-1 did not conform to a Mendelian distribution of alleles. The lower incidence of heterozygote HPA-1 individuals may lend credence to the recent finding by Ivanov et al (Akush Ginekol, 2007) linking the polymorphism in GPIIIa that is responsible for the HPA-1 antigen with embryo implantation failure. Further research may help elucidate the causes behind the HPA-1 disequilibrium and how much implantation failure impacts HPA-1 frequencies.