Genotyping for platelet‐specific antigens: techniques for the detection of single nucleotide polymorphisms

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Abstract
Accurate typing of patients for platelet‐specific (human platelet) antigens (HPA) is required in several different clinical situations, and blood services need to maintain panels of HPA‐typed apheresis platelet donors and whole‐blood donors to support HPA alloimmunized patients. Six clinically relevant HPA alloantigen systems have been described and, in addition, a significant number of HPA alloantigens with a highly skewed allele frequency or of very low immunogenicity have been reported. Certain well‐characterized biallelic systems such as Gov have not as yet been included in the HPA nomenclature but are included in this review. Biochemical studies have identified the platelet membrane proteins on which the HPA antigens are localized. Cloning of the genes encoding these proteins and the realization that there is adequate mRNA in fresh platelets has led to identification of the molecular basis of HPA antigens over the last decade. All but one of the biallelic platelet‐specific alloantigen systems are based on a single nucleotide polymorphism in the DNA sequence, corresponding to a single amino acid substitution in the encoded primary protein sequence. The discovery of the genetic basis of the alloantigens has allowed the development of polymerase chain reaction‐based techniques for HPA genotyping using genomic DNA. The genetic basis of the HPA alloantigens, the most commonly used genome typing techniques and their pitfalls, and future developments, are discussed in this review.