The effect of human platelet alloantigen polymorphisms on the in vitro responsiveness to adrenaline and collagen.

A number of clinical studies have suggested that carriage of the low frequency allele (b) of the human platelet antigen 1 (HPA-1) system is a risk factor for coronary thrombosis. We have examined the effect of a series of HPA biallelic polymorphisms (systems -1, -2, -3 and -5) on the in vitro platelet aggregation in response to adrenaline and collagen in 30 healthy volunteers. There was a significantly higher prevalence (10 out of 18) of carriers of the HPA-1b polymorphism among subjects showing a > 50% aggregation response to adrenaline ('responders') than the prevalence (1/12) in 'non-responders' (P < 0.05). Platelets heterozygous for the HPA-1b polymorphism showed a significantly higher rate (slope) and greater extent (%) of adrenaline-induced aggregation than platelets not carrying the HPA-1b allele (P < 0.05). A greater extent of collagen-induced aggregation was also demonstrated in HPA-1ab platelets (P < 0.05). Inhibition of adrenaline-induced aggregation following incubation with aspirin was greater (P < 0.01) in HPA-1ab than in HPA-1aa platelets. Collagen-induced aggregation was slower in carriers of the HPA-5b allele than in HPA-5aa subjects (P < 0.05). Polymorphisms of the HPA-2 and HPA-3 systems were not associated with different aggregation responses to either adrenaline or collagen. These results support the clinical observation that polymorphism HPA-1b may predispose to increased platelet thrombogenicity and suggest that the presence of polymorphism HPA-5b might render the platelet less reactive to collagen.