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 freque ncy allele (b) of the human platelet antigen 1 (HPA-1) system is a risk fac tor 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 platel et aggregation in response to adrenaline and collagen in 30 healthy volunte ers. There was a significantly higher prevalence (10 out of 18) of carriers of the HPA-1b polymorphism among subjects showing a >50% aggregation respo nse to adrenaline ('responders') than the prevalence (1/12) in 'non-respond ers' (P<0.05). Platelets heterozygous for the HPA-1b polymorphism showed a significantly higher rate (slope) and greater extent (%) of adrenaline-indu ced aggregation than platelets not carrying the HPA-1b allele (P<0.05). A g reater extent of collagen-induced aggregation was also demonstrated in HPA- 1ab platelets (P<0.05). Inhibition of adrenaline-induced aggregation follow ing 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 observati on that polymorphism HPA-1b may predispose to increased platelet thrombogen icity and suggest that the presence of polymorphism HPA-5b might render the platelet less reactive to collagen.