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.
Theodoropoulos
I
I
First Department of Internal Medicine, Amalia Fleming Hospital, Athens, Greece.
Christopoulos
C
C
Metcalfe
P
P
Dimitriadou
E
E
Economopoulos
P
P
Loucopoulos
D
D
D000328:Adult; D016824:Antigens, Human Platelet / Q000235:genetics*; D001241:Aspirin / Q000494:pharmacology; D001792:Blood Platelets / Q000276:immunology*; D003094:Collagen / Q000494:pharmacology*; D003328:Coronary Thrombosis / Q000276:immunology*; D004837:Epinephrine / Q000494:pharmacology*; D005260:Female; D005838:Genotype; D006801:Humans; D008297:Male; D008875:Middle Aged; D010974:Platelet Aggregation / Q000187:drug effects*; D010975:Platelet Aggregation Inhibitors / Q000494:pharmacology; D011110:Polymorphism, Genetic; D012307:Risk Factors
D016824:Antigens, Human Platelet; D010975:Platelet Aggregation Inhibitors; C083451:human platelet antigen 1b; D003094:Collagen; D001241:Aspirin; D004837:Epinephrine