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

Abstract

Summary. 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 collageninduced 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. Collageninduced 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.

A functional genomics approach reveals novel quantitative trait loci associated with platelet signaling pathways

“…There is conflicting evidence in the literature of the association of rs5918 with the platelet response. [14][15][16][17]29,30 This could be due to the sample size of earlier studies, which, in sharp contrast with this study, have generally been too small to ascertain small effects of a SNP with a MAF of 0.15 (MAF in this study was 0.186, because of enrichment of HPA-1b1b individuals in the PFC).…”

“…To date, most investigations of such QTLs have focused on platelet surface receptors; particularly those responsible for fibrinogen-mediated platelet aggregation via the integrin ␣IIb␤3, [14][15][16][17][18] or adhesion to collagen via ␣2␤1, 19,20 or von Willebrand factor via GPIb␣, [21][22][23][24] or the platelet signaling receptors for most of the physiologic agonists. [2][3][4]10,25,26 The robustness of the observed genetic associations has been limited for many studies by small cohort sizes and, with a few exceptions, by inadequate selection of single nucleotide polymorphisms (tagSNPs) to ascertain underlying sequence variation.…”

Enhanced platelet adhesion in essential thrombocythemia after in vitro activation

“…The appearance of individual variability in the response to adrenaline has been studied in the healthy population, and when including 140 individuals, 16% were classified as non-responders to adrenaline-induced platelet aggregation in plasma [33]. This variability in the adrenaline response in healthy subjects has been confirmed by other investigations also studying platelet function in plasma [20,[34][35][36]. No study has been designed with the purpose of investigating individual variability of adrenaline-response in ET patients.…”

Platelet functional implications of glycoprotein Ibα polymorphisms in African Americans

“…Furthermore, platelet aggregation using PRP was normal in those with and without the Ko a (HPA-2b) polymorphism [7]. In another study, epinephrine and collagen induced platelet aggregation was measured in PRP in 30 young healthy Greek volunteers and found not to be significantly different between those who were carriers of Ko a (HPA-2b) and those who were homozygous for Ko b (HPA-2a) [20]. In yet another study of healthy young adults in Vienna, who were either HPA-2a (Thr,Thr) or HPA-2b (Thr, Met/Met,Met), platelet function testing indicated no significant difference in collagen/ epinephrine closure times, as measured by the PFA-100 TM assay.…”