PIA2 polymorphism of beta(3) integrins is associated with enhanced thrombin generation and impaired antithrombotic action of aspirin at the site of microvascular injury

Article

关键词: PLATELET GLYCOPROTEIN IIIA;    PL(A2) POLYMORPHISM;    BLEEDING-TIME;    WHOLE-BLOOD;    PLA1/A2 POLYMORPHISM;    CORONARY-THROMBOSIS;    ACTIVATION;    COAGULATION;    ALLOANTIGENS;    PROTHROMBIN;   

DOI  :  10.1161/hc4701.099787

来源: SCIE

【 摘 要 】

Background-Mechanisms by which the PIA2 (Leu33Pro) polymorphism of beta (3) integrins could lead to an increased risk for coronary events are unclear. This study was designed to examine the effect of this polymorphism on blood coagulation. Methods iind Results-In normal subjects (12 with PIA1A1, 9 With PIA1A2, and 3 with PIA2A2), we evaluated the activation of prothrombin, factor V, and factor XIII and fibrinogen removal by quantitative immunoblotting, thrombin-antithrombin III complex generation using ELISA; and levels of fibrinopeptide A and B by high-performance liquid chromatography in blood collected every 30 seconds at sites of standardized microvascular injury before and after 7 days of aspirin ingestion (75 mg/d). Compared with the PIA1A1 subjects, the PIA2 carriers exhibited higher maximum rates of thrombin B-chain generation (by 31.6%; P=0.005), thrombin-antithrombin III complex generation (by 30.7%, P=0.003), fibrinogen consumption (by 31.3%: P=0.002), prothrombin consumption (by 26.1%, P=0.011), and activation of factor V (by 14.1%,; P=0.033) and factor XIII (by 27.0%; P=0.012). In the PIA1A1 homozygotes, aspirin ingestion resulted in reductions in the velocity of thrombin B-chain formation (by 32.1%;, P=0.007), prothrombin consumption (by 30.4%; P=0.018), factor Va generation (by 28.9%; P=0.014), fibrinogen removal (by 41.2%; P=0.001), and factor XIII activation (by 22.6%; P=0.026). In the PIA2 carriers, aspirin did not alter the velocity of all these processes. After aspirin ingestion, fibrinopeptide A and B concentrations in the last 30-second interval were significantly reduced, but only in the PIA1A1 subjects. Conclusions-The presence of the pI(A2) allele is associated with enhanced thrombin formation and an impaired antithrombotic action of aspirin, which might favor coronary thrombosis in the PIA2 carriers.

【 授权许可】

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