Increased resistance to tissue plasminogen activator-induced fibrinolysis in healthy subjects from Thailand

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Abstract

There is significant variability in blood coagulation among world populations. In particular, there may exist important differences in regulation of the fibrinolytic system in Asian populations that contribute to diseases of thrombosis and hemostasis. To investigate this issue, we compared fibrinogen concentration, plasma clot formation, and fibrinolytic resistance of healthy Asian subjects from Hat Yai, Songkhla, Thailand (Thai) vs. healthy North American subjects from Seattle, Washington, USA (SEA). Citrated plasma samples were obtained from healthy adult volunteers. Fibrinogen concentration was measured in plasma by the method of Clauss to examine for baseline differences of fibrinogen concentration. Samples were then standardized to 2.8 mg/ml fibrinogen using physiological buffer for each sample prior to fibrinolytic testing using rotational thromboelastometry (ROTEM) to examine for differences of clot lysis not attributable to fibrinogen concentration alone. Clot lysis was examined with ROTEM extrinsic pathway activation in the presence of 0, 0.5, and 1.0 μg/ml of tissue plasminogen activator (tPA). Two-way repeated measures analysis of variance was used to determine the effects of tPA and study group on ROTEM parameters. N = 49 Thai samples were compared with N = 58 SEA samples. Mean (SD) fibrinogen concentration was significantly increased for the Thai group at 4.03 (0.79) mg/ml vs. the SEA group at 3.66 (0.70) mg/ml (t test P = 0.014). After standardization of all samples to equivalent fibrinogen concentration, there were no differences in clot formation between groups without tPA. There was a significant effect of increasing tPA concentration on all ROTEM parameters except for clotting time. There were significant individual differences for amplitude at 10 min and lysis onset time, where amplitude at 10 min was significantly increased and lysis onset time was significantly prolonged for Thai vs. SEA at tPA concentrations of 0.5 and 1.0 μg/ml. Variability in thrombosis and hemostasis in Asians vs. other populations is likely to involve differences of fibrinogen concentration and regulation of clot lysis.

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