Department of Medicine (Cardiology), Tokai University School of Medicine, Metabolic Disease Research Center, Tokai University Graduate School of Medicine, Isehara, Japan.
Department of Cardiology, Keio University School of Medicine, Tokyo, Japan.
Thromb Res. 2019 Jul;179:121-127. doi: 10.1016/j.thromres.2019.05.007. Epub 2019 May 10.
Thrombin inhibitor and anti-Xa are now widely used in clinical practice. However, the difference between thrombin inhibitor and anti-Xa in prevention of thrombosis is still to be elucidated.
Computer simulator implementing the function of platelet, coagulation, fibrinolysis and blood flow was developed. The function of thrombin is defined as to activated platelet at the rate of 0.01 s and to produce fibrin at the rate of 0.1 s in control. The effect of thrombin inhibitor was settled to reduce the rate of platelet activation and fibrin generation changed from 10 to 100% as compared to the control. The local thrombin generation rate on activated platelet was settled as 1.0 s as a control. The effect of anti-Xa was settled to reduce to thrombin generation rate on activated platelet from 10% to 100% as compared to the control. The sizes of thrombi formed at site of endothelial injury in the presence and absence of thrombin inhibitor and anti-Xa were compared.
The size of thrombi formed by 30-s perfusion of blood at site of endothelial injury reduced both in the presence of thrombin inhibitor and anti-Xa. There was significant positive relationship between thrombin inhibitor effect and the size of formed thrombi with R value of 0.96. (p < 0.0001) However, the sizes of thrombi were not influence by anti-Xa until it decreased 30% or less as compared to control. There was no significant relationship between anti-Xa effect and the size of formed thrombi. (R = 0.39, p = 0.09) Our results suggest the different dose-dependent effects of thrombin inhibitor and anti-Xa on thrombus formation at least in specific conditions. Computer simulation may help to predict quantitative antithrombotic effects of various antithrombotic agents.
凝血酶抑制剂和抗 Xa 因子如今已广泛应用于临床实践中。然而，凝血酶抑制剂和抗 Xa 因子在预防血栓形成方面的差异仍有待阐明。
我们开发了一种计算机模拟器，其可模拟血小板、凝血、纤溶和血流的功能。凝血酶的功能被定义为以 0.01s 的速度激活血小板，并以 0.1s 的速度产生纤维蛋白，作为对照。凝血酶抑制剂的作用被设定为将血小板的激活速度降低 10%至 100%，与对照相比，纤维蛋白的生成速度也降低了 10%至 100%。作为对照，在激活的血小板上局部凝血酶的生成速率设定为 1.0s。抗 Xa 的作用被设定为将激活血小板上的凝血酶生成速率降低 10%至 100%，与对照相比。比较了在存在和不存在凝血酶抑制剂和抗 Xa 因子的情况下，内皮损伤部位形成的血栓的大小。
在存在凝血酶抑制剂和抗 Xa 因子的情况下，内皮损伤部位的血液 30 秒灌注形成的血栓大小均减小。凝血酶抑制剂的作用与形成的血栓大小之间存在显著的正相关关系，R 值为 0.96（p<0.0001）。然而，只有当抗 Xa 因子的作用降低到对照的 30%或以下时，血栓的大小才会受到影响。抗 Xa 因子的作用与形成的血栓大小之间没有显著的关系（R=0.39，p=0.09）。我们的结果表明，在特定条件下，凝血酶抑制剂和抗 Xa 因子对血栓形成的影响存在不同的剂量依赖性。计算机模拟可能有助于预测各种抗血栓药物的定量抗血栓作用。
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