Department of Regulatory Medicine for Thrombosis, Nara Medical University, 840 Shijo-cho, Kashihara, Nara, Japan.
Thromb Haemost. 2013 Aug;110(2):316-22. doi: 10.1160/TH13-02-0159. Epub 2013 May 2.
Coagulation factor VIII (FVIII) plays an essential role in haemostasis. To date, physiologic activity of FVIII circulating in the bloodstream (S-FVIII) is evaluated by classic coagulation assays. However, the functional relevance of FVIII (-von Willebrand factor complex) immobilised on thrombogenic surfaces (I-FVIII) remains unclear. We used an in vitro perfusion chamber system to evaluate the function of I-FVIII in the process of mural thrombus formation under whole blood flow conditions. In perfusion of either control or synthetic haemophilic blood, the intra-thrombus fibrin generation on platelet surfaces significantly increased as a function of I-FVIII, independent of S-FVIII, under high shear rate conditions. This I-FVIII effect was unvarying regardless of anti-FVIII inhibitor levels in synthetic haemophilic blood. Thus, our results illustrate coagulation potentials of immobilised clotting factors, distinct from those in the bloodstream, under physiologic flow conditions and may give a clue for novel therapeutic approaches for haemophilic patients with anti-FVIII inhibitors.
凝血因子 VIII（FVIII）在止血中起着至关重要的作用。迄今为止，通过经典凝血检测来评估在血液中循环的 FVIII 的生理活性（S-FVIII）。然而，固定在血栓形成表面的 FVIII（-von Willebrand 因子复合物）的功能相关性尚不清楚。我们使用体外灌注室系统，在全血流条件下评估在壁血栓形成过程中 I-FVIII 的功能。在控制或合成血友病血液的灌注中，血小板表面的血栓内纤维蛋白生成随着 I-FVIII 的增加而显著增加，这与 S-FVIII 无关，在高剪切率条件下更是如此。在合成血友病血液中无论抗 FVIII 抑制剂的水平如何，这种 I-FVIII 作用都保持不变。因此，我们的结果说明了在生理流动条件下，固定的凝血因子的凝血潜力与在血液中的凝血潜力不同，这可能为有抗 FVIII 抑制剂的血友病患者提供新的治疗方法。
