Our cell-based model of haemostasis replaces the traditional 'cascade' hypothesis, and proposes that coagulation takes place on different cell surfaces in three overlapping steps: initiation, amplification, and propagation. In highlighting the importance of cellular control during coagulation, the cell-based model allows a more thorough understanding of how haemostasis works in vivo, and sheds light on the pathophysiological mechanisms behind certain coagulation disorders. For instance, this model proposes that haemophilia involves a failure of platelet-surface FXa generation, leading to a lack of platelet-surface thrombin production. Our data suggest that high-dose FVIIa is able to bind weakly to activated platelets, independently of tissue factor, in order to generate sufficient amounts of FXa to support a burst bf thrombin generation in the absence of FIXa/FVIIIa. The considerable success of high-dose recombinant FVIIa (rFVIIa; NovoSeven, Novo Nordisk, Copenhagen, Denmark) as a therapy for patients with haemophilia and inhibitors has led to its use in a growing number of alternative indications. We believe that even in the presence of the FIXa/FVIIIa complex, rFVIIa may be able to enhance both FXa and FIXa levels on the surface of activated platelets, thus increasing the production of thrombin.

中文翻译：

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基于细胞的凝血模型和因子VIIa的作用。

我们基于细胞的止血模型取代了传统的“级联”假说，并提出凝结发生在三个重叠步骤的不同细胞表面：起始，扩增和繁殖。在强调凝血过程中细胞控制的重要性时，基于细胞的模型可以更全面地了解止血在体内的工作原理，并阐明某些凝血障碍背后的病理生理机制。例如，该模型提出血友病会导致血小板表面FXa产生失败，从而导致血小板表面凝血酶产生不足。我们的数据表明，高剂量FVIIa能够与活化的血小板弱结合，而与组织因子无关，为了产生足够量的FXa以支持在不存在FIXa / FVIIIa的情况下爆发bf凝血酶。大剂量重组FVIIa（rFVIIa； NovoSeven，Novo Nordisk，哥本哈根，丹麦）作为血友病和抑制剂患者的疗法取得了相当大的成功，导致其在越来越多的替代适应症中得到应用。我们相信，即使存在FIXa / FVIIIa复合物，rFVIIa仍能够增强活化血小板表面上的FXa和FIXa水平，从而增加凝血酶的产生。