Kjalke M, Monroe D M, Hoffman M, Oliver J A, Ezban M, Roberts H R
Center for Thrombosis and Hemostasis, University of North Carolina at Chapel Hill, USA.
Thromb Haemost. 1998 Oct;80(4):578-84.
Factors VIIa, Xa, and IXa play different roles in the initiation of tissue factor-dependent coagulation. The consequences of competing with the different enzymes were investigated, thereby examining the effects of inhibiting the initiation process at different steps. Active site-inactivated factors VIIa, Xa, and IXa (FVIIai, FXai, and FIXai, respectively) were added to various cell-based assays mimicking the individual steps in tissue factor-initiated coagulation. In an assay involving tissue factor-expressing monocytes, coagulation proteins and unactivated platelets, FVIIai and FXai inhibited platelet activation and thrombin generation while FIXai only inhibited thrombin generation. FVIIai inhibited factor Xa generation and subsequent thrombin generation on monocytes, while FXai inhibited thrombin generation on the monocytes as well as on the activated platelets. FIXai had no effect on factor Xa or thrombin generation on the monocytes, but inhibited factor Xa and subsequent thrombin generation on the activated platelets. FVIIai had no effect on the reactions taking place on the activated platelets. The data confirm a model where tissue factor/factor VIIa mediates factor Xa generation and subsequent prothrombin activation on the tissue factor-bearing cells. Thrombin then activates platelets, which serve as the physiologically important surface for large-scale thrombin generation.
凝血因子VIIa、Xa和IXa在组织因子依赖性凝血的起始过程中发挥着不同作用。研究了与不同酶竞争的后果，从而考察了在不同步骤抑制起始过程的效果。将活性位点失活的凝血因子VIIa、Xa和IXa（分别为FVIIai、FXai和FIXai）添加到各种基于细胞的试验中，这些试验模拟了组织因子启动的凝血过程中的各个步骤。在一项涉及表达组织因子的单核细胞、凝血蛋白和未活化血小板的试验中，FVIIai和FXai抑制血小板活化和凝血酶生成，而FIXai仅抑制凝血酶生成。FVIIai抑制单核细胞上因子Xa的生成及随后的凝血酶生成，而FXai抑制单核细胞以及活化血小板上的凝血酶生成。FIXai对单核细胞上因子Xa或凝血酶的生成没有影响，但抑制活化血小板上因子Xa及随后的凝血酶生成。FVIIai对活化血小板上发生的反应没有影响。这些数据证实了一种模型，即组织因子/凝血因子VIIa介导组织因子表达细胞上因子Xa的生成及随后的凝血酶原激活。然后凝血酶激活血小板，血小板是大规模凝血酶生成的重要生理表面。
