Recombinant factor VIIa enhances platelet adhesion and activation under flow conditions at normal and reduced platelet count
Recombinant factor VIIa enhances platelet adhesion and activation under flow conditions at normal and reduced platelet count
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DOI：
10.1111/j.1538-7836.2005.01227.x
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发表时间：
2005-04-01
影响因子：
10.4
通讯作者：
De Groott, PG
中科院分区：
文献类型：
--
作者：
Lisman, T;Adelmeijer, J;De Groott, PG
背景资料：重组凝血因子VIIa（rFVIIa）是一种用于治疗血管并发血友病的药物，也适用于治疗其他临床疾病，包括血小板减少症。普遍认为rFVIIa通过增强损伤部位的凝血酶生成发挥作用。然而，这是否以及如何影响血小板粘附和聚集尚不清楚。一种药物：确定在正常和血小板计数降低的流动条件下，rFVIIa诱导的凝血酶生成对血小板粘附和聚集的影响。方法：将洗涤后的血小板与红细胞混合，获得不同血小板数的无血浆血。在不存在或存在由纯化的凝血因子rFVIIa、因子（F）X和凝血酶原组成的凝血酶生成系统的情况下，将重构血液灌注在胶原或纤维蛋白原包被的表面上。结果如下：此外，凝血因子rFVIIa，FX和凝血酶原洗涤血小板和红细胞增强血小板粘附和聚集胶原蛋白和粘附，并蔓延到纤维蛋白原在正常血小板计数和血小板数低至10 000 μ L-1。rFVIIa介导的凝血酶生成增强了血小板的活化状态（通过细胞内钙通量测量），并增强了促凝血磷脂的暴露（通过膜联蛋白A5结合测量）。结论：综上所述，rFVIIa诱导的凝血酶形成增加血小板粘附和聚集可能解释了rFVIIa在血小板减少性疾病和血小板计数正常患者中的治疗作用，即（i）增强原发性止血和（ii）增强促凝血表面，导致纤维蛋白形成增加。
Background: Recombinant factor VIIa (rFVIIa), which was developed for treatment of inhibitor-complicated hemophilia, appears Suitable as prohertiostatic agent in other clinical disorders including patients with thrombocytopenia. It is generally accepted that rFVIIa functions by enhancement of thrombin generation at the site of injury. It is, however, unknown if and how this affects platelet adhesion and aggregation. ONectives: To determine the effect of rFVIIa-inediated thrombin generation on platelet adhesion and aggregation under flow conditions at normal and reduced platelet counts. Methods: Washed platelets and red cells were combined to obtain plasma-free blood with different platelet counts. The reconstituted blood was perfused over a collagen or fibrinogen-coated surface in the absence or presence of a thrombin generating system consisting of purified coagulation factors rFVIIa, factor (F)X and prothrombin. Results: Addition of coagulation factors rFVIIa, FX and prothrombin to washed platelets and red cells enhanced platelet adhesion and aggregation to collagen and adhesion and spreading to fibrinogen at normal platelet count and at platelet numbers as low as 10 000 mu L-1. rFVIIa-mediated thrombin generation enhanced the activation state of platelets as measured by intracellular calcium fluxes, and enhanced the exposure of procoagulant phospholipids as measured by annexin A5 binding. Conchisions: Taken together, increased platelet adhesion and aggregation by rFVIIa-inediated thrombin formation may explain the therapeutic effects of rFVIIa in thrombocytopenic conditions and in patients with a normal platelet count by (i) enhancement of primary hemostasis and (ii) enhancement of procoagulant surface leading to elevated fibrin formation.