Polyphosphate accelerates factor V activation by factor XIa
Polyphosphate accelerates factor V activation by factor XIa
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DOI：
10.1160/th14-06-0515
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发表时间：
2015-03-01
影响因子：
6.7
通讯作者：
Morrissey, James H.
中科院分区：
文献类型：
--
作者：
Choi, Sharon H.;Smith, Stephanie A.;Morrissey, James H.
因子Va将因子Xa激活凝血酶原的速率提高4至5个数量级。从其前体因子V产生起始水平的因子Va是止血早期的关键事件，因为因子V表现出可忽略的辅因子活性。虽然凝血酶是因子V的最有效的生理学反向激活剂，但第一凝血酶原酶复合物在凝血酶产生之前需要因子Va的来源。Whelihan等人的最近研究（J Thromb Haemost 2010; 8：1532-1539）将因子XIa鉴定为因子V的初始凝血酶非依赖性活化的候选物，尽管该反应缓慢并且需要相对高浓度的因子V和XIa。活化的血小板分泌聚磷酸盐，我们以前已经证明它是有效的促凝血剂。我们现在报告，多磷酸盐大大加速因子Ⅴ激活因子XIa，这是支持的聚磷酸盐聚合物的大小分泌的活化的人血小板。这一发现提供了额外的证据表明因子XIa介导的因子Va的产生可能有助于止血的启动。
Factor Va enhances the rate of prothrombin activation by factor Xa by four to five orders of magnitude. Production of initiating levels of factor Va from its precursor, factor V, is a critical event early in haemostasis, as factor V exhibits negligible cofactor activity. While thrombin is the most potent physiological back-activator of factor V, the first prothrombinase complexes require a source of factor Va prior to thrombin generation. A recent study by Whelihan et al. (J Thromb Haemost 2010; 8:1532-1539) identified factor XIa as a candidate for the initial thrombin-independent activation of factor V, although this reaction was slow and required relatively high concentrations of factors V and XIa. Activated platelets secrete polyphosphate, which we previously showed to be potently procoagulant. We now report that polyphosphate greatly accelerates factor V activation by factor XIa, and that this is supported by polyphosphate polymers of the size secreted by activated human platelets. This finding provides additional evidence that factor XIa-mediated generation of factor Va may contribute to the initiation of haemostasis.