Polyphosphate as a general procoagulant agent.
Polyphosphate as a general procoagulant agent.
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DOI：
10.1111/j.1538-7836.2008.03104.x
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发表时间：
2008-10
期刊：
影响因子：
--
通讯作者：
Morrissey JH
中科院分区：
文献类型：
--
作者：
Smith SA;Morrissey JH
多磷酸盐由活化的血小板分泌，我们最近发现它主要通过触发接触途径和促进因子V活化来加速血液凝固。我们现在报告，多磷酸盐显着缩短了血友病A和B患者血浆的凝血时间，其促凝作用是添加到重组因子VIIa。多磷酸盐还显著缩短了含有各种抗凝药物的正常血浆的凝血时间，包括普通肝素、依诺肝素（一种低分子量肝素）、阿加曲班（一种直接凝血酶抑制剂）和利伐沙班（一种直接Xa因子抑制剂）。血栓弹力图显示，多磷酸盐使含有这些抗凝剂的全血的凝血动力学正常化，如凝块时间、凝块形成时间、α角和最大凝块硬度的变化所示。将预制因子Va加入血浆中的实验支持多磷酸盐通过加速因子V活化来拮抗这些药物的抗凝作用的观点。多聚磷酸盐还缩短了华法林患者血浆的凝血时间。这些结果表明，多磷酸盐可能具有逆转抗凝和治疗血友病患者出血事件的效用。
Polyphosphate is secreted by activated platelets and we recently showed that it accelerates blood clotting, chiefly by triggering the contact pathway and promoting factor V activation. We now report that polyphosphate significantly shortened the clotting time of plasmas from hemophilia A and B patients and that its procoagulant effect was additive to that of recombinant factor VIIa. Polyphosphate also significantly shortened the clotting time of normal plasmas containing a variety of anticoagulant drugs, including unfractionated heparin, enoxaparin (a low MW heparin), argatroban (a direct thrombin inhibitor) and rivaroxaban (a direct factor Xa inhibitor). Thromboelastography revealed that polyphosphate normalized the clotting dynamics of whole blood containing these anticoagulants, as indicated by changes in clot time, clot formation time, alpha angle and maximum clot firmness. Experiments in which pre-formed factor Va was added to plasma support the notion that polyphosphate antagonizes the anticoagulant effect of these drugs via accelerating factor V activation. Polyphosphate also shortened the clotting times of plasmas from warfarin patients. These results suggest that polyphosphate may have utility in reversing anticoagulation and in treating bleeding episodes in patients with hemophilia.
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