High dose factor VIIa improves clot structure and stability in a model of haemophilia B.
High dose factor VIIa improves clot structure and stability in a model of haemophilia B.
复制标题
高剂量因子 VIIa 可改善 B 型血友病模型中的凝块结构和稳定性。
DOI：
10.1111/j.1365-2141.2005.05820.x
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发表时间：
2005
期刊：
影响因子：
--
通讯作者：
Hoffman,Maureane
中科院分区：
文献类型：
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作者：
Wolberg,AlisaS;Allen,GeoffreyA;Monroe,DougaldM;Hedner,Ulla;Roberts,HaroldR;Hoffman,Maureane
因子IX （FIX）缺乏导致血友病B和高剂量重组活化因子VII （rFVIIa）可以减少出血。先前，我们发现FIX缺陷导致凝血酶生成速率降低和峰值。我们现在已经使用血浆和蛋白凝血模型来检验凝血酶生成的这些变化对纤维蛋白凝块结构和稳定性的影响。低FIX延迟了凝块形成的开始并降低了纤维蛋白聚合率。无FIX形成的血块由比正常更厚的纤维纤维组成。rFVIIa缩短血块形成时间，改善血块纤维结构。我们还通过在反应环境中加入组织纤溶酶原激活剂或纤溶酶来检测存在纤溶挑战时的凝块形成。在这些试验中，正常的FIX水平支持血栓形成；然而，在没有FIX的情况下，血栓不会形成。rfvia部分恢复血友病凝块形成。这些结果与凝血酶活化纤维蛋白溶解抑制剂的作用无关。我们的数据表明，rFVIIa通过增加凝血酶生成率来促进血友病患者的止血，从而促进结构正常的血块的形成，并改善内源性纤维蛋白溶解活性高的部位的血块形成和稳定性。
Factor IX (FIX) deficiency results in haemophilia B and high dose recombinant activated factor VII (rFVIIa) can decrease bleeding. Previously, we showed that FIX deficiency results in a reduced rate and peak of thrombin generation. We have now used plasma and anin vitrocoagulation model to examine the effect of these changes in thrombin generation on fibrin clot structure and stability. Low FIX delayed the clot formation onset and reduced the fibrin polymerisation rate. Clots formed without FIX were composed of thicker fibrin fibres than normal. rFVIIa shortened the clot formation onset time and improved the fibre structure of haemophilic clots. We also examined clot formation in the presence of a fibrinolytic challenge by including tissue plasminogen activator or plasmin in the reaction milieu. In these assays, normal FIX levels supported clot formation; however, clots did not form in the absence of FIX. rFVIIa partially restored haemophilic clot formation. These results were independent of the effects of the thrombin‐activatable fibrinolysis inhibitor. Our data suggest that rFVIIa enhances haemostasis in haemophiliacs by increasing the thrombin generation rate to both promote formation of a structurally normal clot and improve clot formation and stability at sites with high endogenous fibrinolytic activities.