Factor (F)VIII/VIIa enhances global haemostatic function in the co-presence of bypassing agents and FVIII among patients with haemophilia A with inhibitor
Factor (F)VIII/VIIa enhances global haemostatic function in the co-presence of bypassing agents and FVIII among patients with haemophilia A with inhibitor
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在具有抑制剂的 A 型血友病患者中，旁路药物和 FVIII 共存时，因子 (F)VIII/VIIa 增强整体止血功能
DOI：
10.1111/bjh.15209
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发表时间：
2018
期刊：
影响因子：
--
通讯作者：
Shima M
中科院分区：
文献类型：
--
作者：
Nogami K;Matsumoto T;Yada K;Ogiwara K;Furukawa S;Shida Y;Takeyama M;Shima M
抗凝治疗对于血友病A伴抑制剂（PWHA‐inh）患者的止血管理至关重要，但治疗效果不一致。我们以前报道过活化凝血酶原复合物浓缩物（aPCC）在体外激活因子（F）VIII，并主要由aPCC中所含的活化FVII（FVIIa）介导。我们已经扩展了这些研究，以使用Ca 2+触发的旋转血栓弹性测定法评估在aPCC和FVIII共存的情况下18 PWHA-inh的全血中的总体凝血。与单独aPCC相比，存在aPCC（0.05iu/ml）和重组（r）FVIII（1 iu/ml）的体外凝血时间（CT）缩短（P<0.01）。观察到rFVIII的这些增强作用，与识别抑制剂表位无关;然而，凝块形成时间和“θ”角无显著差异。在输注aPCC（70 - 80 iu/kg）后7次PWHA-inh的样本中，与不存在rFVIIIex相比，存在rFVIIIex时仅CT缩短（P<0·05），表明活性增强集中在凝血起始阶段。此外，rFVIIa和rFVIII共存的实验表明，FVIII仅加速CT。我们得出结论，FVIII/FVIIa相关凝血机制通过旁路药物和FVIII在PWHA-inh中的共同存在增强了整体止血功能。
Bypassing therapy is essential for the haemostatic management of patients with haemophilia A with inhibitor (PWHA‐inh), but the therapeutic effects are inconsistent. We previously reported that activated prothrombin complex concentrates (aPCC) activated factor (F)VIIIin vitro,and was mediated mainly by the activated FVII (FVIIa) contained in aPCC. We have extended those studies to assess global coagulation in whole blood from 18 PWHA‐inh in the co‐presence of aPCC and FVIII using Ca2+‐triggered rotational thromboelastometry. The clot times (CTs) in the presence of both aPCC (0·05 iu/ml) and recombinant (r)FVIII (1 iu/ml)ex vivowere shortened compared to the aPCC alone (P<0·01). These enhancing effects of rFVIII were observed, irrespective of recognizing inhibitor epitopes; however, the clot formation time and ‘α’‐angle were not significantly different. In samples from 7 PWHA‐inh post‐infusion of aPCC (70‐80 iu/kg), only the CTs were shortened in the presence of rFVIIIex vivocompared to its absence (P<0·05), indicating that the enhanced activity centred on the initiation phase of coagulation. Furthermore, experiments in the co‐presence of rFVIIa and rFVIII demonstrated that FVIII accelerated only the CTs. We concluded that FVIII/FVIIa‐related coagulation mechanism enhanced global haemostatic function by the co‐presence of bypassing agents and FVIII in PWHA‐inh.