Tissue factor pathway inhibitor in activated prothrombin complex concentrates (aPCC) moderates the effectiveness of therapy in some severe hemophilia A patients with inhibitor.
Tissue factor pathway inhibitor in activated prothrombin complex concentrates (aPCC) moderates the effectiveness of therapy in some severe hemophilia A patients with inhibitor.
复制标题
活化凝血酶原复合物浓缩物 (aPCC) 中的组织因子途径抑制剂可调节某些含有抑制剂的严重甲型血友病患者的治疗效果。
DOI：
10.1007/s12185-014-1572-4
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发表时间：
2014
期刊：
影响因子：
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通讯作者：
Shima M.
中科院分区：
文献类型：
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作者：
Ogiwara K;Nogami K;Matsumoto T;Shima M.
一些已经开发出抑制剂的血友病A患者在每日剂量后对激活的凝血酶原复合体(APCC)的反应较差，但其背后的机制(S)仍不清楚。我们审查了两个有代表性的案例。在病例1中，我们发现改用重组因子VIIa(RFVIIa)治疗更有效，对APCC的反应在~2周内恢复。组织因子(TF)触发的凝血酶生成延迟时间延长，峰值凝血酶降低，这种损害集中在组织因子途径抑制剂(TFPI)上。输注APCC后血浆游离TFPI升高，而rFVIIa对此无影响。TFPI在2-3周内恢复到正常范围。从对APCC反应差或好(APCC-差或APCC-好)和对rFVIIa反应好(FVIIa-好)的患者获得的血浆显示，两组APCC的游离TFP I水平都增加了，但FVIIa-好的患者没有增加。APCC差的患者输注前后的TFPI水平显著高于APCC好的患者。在反应样本中加入抗TFPI抗体后，APCC-穷人的凝血酶峰值比APCC-Good的增加更大，表明APCC-穷人的TFPI活性更高。APCC中游离TFPI的含量与血浆中游离TFPI水平的升高相对应。总而言之，APCC中的TFPI抑制了凝血酶的生成，在这种情况下治疗效果的降低似乎与TFPI的活性有关。
Some hemophilia A patients who have developed inhibitors are poorly responsive to activated prothrombin complex concentrates (aPCC) after daily dosage, but the mechanism(s) underlying this remain unknown. We examined two representative cases. In case 1, we found that changing to recombinant factor VIIa (rFVIIa) therapy was more effective, and the response to aPCC was restored within ~2 weeks. Tissue factor (TF)-triggered thrombin generation demonstrated a prolonged lag-time and decreased peak thrombin, and this impairment was focused on TF pathway inhibitor (TFPI). Plasma-free TFPI was elevated post-infusion of aPCC, while this was unaffected by rFVIIa. TFPI returned to normal range within 2–3 weeks. Plasmas obtained from patients with poor or good response to aPCC (aPCC-poor or aPCC-good), and good response to rFVIIa (FVIIa-good) demonstrated that free TFPI levels are increased in both aPCC groups, but not in FVIIa-good. TFPI levels pre- and post-infusion in aPCC-poor were significantly higher than those in aPCC-good. Addition of anti-TFPI antibody to the reaction samples demonstrated a greater increase of peak thrombin in aPCC-poor compared to aPCC-good, showing the higher TFPI activity in aPCC-poor. Free TFPI contained in aPCC corresponded to the increasing levels in plasma. In conclusion, TFPI in aPCC attenuated thrombin generation, and the reduced effectiveness of therapy in these circumstances appeared to be related to TFPI activity.