Ragni Margaret V
1Department of Medicine, Division of Hematology/Oncology, University of Pittsburgh, Pittsburgh, PA.
Hematology Am Soc Hematol Educ Program. 2013;2013:44-51. doi: 10.1182/asheducation-2013.1.44.
What is the correct use of established clotting factors, prothrombin complex concentrates (PCCs), and activated factor VII in bleeding complications of trauma, surgery, and old and new oral anticoagulants? How will new clotting factors, specifically the long-acting factors, change the hemostatic management of coagulation deficiency disorders? From bench to bedside, comparative coagulation studies and clinical trials of modified clotting factors are providing insights to help guide hemostatic management of congenital and acquired bleeding disorders. Comparative thrombin-generation studies and preclinical and clinical trials suggest that PCCs and fresh-frozen plasma are effective in reversing the anticoagulant effects of warfarin, yet there are few data to guide reversal of the new oral anticoagulants dabigatran and rivaroxaban. Although coagulation studies support the use of PCCs to reverse new oral anticoagulants, correlation with clinical response is variable and clinical trials in bleeding patients are needed. For congenital bleeding disorders, exciting new technologies are emerging from the bench. Data from clinical trials of molecularly modified coagulation factors with extended half-lives suggest the possibility of fewer infusions, reduced bleeds, and better quality of life in persons with hemophilia. Preclinical studies of other novel prohemostatic approaches for hemophilia and other congenital coagulation disorders include RNA interference silencing of antithrombin, monoclonal anti-tissue factor pathway inhibitor (anti-antibody, anti-tissue factor pathway inhibitor) aptamer, bispecific anti-IXa/X antibody, and fucoidans. Understanding the comparative coagulation studies of established prohemostatic agents, the pharmacokinetics of new long-acting clotting factors, and their correlation with bleeding outcomes will provide opportunities to optimize the hemostatic management of both congenital and acquired hemostatic disorders.
在创伤、手术以及新旧口服抗凝剂引起的出血并发症中，已有的凝血因子、凝血酶原复合物浓缩剂（PCCs）和活化凝血因子VII的正确用法是什么？新型凝血因子，特别是长效因子，将如何改变凝血功能缺陷疾病的止血管理？从实验室到临床，对改良凝血因子的比较凝血研究和临床试验正在提供见解，以帮助指导先天性和获得性出血性疾病的止血管理。比较凝血酶生成研究以及临床前和临床试验表明，PCCs和新鲜冷冻血浆可有效逆转华法林的抗凝作用，但几乎没有数据可指导新型口服抗凝剂达比加群和利伐沙班的逆转。尽管凝血研究支持使用PCCs来逆转新型口服抗凝剂，但与临床反应的相关性存在差异，需要对出血患者进行临床试验。对于先天性出血性疾病，实验室正在涌现令人兴奋的新技术。分子修饰的半衰期延长的凝血因子的临床试验数据表明，血友病患者可能减少输注次数、减少出血并提高生活质量。针对血友病和其他先天性凝血障碍的其他新型促止血方法的临床前研究包括抗凝血酶的RNA干扰沉默、单克隆抗组织因子途径抑制剂（抗抗体，抗组织因子途径抑制剂）适体、双特异性抗IXa/X抗体和岩藻聚糖。了解已有的促止血药物的比较凝血研究、新型长效凝血因子的药代动力学及其与出血结局的相关性，将为优化先天性和获得性止血障碍的止血管理提供机会。
