新型凝血因子Ⅺ抑制剂在静脉血栓栓塞症中的循证医学证据与研究进展

Evidence-based research and prognosis of novel coagulation factorⅪinhibitors in venous thromboembolism

血栓形成是静脉血栓栓塞症发生与进展的主要原因。抗凝治疗是静脉血栓栓塞症防治的基石,其发展主要经历了间接凝血酶抑制剂、直接凝血酶抑制剂、维生素K拮抗剂和新型口服抗凝药。尽管安全性较前改善,但出血风险仍是目前抗凝治疗不可忽略的不良反应,尤其是应用于高出血风险患者时。凝血通路的深入研究发现凝血因子Ⅺ不参与止血的启动,而主要是通过凝血酶的反馈激活促进血栓的生长和稳定,进一步研究发现抑制凝血因子Ⅺ可显著抑制血栓形成且仅轻微影响止血功能。近来多项研究证实了凝血因子Ⅺ抑制剂在膝关节置换术后患者静脉血栓栓塞症预防的有效性与安全性。此外,凝血因子Ⅺ抑制剂应用于高出血风险人群的研究进一步证实了其安全性。凝血因子Ⅺ抑制剂可能是未来十年极具潜力的抗凝药物。

Thrombosis is the main cause of the development and progression of venous thromboembolism(VTE).Anticoagulant therapy is the cornerstone for the prophylaxis and treatment of VTE,and it has evolved mainly through indirect thrombin inhibitors,direct thrombin inhibitors,vitamin K antagonists and new oral anticoagulants.Although safety is improving,the risk of bleeding remains a non-negligible side effect of current anticoagulation therapy,especially in patients with higher bleeding risk.Studies of the coagulation pathway have found that FXI is not involved in the initiation of hemostasis,but promotes thrombus growth and stabilization primarily through feedback activation of FⅪby thrombin.Further studies have found that inhibition of FⅪsignificantly inhibits thrombus formation and only affects hemostasis slightly.Recent studies have confirmed the efficacy and safety of FⅪinhibitors in the prevention of VTE in patients after knee replacement.In addition,the safety of FⅪinhibitors has been further confirmed by the studies of FⅪinhibitors in people with higher bleeding risk.FⅪinhibitors may be the most promising anticoagulant drugs in the next decade.