静脉血栓栓塞症抗凝靶点的研究现状与前景

Research Status and Prospect of Anticoagulants Targets for Venous Thromboembolism

静脉血栓栓塞症(VTE)包括深静脉血栓形成(DVT)和肺血栓栓塞症(PTE),其是住院患者非预期死亡的重要原因,已构成医疗质量和患者安全的潜在风险,且近10年来其造成的疾病负担逐年增加。目前,抗凝治疗是防治VTE的关键措施,尽管直接口服抗凝药(DOACs)较传统抗凝药更有效、安全且便利,但仍无法平衡治疗期间的抗栓与出血风险,故寻找更安全的抗凝靶点是VTE抗凝药研发的重点。本文以抗凝靶点为切入点总结了VTE抗凝药的研究现状,即凝血酶和凝血因子Ⅹa抑制剂虽已广泛用于临床,但适用人群受限,组织因子/凝血因子Ⅶa复合物、凝血因子Ⅷa及凝血因子Ⅸa抑制剂存在出血风险,凝血因子Ⅴa、凝血因子ⅩⅢa及凝血因子Ⅻa抑制剂的抗栓效果仍有待进一步评估,凝血因子Ⅺa可能是当前最有希望的抗凝靶点之一。

Venous thromboembolism(VTE),including deep venous thrombosis(DVT)and pulmonary thromboembolism(PTE),is an important cause of unexpected death in hospitalized patients.It has become a potential risk to medical quality and patient safety,and its disease burden has increased year by year in the past 10 years.At present,anticoagulant therapy is the key measure to prevent and treat VTE.Although direct oral anticoagulants(DOACs)are more effective,safe and convenient than traditional anticoagulants,they still cannot balance the antithrombotic and risk of bleeding during the treatment.Therefore,finding safer anticoagulant targets is the focus of VTE anticoagulant drug development.In this paper,the research status of VTE anticoagulants is summarized from the perspective of anticoagulant targets.Although thrombin and factorⅩa inhibitors have been widely used in clinical practice,but their application groups are limited.Tissue factor/factorⅦa compound,factorⅧa and factorⅨa inhibitors have the bleeding risk.The antithrombotic effects of factorⅤa,factorⅩⅢa and factorⅫa inhibitors still need to be further evaluated.FactorⅪa may be one of the most promising anticoagulant targets.