血栓与抗凝治疗监测的靶向时代

The era of targeted monitoring thromboembolism and anti-coagulation therapy

直接口服抗凝药的出现一改抗凝治疗剂量优化繁复的局面，以其特异性作用降低了静脉血栓复发和严重出血风险。同时，一些经过药监注册的新型标志物开启了临床应用的新阶段，不仅为靶向抗凝提供了针对性的评估手段，而且也填补了判断进行性血液凝集的空白。临床医生自此得以采取＂总体凝血表现－有效抗凝剂量－凝血酶生成－纤维蛋白生成＂的分层式主线分析监测治疗，减少了既往交叉网络式凝血机制带来的困惑。从直接口服抗凝药的临床应用出发，分析了抗活化Ⅱ因子和抗活化Ⅹ因子活性评价抗凝有效性的优势，进而提出直接或间接反映凝血酶活化程度的凝血酶生成试验和凝血酶－抗凝血酶酶复合物是体现直接抗凝效果的重要参数，以及纤维蛋白单体作为纤维蛋白生成早期标志物对评价凝血酶受抑制程度的独特作用；讨论ⅩⅢ因子作为纤维蛋白形成过程的关键环节在出血病因分析中的潜在价值。新型标志物和手段有别于传统凝血指标评价多种凝集蛋白活性的综合表现，而是以反映单一靶标的活性或受抑制程度来准确分析抗凝疗效或血栓预后，从而将止血血栓检验带入了一个新时代。

The emergence of new oral anticoagulant （NOAC） reduced the risk of venous thromboembolism recurrence and major bleeding, with their specificity on inhibiting single coagulation factor, hence avoided frequent dose adjustment of classic anticoagulant therapy. Recently, A new stage was initialed by several new assays with their approval of SFDA in clinical application, either providing a targeted assessment on targeted anticoagulation, or filling the gaps between measurement and evaluating progressive blood coagulation. Clinicians could take stratified way- ＂global coagulation-effective dose of anticoagulant-thrombin generation-fibrin production＂ to monitor and treat in the major axis of coagulation, eliminating the confusion of cross-network-like coagulation mechanism previously. In this paper, focusing on characteristics of new oral anticoagulants, we interpret the advantages of anti-activated factor Ⅱ and anti-activated factor Ⅹ activity in evaluating anticoagulant efficacy, and then suggest thrombin generation test and thrombin-antithrombin complex these two important parameters to understand the inhibitory action of NOAC, which reflect the degree of thrombin activation directly or indirectly. Moreover, fibrin monomer play a unique role in assessment of thrombin inhibition, as an early marker of fibrinogen formation. Potential value of factor ⅩⅢ in bleeding etiology is also discussed for its essentiality in the process of fibrin formation. Different from traditional coagulation tests determining the comprehensive activity of a variety of coagulation proteins, new assays provide information on activity or inhibition of a single target in anticoagulation therapy to analyze the anticoagulant effect or prognosis of thromboembolism accurately, which leads hemostasis and thrombosis tests into a new era.