Department of Medicine, Division of Haematology, Coagulation Unit, Karolinska University Hospital and Karolinska Institutet, Stockholm, Sweden.
Department of Medicine, Division of Haematology, Coagulation Unit, Karolinska University Hospital and Karolinska Institutet, Stockholm, Sweden; Department of Molecular Medicine and Surgery, Karolinska Institutet, Stockholm, Sweden.
Thromb Res. 2019 Jun;178:34-40. doi: 10.1016/j.thromres.2019.03.022. Epub 2019 Apr 1.
Venous thromboembolism (VTE) affects approximately 1 per 1000 persons annually. Although patients are increasingly treated with direct oral anticoagulants, many patients continue to be anticoagulated with vitamin K antagonists (VKA). The most important adverse events during VKA treatment, bleeding and the risk of recurrent VTE, are difficult to predict. Global haemostatic assays, such as thrombin generation assays and the viscoelastic whole blood tests thromboelastography (TEG) and thromboelastometry (ROTEM), allow a comprehensive assessment of haemostasis and could potentially predict such side effects. In the present study we compared results from thrombin generation (Calibrated Automated Thrombogram and Innovance ETP assays) and TEG and ROTEM in 84 warfarin-treated patients with primary or recurrent VTE and 87 healthy controls. VKA treatment lead to lagtime prolongation and a lower overall thrombin production, which correlated strongly with INR (Pearson r = 0.89 and r = -0.85, respectively). The reduced thrombin generation of VKA-treated patients was accurately reflected by tissue-factor activated ROTEM (EXTEM) clotting time prolongation (vs. CAT lagtime, r = 0.87). Clot strength or clot formation kinetics were only weakly affected by thrombin generation. Intrinsic pathway activated TEG or ROTEM (INTEM) were not sensitive to the reduced thrombin generation. In conclusion, patients anticoagulated with VKA after VTE showed a reduced plasma thrombin generation that was accurately reflected by tissue factor activated ROTEM. ROTEM provided additional information to thrombin generation, including clot formation kinetics and strength.
静脉血栓栓塞症（VTE）每年影响约每 1000 人中的 1 人。尽管越来越多的患者接受直接口服抗凝剂治疗，但许多患者仍继续接受维生素 K 拮抗剂（VKA）抗凝治疗。VKA 治疗期间最重要的不良事件，即出血和复发性 VTE 的风险，难以预测。全球止血检测，如凝血酶生成检测和粘弹性全血检测血栓弹力描记术（TEG）和血栓弹力图（ROTEM），可以全面评估止血情况，并有可能预测此类副作用。在本研究中，我们比较了 84 例接受华法林治疗的初发性或复发性 VTE 患者和 87 例健康对照者的凝血酶生成（Calibrated Automated Thrombogram 和 Innovance ETP 检测）和 TEG 和 ROTEM 的结果。VKA 治疗导致 lagtime 延长和整体凝血酶生成减少，与 INR 密切相关（Pearson r = 0.89 和 r = -0.85）。VKA 治疗患者凝血酶生成减少被组织因子激活的 ROTEM（EXTEM）凝血时间延长准确反映（与 CAT lagtime 相比，r = 0.87）。凝块强度或凝块形成动力学仅受凝血酶生成的微弱影响。内在途径激活的 TEG 或 ROTEM（INTEM）对凝血酶生成减少不敏感。总之，VTE 后接受 VKA 抗凝的患者表现出血浆凝血酶生成减少，这被组织因子激活的 ROTEM 准确反映。ROTEM 提供了比凝血酶生成更多的信息，包括凝块形成动力学和强度。
