Oswald Elgar, Velik-Salchner Corinna, Innerhofer Petra, Tauber Helmuth, Auckenthaler Thomas, Ulmer Hanno, Streif Werner
aDepartment of Anaesthesiology and Intensive Care Medicine bDepartment of Orthopedics cDepartment of Medical Statistics, Informatics and Health Economics dDepartment of Pediatrics and Adolescent Medicine, Innsbruck Medical University, Innsbruck, Austria.
Blood Coagul Fibrinolysis. 2015 Mar;26(2):136-44. doi: 10.1097/MBC.0000000000000203.
A prospective observational study was conducted in two clinical cohorts of patients to compare the effect of enoxaparin and rivaroxaban on rotational thromboelastometry (ROTEM), coagulation activation markers and thrombin generation.
A total of 188 consecutive patients scheduled for major orthopedic surgery receiving 40-mg enoxaparin subcutaneously or 10-mg rivaroxaban orally were evaluated. Blood samples were taken before induction of anesthesia and on day 4 after surgery [postoperative day 4 (pod 4)]. The extrinsically (EXTEM) and the intrinsically (INTEM) activated ROTEM assay, antithrombin, prothrombin fragments (F1 + 2), thrombin-antithrombin complex (TAT) and D-dimers were measured, and the thrombodynamic ratio (TDR) was calculated. Thrombin generation was determined using calibrated automated thrombography. To compare the groups, changes (Δ) in baseline versus pod 4 were calculated.
EXTEM clotting time (CT) increased more with rivaroxaban than with enoxaparin; values above the reference range were observed (median ΔEXTEM-CT 15 vs. 5 s, P ≤ 0.0001). The increase in INTEM-CT (values remained within the normal ranges) was slight with enoxaparin and significant with rivaroxaban; ΔINTEM-CT was comparable. EXTEM-TDR, unchanged with rivaroxaban, increased significantly with enoxaparin, whereas ΔINTEM-TDR was comparable. ΔAT, ΔF1 + 2 and ΔTAT were significantly lower in the rivaroxaban group. Endogenous thrombin potential (ETP), unchanged with rivaroxaban, decreased significantly with enoxaparin; the maximal rising slope (mean velocity rate index) decreased more with rivaroxaban.
Data show that prolonged CT in the extrinsic ROTEM and thrombin generation assays reflecting initiation and propagation of thrombin may be useful for detecting treatment with rivaroxaban. The significance of observed differences in markers of coagulation needs to be investigated further.
在两组临床患者队列中进行了一项前瞻性观察性研究，以比较依诺肝素和利伐沙班对旋转血栓弹力图（ROTEM）、凝血激活标志物和凝血酶生成的影响。
对总共188例计划接受大型骨科手术的连续患者进行评估，这些患者接受皮下注射40mg依诺肝素或口服10mg利伐沙班。在麻醉诱导前和术后第4天[术后第4天（pod 4）]采集血样。测量外源性（EXTEM）和内源性（INTEM）激活的ROTEM检测、抗凝血酶、凝血酶原片段（F1+2）、凝血酶-抗凝血酶复合物（TAT）和D-二聚体，并计算血栓动力学比率（TDR）。使用校准自动血栓形成描记法测定凝血酶生成。为比较两组，计算基线与pod 4之间的变化（Δ）。
利伐沙班组EXTEM凝血时间（CT）的增加幅度大于依诺肝素组；观察到高于参考范围的值（EXTEM-CT中位数变化为15 vs. 5秒，P≤0.0001）。依诺肝素组INTEM-CT的增加幅度较小（值仍在正常范围内），而利伐沙班组增加显著；ΔINTEM-CT相当。EXTEM-TDR在利伐沙班组无变化，在依诺肝素组显著增加，而ΔINTEM-TDR相当。利伐沙班组的ΔAT、ΔF1+2和ΔTAT显著更低。内源性凝血酶潜力（ETP）在利伐沙班组无变化，在依诺肝素组显著降低；最大上升斜率（平均速度率指数）在利伐沙班组下降幅度更大。
数据表明，在外源性ROTEM和反映凝血酶起始和传播的凝血酶生成检测中，CT延长可能有助于检测利伐沙班治疗。凝血标志物观察到的差异的意义需要进一步研究。
