Haemostasis Research Unit, University College London, London, United Kingdom.
Thromb Res. 2012 Nov;130(5):775-9. doi: 10.1016/j.thromres.2011.12.023. Epub 2012 Jan 14.
Total hip/knee replacement surgery (THR/TKR respectively) is associated with an increased risk of venous thromboembolism. Dabigatran is recommended as a thromboprophylactic agent post orthopaedic surgery. The aim of this study was to assess the post-operative (Day-1 and Day-2) effect of prophylactic Dabigatran on: the thrombin generation (TG) assay; prothrombin fragment 1.2 (F1.2); thrombin-antithrombin complexes (TAT); D-dimer (D-D); and other coagulation parameters. METHODS AND SAMPLES: Nineteen patients (12 THR, 7 TKR) who received 110 mg dabigatran 4 hours post-operatively, then 220 mg the following day, were recruited. Blood was collected: pre-operatively (Pre-); peri-operatively (Peri-); 19 hours after 110 mg dabigatran (Day-1); and 17 hours after 220 mg dabigatran (Day-2). The TG assay was measured using the Calibrated Automated Thrombogram and a low concentration of tissue factor. Other coagulation parameters measured included activated partial thromboplastin time (APTT), thrombin-time (TT), ecarin-clotting time (ECT) and Hemoclot tests.
From Pre- to Peri-, ETP/peak-thrombin, F1.2, TAT and D-D increased significantly. From Peri- to Day-1 and Day-2: TAT reduced progressively; D-D increased; F1.2 did not change significantly; lag-time and time-to-peak prolonged; ETP/Peak-thrombin increased spuriously, due to Dabigatran interfering with the α-2 macroglobulin:thrombin complex in the TG assay. APTT, TT, ECT and Hemoclot increased progressively post-operatively; good correlations were seen between these tests.
The effect of dabigatran on the TG assay, showed a spurious increase in ETP and Peak-thrombin due to its interference with the TG assay. Dabigatran reduced TAT, but not F1.2, suggesting that thrombin was still being generated after surgery, but was blocked by Dabigatran.
全髋关节/膝关节置换术（THR/TKR 分别）与静脉血栓栓塞风险增加相关。达比加群被推荐为骨科手术后的预防性抗栓药物。本研究的目的是评估预防性达比加群在术后第 1 天（第 1 天）和第 2 天（第 2 天）对以下方面的影响：凝血酶生成（TG）测定；凝血酶片段 1.2（F1.2）；凝血酶-抗凝血酶复合物（TAT）；D-二聚体（D-D）；和其他凝血参数。方法和样本：19 名患者（12 例 THR，7 例 TKR）在术后 4 小时接受 110 毫克达比加群治疗，然后在第二天接受 220 毫克治疗。在术前（Pre-）；手术期间（Peri-）；110 毫克达比加群后 19 小时（第 1 天）；和 220 毫克达比加群后 17 小时（第 2 天）采集血液。使用校准自动血栓图和低浓度组织因子测量 TG 测定。测量的其他凝血参数包括活化部分凝血活酶时间（APTT）、凝血酶时间（TT）、埃卡林凝血时间（ECT）和 Hemoclot 测试。结果：从 Pre-到 Peri-，ETP/峰值凝血酶、F1.2、TAT 和 D-D 显著增加。从 Peri-到第 1 天和第 2 天：TAT 逐渐减少；D-D 增加；F1.2 变化不明显；lag-time 和达到峰值时间延长；由于达比加群在 TG 测定中干扰 α-2 巨球蛋白：凝血酶复合物，ETP/峰值凝血酶呈虚假增加。APTT、TT、ECT 和 Hemoclot 在术后逐渐增加；这些测试之间存在良好的相关性。结论：达比加群对 TG 测定的影响显示，由于其对 TG 测定的干扰，ETP 和峰值凝血酶出现虚假增加。达比加群降低了 TAT，但没有降低 F1.2，表明手术后仍有凝血酶生成，但被达比加群阻断。
