Helin Tuukka A, Virtanen Lauri, Manninen Mikko, Leskinen Jarkko, Leppilahti Juhana, Joutsi-Korhonen Lotta, Lassila Riitta
Coagulation Disorders Unit, Clinical Chemistry, HUSLAB Laboratory Services, Helsinki University Hospital, Helsinki, Finland.
Coagulation Disorders Unit, Hematology and Clinical Chemistry (HUSLAB Laboratory Services), Helsinki University Hospital, and University of Helsinki, POB 340, 00029, Helsinki, Finland.
J Thromb Thrombolysis. 2017 May;43(4):562-569. doi: 10.1007/s11239-017-1492-2.
Factor Xa inhibitors (FXaI) apixaban and rivaroxaban are used for thromboprophylaxis after major elective orthopaedic surgery. Because few patient sample studies exist, we postoperatively assessed patients undergoing unilateral total hip arthroplasty, including 22 treated with apixaban (2.5 mg BID) and 20 treated with rivaroxaban (10 mg OD). We collected blood samples before and 3 h after drug intake at 4 time points, preoperatively, as well as on day 1, week 1 (day 2-8) and day 28 post-operation. APTT and PT were immediately analysed. Calibrated anti-FXa activity, Russel's Viper Venom Time (RVVT) and thrombin generation (TG; Calibrated Automated Thrombogram) captured the effects of FXaI on coagulation and TG. APTT and PT remained within the reference interval throughout, and did not correlate with FXaI levels (PT R = 0.44, APTT R = 0.07). Mean apixaban concentration at the peak varied by eightfold (19-153 ng/mL), but rivaroxaban only by 1.5-fold (111-183 ng/mL). Rivaroxaban, but not apixaban prolonged RVVT at peak levels. Both FXaIs had a prolonged lag time of TG (p < 0.001). Rivaroxaban decreased ETP peak at all time points and reached a minimum at day 28 (540 nM/min at rivaroxaban 184 ng/mL, p < 0.001), while rivaroxaban trough levels were low and ETP values normal. However, with apixaban, after an initial decrease, ETP did not differ between peak and trough levels until decreasing on day 28 at peak (990 nM/min at apixaban 112 ng/mL, p = 0.005). In conclusion, due to different dosing and pharmacology rivaroxaban and apixaban distinctly inhibited TG under postoperative conditions.
凝血因子Xa抑制剂（FXaI）阿哌沙班和利伐沙班用于大型择期骨科手术后的血栓预防。由于患者样本研究较少，我们对接受单侧全髋关节置换术的患者进行了术后评估，其中22例接受阿哌沙班治疗（2.5毫克，每日两次），20例接受利伐沙班治疗（10毫克，每日一次）。我们在术前、术后第1天、第1周（第2 - 8天）和第28天这4个时间点，在服药前和服药后3小时采集血样。立即分析活化部分凝血活酶时间（APTT）和凝血酶原时间（PT）。校准的抗FXa活性、蝰蛇毒时间（RVVT）和凝血酶生成（TG；校准自动凝血图）反映了FXaI对凝血和TG作用。APTT和PT始终保持在参考区间内，且与FXaI水平无相关性（PT相关系数R = 0.44，APTT相关系数R = 0.07）。阿哌沙班峰值时的平均浓度变化了8倍（19 - 153纳克/毫升），但利伐沙班仅变化了1.5倍（111 - 183纳克/毫升）。利伐沙班而非阿哌沙班在峰值水平延长了RVVT。两种FXaI均延长了TG的延迟时间（p < 0.001）。利伐沙班在所有时间点均降低了内源性凝血酶潜能（ETP）峰值，并在第28天达到最低值（利伐沙班184纳克/毫升时为每分钟540纳米摩尔，p < 0.001），而利伐沙班谷值水平较低且ETP值正常。然而，对于阿哌沙班，在最初下降后，ETP在峰值和谷值水平之间无差异，直到第28天峰值时下降（阿哌沙班112纳克/毫升时为每分钟990纳米摩尔，p = 0.005）。总之，由于给药方式和药理学不同，利伐沙班和阿哌沙班在术后条件下对TG的抑制作用明显不同。
