全膝关节置换术应用氨甲环酸后序贯应用阿哌沙班预防静脉血栓栓塞症的有效性和安全性

Efficacy and safety of apixaban in prevention of venous thromboembolism after application of tranexamic acid in total knee arthroplasty

背景：全膝关节置换术（TKA）围手术期常规应用抗凝药物已形成共识,但目前未见应用氨甲环酸（TXA）后序贯应用阿哌沙班预防静脉血栓栓塞症（VTE）的相关研究。目的：评价TKA应用TXA后序贯应用阿哌沙班预防VTE的有效性和安全性。方法：2013年10月至2013年12月共纳入100例行初次单侧TKA患者,随机分为两组,每组各50例,A组为低分子肝素组,B组为阿哌沙班组,两组均在松止血带前5-10 min TXA 15 mg/kg静脉滴注,术后6-12 h在每小时引流量〈30 ml时给予低分子肝素0.2 m（l2000 Axa IU,依诺肝素钠,赛诺菲公司提供）或阿哌沙班2.5 mg（美国施贵宝制药有限公司提供）,两者最迟使用时间不超过术后12 h,以后按常规剂量使用至术后14 d;比较分析两组术后引流量、总失血量、深静脉血栓（DVT）和肺栓塞（PE）发生率、大出血事件发生率、临床相关非大出血事件发生率和凝血功能变化。结果：A组引流量（226.1±79.3）ml,B组引流量（232.1±76.1）ml,相比较无统计学差异（P=0.726）;A组总失血量（916.3±192.6）ml,B组总失血量（887.2±213.7）ml,相比较无统计学差异（P=0.701）;术后5d两组均未发生DVT,A组发生肌间静脉血栓3例,B组发生肌间静脉血栓2例,相比较无统计学差异（P=0.674）;两组住院期间均未发生PE疑似病例;术后1个月和3个月门诊或电话随访未见症状性DVT和PE病例;两组均未发生大出血事件;A组和B组均发生临床相关非大出血事件6例,相比较无统计学差异（P=0.940）;术后1d、3d和5d两组患者的PT和APTT均较术前延长,组间比较以上时间点均无统计学差异（P〉0.05）。结论：TKA围手术期应用TXA后序贯应用阿哌沙班和低分子肝素预防VTE均是安全有效的。

Background： There is broad consensus on the application of anticoagulant drugs after total knee arthroplasty（TKA）. However, there is no research about the efficacy and safety of the sequential application of apixaban followed by tranexamic acid（TXA） in TKA for the prevention of venous thromboembolism（VTE）.Objective： To explore the efficacy and safety of apixaban to prevent VTE after using TXA in TKA.Methods： One hundred patients undergoing unilateral primary TKA between October 2013 and December 2013 were randomly divided into two groups（n=50）： low molecular weight heparin（LMWH） group and apixaban group. TXA 15 mg/kg was given by intravenous drip before the end of the operation for 5-10 min in both groups. Then 0.2 ml LMWH and 2.5 mg apixaban were administrated at 6-12 h after the operation if the drainage was less than 30 ml/h, in the two groups, respectively. After that LMWH and apixaban were used routinely until 14 d postoperatively. Postoperative wound drainage, total blood loss, coagulation and the incidence of deep venous thrombosis（DVT）, pulmonary embolism（PE）, major bleeding events and clinic-related non-major bleeding events were compared between two groups.Results： The mean wound drainage was（226.1±79.3） ml in the LMWH group and（232.1±76.1） ml in the apixaban group,and there was no significant difference between groups（P=0.726）. Neither was the total blood loss（[916.3 ± 192.6] ml vs[887.2±213.7] ml, P=0.701）. No DVT was found within 5 days after operation. Venous thrombosis occurred in 3 patients of the LWMH group and 2 patients of the apixaban group（P=0.674）. There was no symptomatic DVT or PE during follow-up（1 and 3 months postoperatively）. Major bleeding events were not found in either LWMHs group or apixaban group. Clinic-related non- major bleeding events occurred in 6 patients of each group（P=0.940）. Both PT and APTT lengthened in both groups on day 1, 3 and 5 as compared with preoperative ones, but there were no significant differences in these parameters between groups（P〉0.05）.Conclusions： Both LWMH and apixaban are effective and safe to prevent VTE after using TXA in TKA.