达比加群服药患者出血风险的实验室检测

Laboratory measurement of bleeding risk for patients receiving Dabigatran

目的观察常规凝血试验结果与血浆达比加群浓度的相关性,寻找合适的试验用于监测达比加群服药患者的出血风险。方法分析北京大学第三医院2015年至2017年使用达比加群抗凝的49名非瓣膜性心房颤动(NVAF)患者的临床资料,并计算其出血发生率。收集20名健康志愿者的血浆,制成正常混合血浆(NPP),分别向1 m L NPP中加入0~1 000 ng/m L浓度梯度的达比加群,检测凝血酶原时间(PT)、活化部分凝血活酶时间(APTT)、凝血酶时间(TT)、纤维蛋白原(Fib)和稀释蝰蛇毒时间(dRVVT)。另外收集3名健康志愿者的新鲜全血,做相同的加药处理后进行血栓弹力图试验(TEG)。结果服用达比加群的NVAF患者的出血发生率高达28.6%,以消化道出血居多。APTT、dRVVT、TEG的R时间(R)和凝血指数(CI)结果与血浆达比加群浓度相关性良好,其中,dRVVT的敏感性最强,APTT次之,R和CI敏感性较差。结论 APTT和dRVVT在监测达比加群出血事件方面具有重要意义,将有助于临床寻找合适的停药时机,减少出血事件的发生。

Objective To observe the correlation between conventional coagulation tests and Dabigatran concentration in order to find proper test method to predict the bleeding risk of patients receiving Dabigatran. Methods The clinical data of forty-nine non-valvular atrial fibrillation（ NVAF） patients who took Dabigatran in Peking University Third Hospital from 2015 to 2017 were analyzed and the bleeding rates were calculated. The plasma samples from twenty healthy volunteers were collected and mixed up into normal pooled plasma（ NPP）. Different doses of active Dabigatran were mixed with NPP,making Dabigatran concentrations from 0 to 1 000 ng/m L.Prothrombin time（ PT）,activated partial thromboplastin time（ APTT）,thrombin time（ TT）,fibrinogen（ Fib） and diluted Russell viper venom time（ dRVVT） were determined. Fresh whole blood samples from three normal volunteers were collected and mixed with Dabigatran in the same way to perform thromboelastogram（ TEG）. Results The total bleeding rate of NVAF patients receiving Dabigatran was 28. 6%,among which gastrointestinal bleeding accounts for the most. APTT,dRVVT,R time（ R） and clot index（ CI）showed a good linear correlation with Dabigatran concentration. The sensitivity of dRVVT was the best,followed by APTT. R and CI showed low sensitivity compared with APTT and dRVVT. Conclusion APTT and dRVVT should be good parameters for monitoring the bleeding risk of Dabigatran and helpful for physicians to choose proper point-in-time for withdrawal of Dabigatran and reduce bleeding events.