应用抗活化因子X活性试验评估合并肾功能不全的非瓣膜性房颤患者口服利伐沙班的出血风险

Evaluate the bleeding risk of oral rivaroxaban in patients with non-valvular atrial fibrillation and renal insufficiency by anti-Xa activity test

目的 探讨合并肾功能不全的非瓣膜性房颤(AF)患者服用利伐沙班抗凝治疗期间,应用抗活化因子X活性(anti-FXa)试验监测的利伐沙班血药浓度与临床相关出血事件的相关性。方法 纳入2020年1月~2021年1月在我院住院或门诊确诊为非瓣膜性AF且合并肾功能不全患者96例,均选择利伐沙班进行抗凝治疗。根据随访期间是否发生临床相关出血事件将所有患者分为出血组(21例)和未出血组(75例)。比较两组患者一般临床资料、实验室检查指标及anti-FXa试验相关数据。采用多因素logistic回归分析评估临床相关出血事件发生的影响因素;采用受试者工作特征(ROC)曲线分析利伐沙班血药浓度评估临床相关出血事件发生风险的诊断效能。结果 所有患者随访期间共发生临床相关出血事件21例[21.9%,其中临床相关大出血1例(1.0%),临床相关非大出血事件20例(20.8%)]。出血组患者血清Ccr显著低于未出血组(P<0.05)。服药后3 h患者利伐沙班血药浓度及凝血酶原时间(PT)、活化部分凝血活酶时间(APTT)和国际标准化比率(INR)均显著高于服药后24 h(P<0.05)。出血组患者服药后3 h利伐沙班血药浓度峰值及服药后24 h利伐沙班血药浓度谷值均显著高于同一服药时间段未出血组,服药后3 h PT、APTT和INR均显著高于同一服药时间段未出血组;未出血组患者服药后24 h利伐沙班血药浓度及PT均显著低于同组服药后3 h,FX:C高于同组服药后3 h;出血组患者服药后24 h利伐沙班血药浓度显著低于同组服药后3 h,FX:C高于同组服药后3 h(P<0.05)。多因素logistic回归分析结果显示,利伐沙班血药浓度峰值和Ccr均为临床相关出血事件发生的独立影响因素(P<0.05)。ROC曲线分析结果显示,取利伐沙班血药浓度峰值277.9 ng/ml作为最佳截断值时曲线下面积(AUC)为0.843,预测合并肾功能不全的非瓣膜性AF患者临床相关出血事件发生的敏感度为0.905,特异度为0.707。结论 Anti-FXa试验监测利伐沙班血药浓度可用于评估合并肾功能不全的非瓣膜性AF患者服用利伐沙班抗凝治疗期间临床相关出血事件的发生风险。

Objective To investigate the correlation between rivaroxaban plasma concentration measured by anti-Xa activity test(anti-FXa) test and clinically relevant bleeding events in patients with non-valvular atrial fibrillation(AF) and renal insufficiency during anticoagulant therapy with rivaroxaban.Methods A total of 96 patients diagnosed with non-valvular AF and renal insufficiency in our hospital from January 2020 to January 2021 were enrolled,which received rivaroxaban for anticoagulation therapy.All patients were divided into bleeding group(21 cases) and non-bleeding group(75 cases) according to whether clinically relevant bleeding events occurred during the follow-up period.General clinical data,laboratory indicators and anti-FXa test data of two groups were collected.Multivariate logistic regression analysis was used to evaluate the influencing factors of clinically relevant bleeding events;Receiver operating characteristic(ROC) curve was used to analyze the diagnostic performance of rivaroxaban plasma concentration in predicting the risk of clinically relevant bleeding events.Results A total of 21 cases of clinically relevant bleeding events occurred in all patients during the follow-up period[21.9%,including 1 case of clinically relevant major bleeding event(1.0%) and 20 cases of relevant non-major bleeding events(20.8%)].Serum Ccr in bleeding group was significantly lower than that in non-bleeding group(P<0.05).Blood concentration,prothrombin time(PT),activated partial thromboplastin time(APTT),international standard ratio(INR) of rivaroxaban at 3 h after administration were significantly higher than those at 24 h after administration(P<0.05).The peak blood concentration of rivaroxaban at 3 h after administration and the trough blood concentration of rivaroxaban at 24 h after administration in bleeding group were significantly higher than those in non-bleeding group at the same period of administration;PT,APTT and INR at 3 h after administration in bleeding group were significantly higher than those in non-bleeding group at the same period of administration;In non-bleeding group,the plasma concentration and PT of rivaroxaban at 24 h after administration were significantly lower than those at 3 h after administration,and FX:C was higher than that at 3 h after administration;In bleeding group,the plasma concentration of rivaroxaban at 24 h after administration was significantly lower than that at 3 h after administration,and FX:C was higher than that at 3 h after administration(P<0.05).Multivariate logistic regression analysis showed that plasma concentration of rivaroxaban and Ccr were independent influencing factors for clinically relevant bleeding events(P<0.05).ROC curve analysis showed that when the peak blood concentration of rivaroxaban was 277.9 ng/ml,area under the curve(AUC) was 0.843,sensitivity and specificity for predicting clinically relevant bleeding events were 0.905 and 0.707 respectively.Conclusion The plasma concentration of rivaroxaban monitored by anti-FXa assay can be used to evaluate the risk of clinically relevant bleeding events during rivaroxaban anticoagulation therapy in patients with non-valvular atrial fibrillation complicated with renal dysfunction.