利伐沙班抗凝治疗对人工膝关节置换术后下肢深静脉血栓形成的影响

Effect of rivaroxaban anticoagulant therapy on lower limb deep vein thrombosis after artificial knee arthroplasty

目的探讨利伐沙班抗凝治疗对人工膝关节置换术后下肢深静脉血栓形成(DVT)的影响。方法收集2020年6月-2022年6月于南方医科大学珠江医院接受人工膝关节置换术的144例患者的临床资料进行回顾性分析,患者术后均服用利伐沙班抗凝治疗,其中血小板>100×10~9/L开始抗凝的患者作为观察组(n=76),血小板>300×10~9/L开始抗凝的患者作为对照组(n=68)。采用倾向性评分匹配调整均衡性,两组各纳入56例,比较两组手术前后凝血指标[D-二聚体、血浆黏度(Pv)]的变化;Kaplan-Meier法绘制生存曲线分析两组术后30 d内发生DVT的情况。依据人工膝关节置换术后下肢DVT发生情况分为DVT组(n=36)与无DVT组(n=76)。采用logistic回归模型分析抗凝治疗前血小板水平与术后DVT的相关性;多因素logistic回归分析人工膝关节置换术后患者发生DVT的危险因素;R软件建立列线图,Bootstrap法重复抽样1000次进行验证,以ROC曲线下面积(AUC)和校准曲线评价区分度与准确度。结果匹配后观察组与对照组基线特征均衡(P>0.05)。Kaplan-Meier生存曲线显示,观察组30 d内DVT发生率低于对照组(P=0.043)。单因素分析结果显示,与无DVT组比较,DVT组BMI以及双侧膝关节置换、术中失血量≥400 ml、全身麻醉、使用骨水泥、三酰甘油≥1.7 mmol/L者比例明显增加,D-二聚体、血小板水平明显升高,PT明显缩短,APTT明显延长,差异均有统计学意义(P<0.05)。校正年龄、性别、BMI、三酰甘油、D-二聚体、PT、APTT相关混杂因素后,抗凝治疗前血小板水平仍是术后DVT的独立危险因素(OR=3.858,95%CI 1.849~6.054),且血小板从低到高水平五分位数组趋势性检验差异有统计学意义(P趋势<0.001)。多因素logistic回归分析结果显示,BMI≥25 kg/m^(2)、双侧膝关节置换术、全身麻醉、D-二聚体≥190μg/L、血小板≥300×10~9/L是人工膝关节置换术后患者发生DVT的危险因素(OR>1,P<0.05),而未使用骨水泥、PT≥12 s是其保护因素(OR<1,P<0.05)。列线图模型验证前后AUC分别为0.851(95%CI 0.773~0.912)和0.813(95%CI 0.736~0.894),校准曲线平均绝对误差均为0.015。结论人工膝关节置换术后血小板>100×10^(9)/L时应用利伐沙班抗凝治疗能够快速改善患者的凝血功能指标,降低DVT发生率。

Objective To investigate the effects of rivaroxaban anticoagulant therapy on lower deep venous thrombosis(DVT)after artificial knee arthroplasty.Methods One hundred and forty-four patients who received artificial knee replacement in the Zhujiang Hospital of Southern Medical University from June 2020 to June 2022 were retrospectively analyzed.All the patients received rivaroxaban anticoagulant treatment after surgery.Among them,the patients who started anticoagulant therapy at platelets>100×10^(9)/L were included in the observation group(n=76),and the patients who started anticoagulant at platelets>300×10^(9)/L were included in the control group(n=68).The propensity score matching was used to adjust the balance,and each group included 56 patients.The changes of coagulation markers[D-dimer and plasma viscosity(PV)]before and after operation were compared between the two groups.The survival curve was drawn by Kaplan-Meier method to analyze the occurrence of DVT in the two groups within 30 days after operation.According to the presence or absence of lower limb DVT events after knee arthroplasty,the patients were divided into DVT group(n=36)and non-DVT group(n=76).Logistic regression model was used to analyze the independent correlation between platelet level before anticoagulant therapy and postoperative DVT.Multivariate logistic regression analysis was used to analyze the risk factors of DVT after knee arthroplasty.The nomogram was established by R software and verified 1000 times by Bootstrap method.The area under ROC curve(AUC)and calibration curve were used to evaluate the discrimination and accuracy.Results After matching,the baseline characteristics of the observation group and the control group were balanced(P>0.05).Univariate analysis showed that compared with non-DVT group,BMI and the proportion of bilateral knee arthroplasty,intraoperative blood loss≥400 ml,general anesthesia,use of bone cement,and triacylglycerol≥1.7 mmol/L,and the levels of D-dimer and platelet increased,prothrombin time(PT)shortened,and activated partial thromboplastin time(APTT)extended in the DVT group(P<0.05).After adjusting the confounding factors of age,sex,BMI,triglyceride,D-dimer,PT and APTT,the platelet level before anticoagulant therapy was still an independent risk factor for postoperative DVT(OR=3.858,95%CI 1.849-6.054),and there was a significant difference in platelet trend test from low to high quintile(Ptrend<0.001).The results of multivariate logistic regression analysis showed that BMI≥25 kg/m^(2),bilateral knee arthroplasty,general anesthesia,D-dimer≥190μg,platelet≥300×10^(9)/L were risk factors for DVT after knee arthroplasty(OR>1,P<0.05),while not using bone cement and PT≥12 s were protective factors(OR<1,P<0.05).Before and after the verification of the nomogram,the AUC was 0.851(95%CI 0.773-0.912)and 0.813(95%CI 0.736-0.894),and the average absolute error of the calibration curve was 0.015.Conclusion The application of rivaroxaban anticoagulation therapy can quickly improve the coagulation function of patients with platelet>100×10^(9)/L after artificial knee replacement surgery and reduce the incidence of DVT.