利伐沙班与低分子肝素联合华法林预防脾切除术后PVST形成的随机对照研究

Rivaroxaban versus low-molecular weight heparin plus warfarin prevents portal vein system thrombosis after splenectomy and pericardial devascularization:A randomized clinical trial

目的探讨利伐沙班预防肝硬化患者脾切除、贲门周围血管离断术后门静脉系统血栓(PVST)形成的安全性和有效性。方法76例接受脾切除、贲门周围血管离断术的患者随机分为研究组(n=38)和对照组(n=38)。研究组术后予以利伐沙班10 mg口服,1次/d,共口服30 d。对照组术后予以低分子肝素(LMWH)5000 IU皮下注射,2次/d,共注射5 d,同时予以华法林(起始剂量2.5 mg)口服,1次/d,共口服30 d。两组患者术后均定期复查,随访1年。比较两组患者术后PVST发生率、肝功及凝血功能恢复情况,以及肝功失代偿、肝癌发生、活动性出血发生率等安全性指标。结果利伐沙班组共计18例(47.4%)发生PVST,低分子肝素联合华法林组29例(76.3%)发生PVST(P=0.024)。利伐沙班组术后1年PVST发生率明显低于低分子肝素联合华法林组(F=7.852,P=0.007)。组内比较显示,利伐沙班组患者肝功能从术后21 d至术后1个月逐渐改善,凝血功能从术后2个月起改善。低分子肝素联合华法林组患者肝功能从术后1个月至术后2个月逐渐改善,凝血功能从术后4个月起改善。两组之间在肝功失代偿、肝癌发生、活动性出血发生率等安全性指标方面差异无统计学意义(P均>0.05)。结论与低分子肝素联合华法林治疗相比,预防性使用利伐沙班可显著降低肝硬化患者脾切除、贲门周围血管离断术后PVST的发生率;安全性较好;患者肝功能和凝血功能恢复至正常水平所需时间更短。

Objective To evaluate the safety and efficacy of rivaroxaban in preventing portal vein system thrombosis(PVST)in patients with liver cirrhosis after splenectomy and pericardial devascularization.Methods Totally 76 cirrhotic patients underwent splenectomy and pericardial devascularization were randomly assigned to rivaroxaban treatment group(n=38)or low-molecular weight heparin(LMWH)plus warfarin treatment group(n=38).The experimental group was given rivaroxaban 10 mg orally,once a day,for 30 days.The control group was given subcutaneous injection of 5000 IU low molecular weight heparin(LMWH)twice a day for 5 days and warfarin(initial dose 2.5 mg)orally once a day for 30 days.Both groups were followed up for 1 year.We compared the two groups in the incidence of PVST,recovery of liver function and coagulation function,decompensation of liver function,incidence of liver cancer,and active bleeding.Results Totally 18 patients(47.4%)in rivaroxaban group developed PVST,compared with 29 patients(76.3%)in LMWH plus warfarin group(P=0.024).The incidence of PVST during the first year after operation was significantly lower in rivaroxaban group than in LMWH plus warfarin group(F=7.852,P=0.007).The intra-group comparisons versus baseline showed that the liver function improved from POD 21 to POM 1,and coagulation function improved from POM 2 in rivaroxaban group.In contrast,the liver function improved from POM 1 to POM 2,and coagulation function improved from POM 4 in LMWH plus warfarin group.The two groups did not significantly differ in liver function decompensation,incidence of liver cancer,or active bleeding(all P>0.05).Conclusion The prophylactic use of rivaroxaban significantly decreases the incidence of PVST after splenectomy and pericardial devascularization in cirrhotic patients compared to LMWH plus warfarin treatment.Besides,rivaroxaban treatment is safe and effective and is associated with improved liver and coagulation functions than LMWH plus warfarin treatment.