| BackgroundPortal vein thrombosis(PVT)is a frequent complication of cirrhosis,which can lead to complication of portal hypertension such as esophageal and gastric varicose vein hemorrhage,ascites or even death.Therapy includes anticoagulation,thrombolysis and transjugular intrahepatic portosystemic shunt(TIPS).Early initiation of anticoagulation can result in partial or complete recanalization of portal vein in which thrombosis formed.Currently,anticoagulant therapy of PVT patients with cirrhosis remains controversial because coagulation function of cirrhotic patients was impaired.A limited number of published studies reported that anticoagulants such as low molecular weight heparin(LMWH)and warfarin were effective for cirrhotic patients with PVT,however,most of them were retrospective observational studies.The efficacy and safety of LMWH and warfarin in PVT patients with cirrhosis remains a matter of debate,on which there are few prospective randomized controlled studies.In addition,anticoagulant drugs have been used alone in PVT patients in most of published studies(LMWH alone or warfarin alone).LMWH requiring subcutaneous injection substantially results in a low compliance of patients during a long-term therapy.Simultaneously,warfarin is restricted in patients who are in the fasting state.Therefore,LMWH followed by warfarin may become a better option for cirrhotic patients who has just received endoscopic therapy,which combines advantages of these two kinds of drugs and avoids disadvantages.AimsA prospective randomized controlled trial was conducted to evaluate the recanalization rate and bleeding risks of PVT with nadroparin calcium-warfarin sequential anticoagulant therapy in patients with cirrhosis.The predictors of PVT recanalization and impact of anticoagulation on liver function were also assessed.MethodsCirrhotic inpatients with PVT diagnosed by abdominal enhanced computed tomography(CT),magnetic resonance imaging(MRI)or portal vein angiography,who have not received anticoagulation therapy were consecutively enrolled from January 2017 to July 2019 at Qilu Hospital of Shandong University in China.The patients were randomly allocated to nadroparin calcium-warfarin sequential(NWS)therapy group or control group.Patients in NWS therapy group received 4100IU nadroparin calcium subcutaneously every 12h for 1 month followed by warfarin orally for 5 months.Warfarin was started with an initial dosage of 3.0 mg daily and adjusted by international normal ratio until the INR target of 2-3 was achieved.Patients in the control group received no anticoagulation therapy.Overall recanalization rate of PVT was evaluated by imaging examination at 6th month.Bleeding risk and liver function were also analyzed.Univariate and multivariate Logistic regression analysis were used to analyze the predictors of recanalization of PVT.ResultsA total of 64 patients were randomly assigned to the NWS therapy group and the control group.In the NWS therapy group,thirty patients completed the trial,with one quitting the trial and one lost to follow-up.In the control group,thirty patients completed the trial,with two lost to follow-up.The intentional-to-treat(ITT)analysis showed that overall recanalization rate of NWS therapy group was higher than that of control group(62.5%vs 34.4%,P=0.024).The per-protocol(PP)analysis showed that the overall recanalization rate of NWS therapy group was higher than that of control group(63.3%vs 30.0%,P=0.010),with statistically significant difference.There was no statistically significant difference in the bleeding rates between two groups.Univariate Logistic regression analysis suggested that lower Child-Pugh score,D-dimer<2.00?g/mL and NWS anticoagulation therapy were predictors of PVT recanalization.The level of triglyceride and time interval from diagnosis to initiation of anticoagulation<1 month were predictors of PVT recanalization in patients with anticoagulation.Multivariate Logistic regression analysis suggested that NWS anticoagulation therapy(P=0.008,OR:6.345;95%CI:1.629-24.721)was an independent predictor of PVT recanalization.In NWS therapy group,the Child-Pugh score[7(6-8)vs 6(5-7),P=0.007]and the level of albumin(36.06±5.13 vs 38.64±3.75,P=0.004)were improved at 6th month,with statistically significant difference.ConclusionsNWS therapy was effective and safe for cirrhotic patients with PVT and could improve liver function and level of albumin.NWS anticoagulation therapy,Child-Pugh score and D-dimer were closely related with PVT recanalization.Anticoagulation therapy was independent predictor of PVT recanalization.Lower triglyceride and early initiation of anticoagulation may predict a higher PVT recanalization rate with anticoagulation. |
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