Anticoagulation therapy early is safe in portal vein thrombosis patients with acute variceal bleeding: a multi-centric randomized controlled trial.

Portal vein thrombosis (PVT) and acute variceal bleeding (AVB) are frequent complications of cirrhosis. The efficacy, safety, and timing of anticoagulant treatment in cirrhotic patients with PVT and AVB are contentious issues. We aimed to establish the safety and efficacy of initiating nadroparin calcium-warfarin sequential (NWS) anticoagulation therapy early after esophageal variceal band ligation within PVT patients having cirrhosis and AVB. Cirrhotic patients having AVB and PVT who underwent EVL were included and randomly allocated to either the NWS therapy group (1-month nadroparin calcium by subcutaneous injection following 5-month warfarin through oral administration, n = 43) or the control group (without any anticoagulation therapy, n = 43). The primary endpoint was the rate of PVT recanalization. Secondary endpoints included major bleeding events mainly referring to variceal rebleeding (5-day failure, 14-day, 4-week, 6-week, and 6-month rebleeding rates) and mortality after EVL. The overall recanalization (complete and partial) rate in the NWS therapy group was significantly higher than that in the control group (67.4% vs. 39.5%, P = 0.009). Low Child-Pugh score (P = 0.039, OR: 0.692, 95% CI 0.488-0.982), D-dimer < 2.00 ug/mL (P = 0.030, OR: 3.600, 95% CI 1.134-11.430), and NWS anticoagulation therapy (P = 0.002, OR: 4.189, 95% CI 1.660-10.568) were the predictors of PVT recanalization through univariate analysis of binary logistic regression. NWS anticoagulation therapy (P = 0.003, OR: 4.506, 95% CI 1.687-12.037) was the independent factor of recanalization through multivariate analysis. Nobody bled except for variceal rebleeding. Five-day failure and 14-day rebleeding were zero. There were no significantly different in 4-week (2.3% vs. 4.7%, P = 1.000), 6-week (4.7% vs. 9.3%, P = 0.672) and 6-month rebleeding (18.6% vs. 20.9%, P = 0.787) between the two groups. There was no mortality during six months follow-up. Low serum albumin (P = 0.011, OR: 0.844, 95% CI 0.741-0.962), high MELD score (P = 0.003, OR: 1.564, 95% CI 1.167-2.097) and Child-Pugh score (P = 0.006, OR: 1.950, 95% CI 1.206-3.155) were predictors of rebleeding by univariate analysis of binary logistic regression analysis. The Child-Pugh score (7 [6-8] vs. 6 [5-7], P = 0.003) and albumin levels (33.93 ± 5.30 vs. 37.28 ± 4.32, P = 0.002) were improved in the NWS therapy group at six months. In PVT patients with cirrhosis and AVB, starting NWS anticoagulation therapy early after EVL was safe and effective. It has the potential to raise albumin levels and improve liver function.