The anti-clotting agent enoxaparin prevents portal vein thrombosis (PVT) in patients with cirrhosis, according to the November issue of Gastroenterology.
PVT can lead to portal hypertension and reduce the blood supply to the liver—some patients with acute or extensive PVT develop severe gastrointestinal bleeding, ascites, or intestinal ischemia, which can progress and become fatal. PVT occurs frequently in patients with cirrhosis, with an incidence as high as 40% in patients with advanced disease. It might be caused by cirrhosis-associated changes in the liver cytoarchitecture, such as periportal lymphangitis and fibrosis, altered production of inhibitors of coagulation, or changes in numbers of platelet levels.
Anticoagulants can reverse acute PVT in subjects without liver disease, and low-molecular-weight heparin and vitamin K antagonists have been reported to induce recanalization in patients with liver disease.
Erica Villa et al. investigated whether enoxaparin, a low molecular-weight heparin and anticoagulant used to prevent and treat deep-vein thrombosis or pulmonary embolism, could prevent PVT in patients with advanced cirrhosis (Child–Pugh classes B7–C10).
Thirty-four patients with patent portal veins and no hepatocellular carcinoma were given enoxaparin (4000 IU/day, subcutaneously for 48 weeks), whereas 36 received no treatment (controls). The patients were then evaluated by ultrasonography every 3 months and computed tomography every 6 months.
Villa et al. found that anticoagulant treatment with enoxaparin significantly reduced development of PVT and liver decompensation, and markedly improved liver function and reduced Child–Pugh scores.
“At the end of the follow-up period, 8.8% of patients in the enoxaparin group and 27.7% of controls developed PVT,” explained Villa in a video abstract (click below):
By the end of the study, 8 patients in the enoxaparin group and 13 controls had died. No relevant side effects or hemorrhagic events were reported.
Villa et al. found that enoxaparin caused definite improvements in liver function and reduced occurrence or recurrence of decompensation (mostly ascites), so the drug might have effects beyond simply preventing thrombosis. They proposed that enoxaparin could increase intestinal microcirculation, to reduce enterocytic damage and bacterial translocation.
In an editorial that accompanies the article, Robert J. Fontana pointed out that the incidence of documented bacterial infections was significantly lower in patients that received enoxaparin than controls, and that levels of intestinal fatty acid binding proteins (a marker of enterocyte damage) decreased significantly only in the treated group. Similarly, 3 markers of microbial translocation, including serum levels of bacterial DNA, were lower during enoxaparin therapy, whereas they did not change in controls.
Fontana says that these observations indicate that low molecular-weight heparins could have anti-inflammatory effects and improve intestinal microcirculation.
Read the article online. This article has accompanying CME activities.
Villa E, Cammà C, Marietta M, et al. Enoxaparin prevents portal vein thrombosis and liver decompensation in patients with advanced cirrhosis. Gastroenterology 2012;143:1253−1260.e4.
Read the accompanying editorial.
Fontana RJ. Prophylactic anticoagulation in cirrhotics: a paradox for prime time? Gastroenterology 2012;143:1138-1141.