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Evaluating the Use of Anticoagulants in Patients with Advanced Liver Disease

Historically, patients with liver cirrhosis have been thought to be “auto-anticoagulated,” naturally protected against venous thrombotic disease. This concept has since been debunked and replaced with the understanding that advanced fibrosis promotes anti-coagulant and pro-thrombotic states.1 Specifically, liver cirrhosis leads to decreased synthesis of the majority of clotting factors, thereby increasing the risk of bleeding in patients with advanced liver disease. However, patients with fibrosis have decreased levels of anticoagulation factors, such as protein C and antithrombin, which promote a pro-thrombotic state. This seemingly contradictory phenomenon places patients with cirrhosis and healthcare providers in a challenging position: should physicians administer prophylactic anticoagulant drugs to patients with cirrhosis? On the one hand, the risk of bleeding increases with the use of anticoagulant drugs; however, without these drugs, patients could be at risk for developing venous thrombotic disease.
In an article in press for publication in Journal of Hepatology, Mark Thursz, MD, professor of hepatology from Imperial College in London, and colleagues, attempt to address this difficult question.2 They introduce the issue of prophylactic anticoagulation by presenting a case study of a man in his late 50s who suffers from chronic hepatitis C with liver cirrhosis. After multiple hospital visits, the patient was admitted to the emergency department complaining of painful swelling in his left leg, which testing later revealed to be a blood clot in his left femoral vein. During previous hospital admissions, physicians opted not to administer prophylactic anticoagulant drugs due to concerns about bleeding. Sadly, the patient suffered a heart attack and died. The cause of death: pulmonary embolism. Dr. Thursz and his colleagues argue that the reasons cited by the physicians against prophylaxis did not make a strong enough case and that the patient could have benefited from anticoagulant drug therapy. They use this case study to pose a series of questions that seek to address the risk of development of thrombosis in patients who suffer from chronic liver disease and whether or not prophylactic anticoagulant drugs should be administered to them.
Before determining if anticoagulant drugs should be administered, it is imperative to assess if there is a real need for such measures in patients with cirrhosis. To examine the correlation between cirrhosis and thrombotic disease, Dr. Thursz and his colleagues cite a Danish study comprising 100,000 patients diagnosed with venous thromboembolism. In this study, patients with liver cirrhosis were shown to be 1.7 times more likely to develop thrombosis compared with the general public. The authors also discussed the risk of developing portal vein thrombosis (PVT), but concluded that in those with chronic liver disease, the magnitude of the risk of developing PVT is unclear.