Anticoagulants in Liver Disease

Anticoagulation in liver disease is the use of antithrombotic drugs for venous thromboembolism, portal vein thrombosis and atrial fibrillation in patients with rebalanced haemostasis. Reduced synthesis of procoagulant factors is balanced by reduced natural anticoagulants and raised factor VIII and von Willebrand factor, so a raised INR does not protect against thrombosis.

INR limits. INR measures only procoagulant factors and overstates bleeding risk. It is unreliable for monitoring warfarin when baseline INR is already raised.

Anti-Xa limits. Low antithrombin causes anti-Xa activity to underestimate heparin effect.

Bleeding risk. Bleeding in cirrhosis is driven mainly by portal hypertension, not coagulation tests. Screen for and treat varices before or during anticoagulation.

Venous thromboembolism prophylaxis. Give low molecular weight heparin to hospitalised cirrhotic patients with usual risk factors, unless platelets are under 50 × 10^9/L or bleeding is active.

Portal vein thrombosis. Anticoagulate recent thrombosis, thrombosis extending to the mesenteric veins, and thrombosis in transplant candidates.

Agent choice by Child-Pugh class.

Antiplatelets. Aspirin and clopidogrel raise bleeding risk; use only with clear cardiovascular indication.

Enoxaparin. - Prophylaxis: 40 mg subcutaneously once daily; 20 mg once daily if creatinine clearance is under 30 mL/min. - Treatment: 1 mg/kg subcutaneously every 12 hours, using dry weight; 1 mg/kg once daily if creatinine clearance is under 30 mL/min.

Apixaban. Venous thromboembolism treatment 10 mg orally twice daily for 7 days, then 5 mg twice daily. Atrial fibrillation 5 mg twice daily; 2.5 mg twice daily if 2 of age 80 years or more, weight 60 kg or less, creatinine 133 micromol/L or more.

Rivaroxaban. Child-Pugh A only: 15 mg orally twice daily with food for 21 days, then 20 mg once daily for venous thromboembolism.

Duration for portal vein thrombosis. At least 6 months. Continue long term in transplant candidates, mesenteric extension or recurrent thrombosis.

Reversal. - Unfractionated or low molecular weight heparin: protamine, dose by agent and timing. - Dabigatran: idarucizumab 5 g intravenously. - Apixaban and rivaroxaban: andexanet alfa where available, or four-factor prothrombin complex concentrate 50 units/kg. - Fresh frozen plasma corrects INR poorly and expands volume; avoid giving it to correct INR before procedures.

Special groups. - Kidney impairment: hepatorenal physiology increases low molecular weight heparin and dabigatran accumulation. - Pregnancy: low molecular weight heparin is the anticoagulant of choice; direct oral anticoagulants and warfarin are avoided. - Breastfeeding: low molecular weight heparin and warfarin are compatible; direct oral anticoagulants are not advised. - Older adults: dose apixaban by its reduction criteria.

Baseline. Platelet count, INR, fibrinogen, creatinine, haemoglobin and endoscopic variceal status.

Monitoring. Platelet count and haemoglobin weekly at first, then monthly. Imaging at 3 and 6 months for portal vein thrombosis recanalisation. Anti-Xa levels only in extremes of weight or kidney impairment, interpreted with caution.

Stopping. Stop for major bleeding, platelets under 30 × 10^9/L, or progression to Child-Pugh C on a direct oral anticoagulant.

Referral and escalation. Discuss with hepatology and haematology before anticoagulating Child-Pugh C patients, platelet counts under 50 × 10^9/L, or patients with unbanded large varices.