LAUSR

Direct oral anticoagulants (DOACs) are increasingly used for the treatment and prevention of venous thromboembolism (VTE), including in patients with liver disease. Dabigatran, a factor IIa inhibitor, is approved for treatment of VTE and to reduce the risk of stroke and systemic embolism in patients with non-valvular atrial fibrillation. Furthermore, there is an approved and available direct reversal agent, idarucizumab. Reversal agents for other DOACs (factor Xa inhibitors) are under evaluation, but not currently available for clinical use. Patients with cirrhosis are universally excluded from clinical trials in DOAC, but knowledge of the efficacy and safety is growing in this population. The risk of portal vein thrombosis (PVT) and VTE in cirrhosis is increasingly recognized, and treatment often presents a difficult clinical dilemma. Current expert recommendations support the use of anticoagulation for treatment of PVT in patients listed for liver transplantation without contraindication. We present a case of a 60-year-old man with cirrhosis from primary sclerosing cholangitis and hepatocellular carcinoma (HCC) treated with dabigatran 150mg twice daily (anti-factor IIa) for recurrent lower extremity deep venous thrombosis (DVT) while listed for liver transplant. Prior hepatic decompensation in the past included esophageal variceal bleeding, hepatic encephalopathy, and ascites. At the time of transplant, he had aModel for End-Stage Liver Disease (MELD) score of 12 (HCC exception 29) and was Child-Turcotte-Pugh class B. The patient’s total bilirubin was 1.7 mg/dL, creatinine 1.0 mg/dL and INR 1.4. The patient was initially treated with apixaban 5mg twice daily (anti-factor Xa) for 3 months after discovery of a recurrent VTE while on warfarin. There were no bleeding events while treated with apixaban or dabigatran. Due to a further increase inMELD score and imminent transplant, the patient was transitioned to dabigatran because of the availability of an approved direct reversal agent: idarucizumab. Dabigatran was selected, rather than enoxaparin, specifically due to the ease of use for the patient and the availability of a direct reversal agent. The patient was treated with dabigatran for 44 days until a suitable organ became available. Liver transplant with a split-liver graft (right lobe) was successfully performed after preoperative administration of 5g of intravenous idarucizumab. Prior to reversal of dabigatran, the thrombin time (TT) was 56.6 seconds (s) (normal range 9.0 18.0 s), the prothrombin time (PT) was 16.2 s (normal range 9.8-12.6 s), and the activated partial thromboplastin time (aPTT) was 35.8 s (normal range 27.8-37.6 s). The patient did not experience significant blood loss during the operation, and no intraoperative blood transfusion was required. On postoperative day 3, the patient developed a bile leak and was taken back to the operating room for repair. The patient was started on aspirin and subcutaneous unfractionated heparin prophylaxis on post-operative day 6 and restarted oral dabigatran on postoperative day 10. To date, the patient’s lower extremity DVT persists and due to a history of multiple DVT the patient will require indefinite anticoagulation. To our knowledge, this is the first case reported of the successful use of idarucizumab to reverse the Abbreviations: aPTT, activated partial thromboplastin time; DOAC, direct oral anticoagulant; DVT, deep venous thrombosis; HCC, hepatocellular carcinoma; MELD, Model for End-Stage Liver Disease; PT, prothrombin time; PVT, portal vein thrombosis; s, seconds; TT, thrombin time; VTE, venous thromboembolism.