Heparin-Induced Thrombotic Thrombocytopenia in Budd-Chiari Syndrome: Anticoagulation of Choice?

Abstract

Budd Chiari Syndrome (BCS) is characterized by hepatic venous outflow tract obstruction leading to post sinusoidal portal hypertension. If untreated, BCS is often fatal. Guidelines recommend heparin and its derivatives for anticoagulation (AC) in BCS. A 23 year-old Caucasian female with no medical history presented with a ten day history of abdominal pain and worsening distension. She reported occasional alcohol use and a remote history of oral contraceptive use 2 years back. She denied a personal and family history of liver disease and hypercoagulable disorders. Laboratory tests showed Hgb of 16.7 gm/dl, WBC of 18.9K, platelet of 525K, AST of 733 U/L, ALT of 889 U/L, AP of 162 U/L, total bilirubin of 3.6 mg/dl, and INR of 1.42. Doppler ultrasound (US) of the liver showed occlusion of the hepatic veins, hepato-splenomegaly and ascites. Contrast-enhanced computed tomography (CECT) confirmed these findings and showed patent but dilated (1.4 cm) portal vasculature and collaterals suggestive of portal hypertension. She was started on intravenous heparin and underwent Transjugular Intrahepatic Portosystemic Shunt (TIPS) placement with a final gradient of 5mmHg. Her liver enzymes initially improved, but began to worsen 8 days later. She developed marked thrombocytopenia and abdominal ecchymosis with eschar (Figure 1). A repeat US Doppler showed decreased flow within TIPS (Figure 2) and new portal vein thrombosis. Positive immunoassay for heparin antibodies confirmed Heparin Induced Thrombotic Thrombocytopenia (HITT). Anticoagulation was changed to bivalirudin and she underwent TIPS revision with thrombectomy. Hypercoagulable work up revealed JAK2-V617F mutation suggestive of myeloproliferative processes- Polycythemia Vera (PCV) and Essential Thrombocythemia (ET). The incidence of BCS is 0.2-0.8 per million/year, however the mortality in untreated BCS is 80-90%. Most BCS cases are acquired and up to 84% of cases have thrombotic diathesis, the most common being PCV and/or ET. Aside from TIPS and liver transplantation, initial AC with heparin is the standard of care. The overall prevalence of HITT from all use is low at 0.2-5.2%. However, in a retrospective study, 9/32 (28%) patients with BCS developed HITT. Our patient initially responded to heparin, but later had extension of thrombosis. This raises the question of alternative anticoagulation such as Direct Thrombin inhibitors in this patient population.Figure: Abdominal eschar due to HITT.Figure: Clotted TIPS - pre and post IR revision.Figure: US doppler showing clotted TIPS.