Cirrhosis,Thrombosis,Finding FaXts about Doses: Dosing of Unfractionated Heparin for Venous Thromboembolism in Cirrhosis

Background: Despite known disease-specific alterations to anti–factor Xa (AXA) levels, the physiological response of patients with cirrhosis to unfractionated heparin (UFH) infusions is not well established in clinical settings. Objective: The purpose of this study was to characterize the dosing and safety profile of UFH in patients with varying degrees of cirrhosis when treated for venous thromboembolism (VTE). Methods: This retrospective observational study was conducted at a single academic medical center in the United States. Patients with a diagnosis of cirrhosis who received UFH infusions for greater than 48 hours for treatment of VTE were included. Comparisons between heparin infusion rates, AXA levels, and safety outcomes based on severity of cirrhosis were made to define differences between those groups. Results: When compared by compensation status or by Child-Turcotte-Pugh (CTP) class, patients with more severe disease trended toward lower initial AXA levels on heparin initiation and higher heparin requirements to achieve therapeutic levels and were significantly less likely to achieve therapeutic levels than patients with less severe disease (P = 0.001 for compensation, P = 0.017 for CTP). Additionally, bleeding rates were higher in patients with more severe disease, without reaching statistical significance. Conclusion and Relevance: Patients with severe cirrhosis required higher doses of heparin to achieve the same therapeutic AXA levels, but also tended to have higher rates of bleeding compared with less severe cirrhosis. These results represent further evidence of changes in heparin response as cirrhosis severity increases and may suggest that current monitoring methods are suboptimal in this patient population.