Heparins Have Adequate Ex Vivo Anticoagulant Effects In Hospitalized Patients With Cirrhosis

Background Patients with cirrhosis are at risk of venous thromboembolism (VTE), but strategies for thromboprophylaxis have not been defined. Previous in vitro studies suggest an altered anticoagulant effect of heparins in patients with cirrhosis.Objectives To assess the anticoagulant effects of prophylactic low-molecular-weight heparin (LMWH) or unfractionated heparin (UFH) doses in patients with cirrhosis in a real-life clinical setting.Methods We studied patients with cirrhosis (n = 16) and acute-on-chronic liver failure (ACLF) (n = 14), and compared these with patients without underlying liver disease admitted to non-liver general medical wards (n = 18) and non-liver intensive care units (n = 14), respectively. Blood samples were taken before and 4 h after administration of the first dose of LMWH or UFH. We assessed hemostatic status using thrombin generation assays, thrombin-antithrombin complexes (TAT), and conventional coagulation assays, and included healthy controls (n = 20) to establish reference values. Anti-Xa activity was determined to estimate peak heparin levels.Results Baseline thrombin generation was similar among all cohorts and healthy controls despite alterations in conventional coagulation assays. On heparin, both absolute and proportional changes of thrombin generation were comparable between all four cohorts (-62% to -85%). TAT levels decreased in all cohorts apart from the ACLF cohort, but did not correlate with the proportional change in thrombin generation. Anti-Xa activity correlated with the proportional change in thrombin generation in patients receiving LMWH, but not in patients receiving UFH.Conclusions These data suggest that current prophylactic heparin doses have comparable anticoagulant effects in patients with cirrhosis compared with patients without underlying liver disease.