Heparin Response and Clearance in Acute and Chronic Liver Disease

Summary Patients with liver disease are at risk of bleeding due to abnormalities of the clotting system although they must be anticoagulated if they require haemodialysis or haemoperfusion. The anticoagulant of choice is heparin. In this study we have investigated heparin kinetics in patients with fulminant hepatic failure (FHF) after a single intravenous dose of heparin (2,500 units) and found there was an increased clearance of heparin whether measured by its anti-Xa effect (t1/2 = 27.8 ± 2.9 min compared to t1/2 = 50.2 ± 2.7 min in normal controls p <0.001) or by the whole blood activated clotting time (t1/2 = 23.7 ± 2.2 min compared to t1/2 = 37.0 ± 2.0 min p <0.001). There was a decreased peak level of heparin measured by anti-Xa effect (peak level in FHF = 0.48 ± 0.05 u/ml and in controls = 0.69 ± 0.04 u/ml, p <0.02), but an increased sensitivity to heparin (sensitivity in FHF = 0.072 ± 0.011 sec/unit, in controls 0.033 ± 0.003 sec/unit, p <0.001). Patients with FHF had very low levels of antithrombin III (AT III), but there was no correlation between this and any parameters of heparin effect or clearance. In a group of patients with chronic liver disease heparin kinetics did not differ from controls despite low levels of AT III. The changes in heparin kinetics in FHF are likely to be complex with the balance between the proteins that act as cofactors, (e.g. AT III) and the proteins that have heparin neutralising activity, controlling the response of added heparin.