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.
Keywords
Heparin - Fulminant hepatic failure - Anticoagulation
