Effect of heparin on serum free thyroxine linked to post-heparin lipolytic activity

A possible association between free T4 (fT4) changes, occurring after heparin administration, and the post-heparin lipolytic activity, i.e., the release of lipases and the lipolysis of triglycerides to non-esterified fatty acids (NEFAs) was studied. In 19 patients heparin increased mean fT4 values obtained by equilibrium dialysis from 23.4 to 38.6 pmol/l (P less than 0.01) and mean fT4 values measured by GammaCoat two-step RIA from 17.0 to 24.1 pmol/l (P less than 0.01), the results of the two methods agreeing well (rs = 0.88). Concurrently, NEFAs increased from a mean of 0.55 to 2.20 mmol/l (P less than 0.01) and fT4 increases were significantly correlated with post-heparin NEFAs (rs = 0.69, P less than 0.001). In vitro addition of palmitic acid to sera increased fT4 concentrations to values similar to those observed in vivo. Post-heparin fT4 increases were also strongly correlated to the concentrations of triglycerides (rs = 0.63, P less than 0.01). Hypertriglyceridaemia was associated with pronounced fT4 increases after heparin administration, and normolipidaemia with moderate or no changes. These results suggest that the effect of heparin on fT4 is linked to the activation of lipases by heparin and is mediated by NEFAs, which, at high concentrations, compete with thyroxine for binding proteins.