Mechanism of the heparin-induced increase in the concentration of free thyroxine in plasma.

The iv administration of heparin causes an increase in the plasma free T4 concentration, as determined by equilibrium dialysis. The mechanism and physiological consequences of this action of heparin are unknown. To explore the possibility that the heparin-induced increase in plasma free T4 is an in vitro artifact due to generation of FFA during equilibrium dialysis, we studied plasma samples from 10 subjects treated with iv heparin. In plasma from 4 of these subjects, free T4 concentrations measured by equilibrium dialysis did not increase above baseline values after heparin administration. In incubations performed in parallel with the equilibrium dialysis measurements, FFA concentrations in these plasma samples were found to increase, but in no subject did they exceed 2.5 meq/L after incubation. In contrast, in plasma from the other 6 subjects treated with heparin, free T4 concentrations rose markedly (by 130-520%) above baseline values after heparin administration. In all of these postheparin plasma samples, FFA concentrations were less than 2.8 meq/L before incubation, but rose during incubation by 80-270% to more than 3.8 meq/L. Treatment of these plasma samples with protamine to inhibit lipoprotein lipase and with specific antiserum to inhibit hepatic triglyceride lipase before equilibrium dialysis or incubation prevented, in parallel, the heparin-induced increases in FFA and free T4 concentrations. From these findings we conclude that the heparin-induced increase in free T4 is usually an in vitro artifact, and that most subjects receiving heparin have a normal plasma free T4 concentration in vivo. We also conclude that this in vitro artifact may account for many of the findings that led to the postulate of an inhibitor of T4 binding to plasma and intracellular proteins in heparin-treated patients and perhaps in patients with nonthyroid illness as well.