Heparin
TFTs performed in individuals receiving heparin, can demonstrate fallaciously elevated FT4 and FT3, with normal TSH levels.14,15
Mechanism of interference: Heparin induces release of lipoprotein lipase (LPL) from vascular endothelium, which acts on triglycerides, results in an increase in serum levels of non-esterified fatty acids (NEFA). High NEFA levels inhibit binding of thyroid hormone with TBP, producing an increase in the measured free hormone levels.14 There is a demonstrable increase in blood levels of LPL as well as FFA, that persists in-vitro, in patients receiving heparin.14,15
Relation to the type of heparin: This effect has been reported with the use of unfractionated heparin (UFH) as well as low molecular weight heparin (LMWH), irrespective of the route or dose. Standard subcutaneous doses, as well as intravenous doses as small as 0.08U/kg, can cause a significant increase in LPL activity of the serum.16 It takes ten hours or more after UFH injection for this effect to remit.17 Greater bioavailability and longer duration of action of LMWH might necessitate an interval of 24 hrs after the last dose for this effect to wane.
Variations depending on assay and storage: This interference has been observed with different assays, including direct immunoassays, ultracentrifugation, and equilibrium dialysis.18Assays that require longer incubation periods (e.g. equilibrium dialysis) show maximum derangement. As an extension of the same effect, preanalytical delays due to storage of samples before testing can also worsen this interference as in-vitro displacement of FT4 and FT3 continues.14
Physiologic variations: These TFT abnormalities are not seen in all patients receiving heparin as there are other factors at play, namely serum levels of triglycerides and albumin. The released LPL requires an adequate concentration of the substrate i.e. triglycerides (>180 mg/dl) in the serum to cause an increase in FFA. Albumin acts as a high-affinity binding protein for FFA; thus its serum concentration affects the FFA-induced effects on thyroid hormone displacement. FT4 levels remain unaltered, till such time that the molar concentration of FFA is five times more than that of albumin, overwhelming its binding capacity.19
Clinical correlate: Collecting blood samples after an adequate gap (at least 10 hours with UFH), immediate processing and testing and correlation with TSH can mitigate the problem. Estimating TT4 instead of FT4 in individuals receiving heparin specially in those having hypertriglyceridemia can be helpful.20
Drugs affecting thyroxine-binding globulin