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