Can heparin alter Thyroxine (T4) results?

Heparin's Effect on Thyroxine (T4) Test Results

Yes, heparin can significantly alter T4 test results, particularly causing falsely elevated free T4 values when measured by equilibrium dialysis methods.

Mechanism of Interference

• Heparin releases lipase activity into plasma, which acts on triglycerides in vitro to generate non-esterified fatty acids (NEFAs) 1
• These released fatty acids compete with T4 for binding proteins, leading to artificially increased free T4 measurements 1, 2
• The effect is most pronounced in methods requiring longer incubation times, such as equilibrium dialysis 1

Factors Affecting the Magnitude of Interference

• Triglyceride levels in the sample significantly impact the degree of interference:
  • Samples with triglycerides >180 mg/dL show more pronounced effects 1
  • Hypertriglyceridemia is associated with more dramatic free T4 increases after heparin exposure 2
• Heparin dosage:
  • Even extremely low doses of heparin (as little as 0.08 U/kg or 5.6 U in a 70-kg person) can release enough lipase activity to alter results 1
  • Both intravenous and subcutaneous heparin administration can cause this effect 1, 3
• Timing:
  • Effects can be seen within 15 minutes of intravenous heparin administration 3
  • Changes persist during continuous heparin infusion 4

Different Assay Methods Show Different Effects

• Equilibrium dialysis methods consistently show increased free T4 values after heparin exposure 1, 3, 5
• Different radioimmunoassay methods respond differently to heparin:
  • Some RIA methods show increased free T4 values similar to equilibrium dialysis 3
  • Other RIA methods may actually show decreased free T4 values after heparin 3
• The correlation between different measurement methods may be poor in heparin-treated patients 3

Clinical Implications

• The heparin-induced increase in free T4 is primarily an in vitro artifact and does not reflect true thyroid status 5
• Most patients receiving heparin actually have normal free T4 concentrations in vivo despite abnormal test results 5
• This artifact may lead to misdiagnosis of thyroid disorders in hospitalized patients receiving heparin 1
• The effect can be prevented by:
  • Using protamine to inhibit lipoprotein lipase activity in the sample 1, 5
  • Using antibodies against hepatic triglyceride lipase 1, 5
  • Choosing alternative assay methods less susceptible to this interference 1

Recommendations for Clinical Practice

• When possible, collect blood samples at least 4 hours after cessation of unfractionated heparin infusion and ≥12 hours after a dose of low molecular weight heparin 6
• Consider using alternative thyroid function tests in patients receiving heparin therapy 1
• Be cautious when interpreting elevated free T4 results in patients receiving any form of heparin, including low-dose heparin flushes 1
• In hospitalized patients receiving heparin, equilibrium dialysis may not be the optimal method for assessing free T4 concentrations 1