Alterations in coagulation and fibrinolysis after levothyroxine exposure in healthy volunteers: a controlled randomized crossover study

J Thromb Haemost. 2011 Sep;9(9):1816-24. doi: 10.1111/j.1538-7836.2011.04430.x.

Abstract

Background: Several hemostatic abnormalities have been reported in hyperthyroidism, but the overall effect of thyroid hormone excess on coagulation and fibrinolysis is unclear.

Objective: Our aim was to assess whether the use of supraphysiological doses of levothyroxine leads to coagulation activation and inhibition of fibrinolysis.

Patients and methods: Healthy volunteers were randomized to receive levothyroxine or no medication for 14 days with a washout period of at least 28 days in a crossover design. To study the effects of different degrees of thyroid hormone excess, 16 participants received levothyroxine in a dose of 0.3 mg per day, and 12 received levothyroxine 0.45 or 0.6 mg per day depending on body weight. Several variables of coagulation and fibrinolysis were measured.

Results: Levels of von Willebrand factor activity (VWF:RiCo) and antigen (VWF:Ag), factor (F) VIII, plasminogen activator inhibitor-1 (PAI-1) and clot-lysis time were slightly higher after levothyroxine 0.3 mg per day than after the control situation, but only levels of VWF showed a significant increase from baseline. After levothyroxine 0.45 or 0.6 mg per day, levels of fibrinogen increased by 17%, VWF activity by 24%, VWF antigen by 26%, FVIII by 19%, FIX by 14%, FX by 7%, PAI-1 by 116% and clot-lysis time by 14%, and activated partial thromboplastin time decreased by 3%; all were significant changes compared with the control situation. We did not observe clear evidence of coagulation activation.

Conclusions: Our data suggest that thyroid hormone excess increases coagulation factor levels and inhibits fibrinolysis in a dose-dependent fashion. This implies an increased risk of venous thrombosis during hyperthyroidism.

Publication types

  • Clinical Trial
  • Randomized Controlled Trial

MeSH terms

  • Adult
  • Blood Coagulation / drug effects*
  • Blood Coagulation Factors / metabolism
  • Cross-Over Studies
  • Female
  • Fibrinolysis / drug effects*
  • Humans
  • Hyperthyroidism / blood
  • Hyperthyroidism / complications
  • Male
  • Risk Factors
  • Thyroid Hormones / blood
  • Thyroxine / administration & dosage
  • Thyroxine / adverse effects*
  • Venous Thrombosis / blood
  • Venous Thrombosis / etiology

Substances

  • Blood Coagulation Factors
  • Thyroid Hormones
  • Thyroxine