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Cited by 46Thyroid Disorders and TreatmentsBlood Coagulation and Thrombosis MechanismsBlood properties and coagulation

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

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VAN ZAANE, B., SQUIZZATO, A., DEBEIJ, J., DEKKERS, O.M., MEIJERS, J.C.M., VAN ZANTEN, A.P., BÜLLER, H.R., GERDES, V.E.A. +2 more·2011·Journal of Thrombosis and Haemostasis
DOI 10.1111/j.1538-7836.2011.04430.x
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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.

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  • Thyrotoxicosis induced by administration of LT4 to healthy volunteers and those with thyroid nodules induces a procoagulant state, associated with increased levels of FVIII, FIX, FX, VWF, fibrinogen D-dimer, and PAI-1 with delayed fibrin clot lysis and a shortening of the APTT, but with an inconsistent impact on clot structure parameters.

    “Thyrotoxicosis induced by administration of LT4 to healthy volunteers and those with thyroid nodules also induces a procoagulant state, associated with increased levels of FVIII, FIX, FX, VWF, fibrinogen D-dimer, and PAI-1 with delayed fibrin clot lysis and a shortening of the APTT, but with an inconsistent impact on clot structure parameters”

    From Pharmacodynamic and Therapeutic Actions of Levothyroxine (2021) · cites this paper as [121]

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Authors
VAN ZAANE, B., SQUIZZATO, A., DEBEIJ, J., DEKKERS, O. M., MEIJERS, J. C. M., VAN ZANTEN, A. P., BÜLLER, H. R., GERDES, V. E. A., CANNEGIETER, S. C., & BRANDJES, D. P. M.
Affiliations
  • University of Insubria (IT)
  • Leiden University Medical Center (NL)
  • Amsterdam UMC Location University of Amsterdam (NL)
  • Slotervaartziekenhuis (NL)
ORCID
Venue
Journal of Thrombosis and Haemostasis
Publisher
Elsevier BV
Published
2011-09
Volume
9
Issue
9
Pages
1816-1824
ISSN
1538-7836 (ISSN-L)
DOI
10.1111/j.1538-7836.2011.04430.x
OpenAlex
W1769349910
Cited by
46
References
40
Citations by year
2026: 1 · 2025: 1 · 2024: 2 · 2023: 2 · 2022: 2 · 2021: 5 · 2020: 2 · 2019: 3 · 2018: 3 · 2017: 7 · 2016: 2 · 2015: 5 · 2014: 5 · 2013: 2 · 2012: 4
FWCI
2.89
Type
journal article
Language
en
Open access
Licence
Locations
  • Journal of Thrombosis and Haemostasis (publishedVersion)
  • PubMed (publishedVersion)
  • Pure Amsterdam UMC (publishedVersion)
  • Data Archiving and Networked Services (DANS) (submittedVersion)
  • Leiden Repository (Leiden University) (submittedVersion)
  • IrInSubria (University of Insubria) (submittedVersion)
Topics
  • Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Thyroid Disorders and Treatments
  • Health Sciences › Medicine › Hematology › Blood Coagulation and Thrombosis Mechanisms
  • Health Sciences › Medicine › Pulmonary and Respiratory Medicine › Blood properties and coagulation
Keywords
levothyroxine, hyperthyroidism, thyroid hormone excess, coagulation, fibrinolysis, von Willebrand factor, factor VIII, plasminogen activator inhibitor-1, fibrinogen, clot lysis time, activated partial thromboplastin time, venous thrombosis risk, dose-dependent effects
MeSH terms
Adult, Blood Coagulation, Blood Coagulation Factors, Female, Fibrinolysis, Humans, Hyperthyroidism, Male, Risk Factors, Thyroid Hormones, Thyroxine, Cross-Over Studies, Venous Thrombosis

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