Cited by 54Blood properties and coagulationThyroid Disorders and TreatmentsBlood Coagulation and Thrombosis Mechanisms

Thyroid Dysfunction and Fibrin Network Structure: A Mechanism for Increased Thrombotic Risk in Hyperthyroid Individuals

Hooper, J. M. W., Stuijver, D. J. F., Orme, S. M., van Zaane, B., Hess, K., Gerdes, V. E., Phoenix, F., Rice, P. +4 more·2012·The Journal of Clinical Endocrinology & Metabolism

Abstract

CONTEXT: Hyperthyroidism is associated with increased thrombosis risk, and fibrin clot structure determines susceptibility to vascular thrombotic events. OBJECTIVE: Our objective was to investigate clot formation and lysis in hyperthyroidism using observational and interventional studies. DESIGN: Ex vivo fibrin clot structure/fibrinolysis and plasma levels of thrombotic/inflammatory markers were investigated in hyperthyroid individuals (n = 24) and matched controls (n = 19), using turbidimetric assays, ELISA, and confocal and electron microscopy. The effects of normalizing thyroid function were analyzed (n = 19) and the role of short-term exogenous hyperthyroidism in healthy volunteers studied (n = 16). RESULTS: Hyperthyroid subjects displayed higher clot maximum absorbance compared with controls (0.41 ± 0.03 and 0.27 ± 0.01 arbitrary units, respectively; P < 0.01), and longer clot lysis time (518 ± 23 and 461 ± 18 sec, respectively; P < 0.05), which correlated with free T(4) levels. Plasma levels of fibrinogen and plasminogen activator inhibitor-1 were significantly higher in patients compared with controls. Normalizing thyroid function in 19 subjects was associated with lower maximum absorbance and shorter lysis time, accompanied by reduction in fibrinogen, plasminogen activator inhibitor-1, and D-dimer levels. Complement C3, but not C-reactive protein, levels were higher in hyperthyroid subjects compared with controls (0.92 ± 0.05 and 0.64 ± 0.03 g/liter, respectively; P < 0.01), correlated with clot structure parameters, and decreased after intervention. Confocal and electron microscopy confirmed more compact clots and impaired fibrinolysis during hyperthyroidism. Exogenous hyperthyroidism in healthy volunteers had no effect on any of the clot structure parameters. CONCLUSIONS: Endogenous hyperthyroidism is associated with more compact clots and resistance to fibrinolysis ex vivo, related to the degree of hyperthyroidism and C3 plasma levels, and these changes are modulated by achieving euthyroidism. Altered clot structure/lysis may be one mechanism for increased thrombotic risk in hyperthyroidism.

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Crossref · 10.1210/jc.2011-2894

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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 [120]

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Authors
Hooper, J. M. W., Stuijver, D. J. F., Orme, S. M., van Zaane, B., Hess, K., Gerdes, V. E., Phoenix, F., Rice, P., Smith, K. A., Alzahrani, S. H., Standeven, K. F., & Ajjan, R. A.
Affiliations
  • University of Leeds (GB)
  • Slotervaartziekenhuis (NL)
  • Leeds Teaching Hospitals NHS Trust (GB)
  • Universitätsklinikum Aachen (DE)
Corresponding author
Ajjan, R. A.
Venue
The Journal of Clinical Endocrinology & Metabolism
Published
2012-05
Volume
97
Issue
5
Pages
1463-1473
ISSN
  • 0021-972X (ISSN-L)
  • 1945-7197
OpenAlex
W1964705259
Cited by
54
References
42
Citations by year
2026: 1 · 2024: 1 · 2023: 3 · 2022: 4 · 2021: 5 · 2020: 4 · 2019: 5 · 2018: 6 · 2017: 4 · 2016: 2 · 2015: 7 · 2014: 3 · 2013: 6 · 2012: 3
FWCI
4.90
Type
journal article
Language
en
Open access
closed
Locations
  • The Journal of Clinical Endocrinology & Metabolism (publishedVersion)
  • PubMed (publishedVersion)
  • Data Archiving and Networked Services (DANS) (submittedVersion)
  • RWTH Publications (RWTH Aachen) (submittedVersion)
  • Pure Amsterdam UMC (submittedVersion)
Funders
British Thyroid Foundation
Topics
  • Health Sciences › Medicine › Pulmonary and Respiratory Medicine › Blood properties and coagulation
  • Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Thyroid Disorders and Treatments
  • Health Sciences › Medicine › Hematology › Blood Coagulation and Thrombosis Mechanisms
Keywords
thrombosis risk, fibrin clot structure, fibrinolysis, clot lysis time, fibrinogen, plasminogen activator inhibitor-1, D-dimer, complement C3, thyroid function normalization, free thyroxine
MeSH terms
Adult, Blood Coagulation, Cross-Sectional Studies, Female, Fibrin, Fibrin Fibrinogen Degradation Products, Fibrinogen, Humans, Hyperthyroidism, Male, Risk, Thrombosis, Thyroid Function Tests, Thyroid Gland, Plasminogen Activator Inhibitor 1

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