title: Thyroid dysfunction and fibrin network structure: a mechanism for increased thrombotic risk in hyperthyroid individuals.
abstract: BACKGROUND
  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.
  
  
  METHODS
  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.
authors.affiliation: Division of Cardiovascular and Diabetes Research, Multidisciplinary Cardiovascular Research Centre, University of Leeds, Leeds LS2 9JT, United Kingdom.
authors.forename: J M W
authors.initials: JM
authors.lastname: Hooper
authors.forename: D J F
authors.initials: DJ
authors.lastname: Stuijver
authors.forename: S M
authors.initials: SM
authors.lastname: Orme
authors.forename: B
authors.initials: B
authors.lastname: van Zaane
authors.forename: K
authors.initials: K
authors.lastname: Hess
authors.forename: V E
authors.initials: VE
authors.lastname: Gerdes
authors.forename: F
authors.initials: F
authors.lastname: Phoenix
authors.forename: P
authors.initials: P
authors.lastname: Rice
authors.forename: K A
authors.initials: KA
authors.lastname: Smith
authors.forename: S H
authors.initials: SH
authors.lastname: Alzahrani
authors.forename: K F
authors.initials: KF
authors.lastname: Standeven
authors.forename: R A
authors.initials: RA
authors.lastname: Ajjan
mesh_terms: D000328:Adult; D001777:Blood Coagulation; D003430:Cross-Sectional Studies; D005260:Female; D005337:Fibrin / Q000378:metabolism*; D005338:Fibrin Fibrinogen Degradation Products / Q000378:metabolism; D005340:Fibrinogen / Q000378:metabolism; D006801:Humans; D006980:Hyperthyroidism / Q000097:blood / Q000150:complications* / Q000503:physiopathology; D008297:Male; D017395:Plasminogen Activator Inhibitor 1 / Q000097:blood; D012306:Risk; D013927:Thrombosis / Q000097:blood / Q000209:etiology* / Q000503:physiopathology; D013960:Thyroid Function Tests; D013961:Thyroid Gland / Q000503:physiopathology*
chemical_list: D005338:Fibrin Fibrinogen Degradation Products; D017395:Plasminogen Activator Inhibitor 1; C036309:fibrin fragment D; D005337:Fibrin; D005340:Fibrinogen