TY - JOUR
T1 - Thyroid Dysfunction and Fibrin Network Structure: A Mechanism for Increased Thrombotic Risk in Hyperthyroid Individuals
AU - Hooper, J. M. W.
AU - Stuijver, D. J. F.
AU - Orme, S. M.
AU - van Zaane, B.
AU - Hess, K.
AU - Gerdes, V. E.
AU - Phoenix, F.
AU - Rice, P.
AU - Smith, K. A.
AU - Alzahrani, S. H.
AU - Standeven, K. F.
AU - Ajjan, R. A.
PY - 2012
Y1 - 2012
N2 - 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. (J Clin Endocrinol Metab 97: 1463-1473, 2012)
AB - 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. (J Clin Endocrinol Metab 97: 1463-1473, 2012)
U2 - https://doi.org/10.1210/jc.2011-2894
DO - https://doi.org/10.1210/jc.2011-2894
M3 - Article
C2 - 22378816
SN - 0021-972X
VL - 97
SP - 1463
EP - 1473
JO - Journal of clinical endocrinology and metabolism
JF - Journal of clinical endocrinology and metabolism
IS - 5
ER -