Manuscript handled by: M. Cushman
High levels of procoagulant factors mediate the association between free thyroxine and the risk of venous thrombosis: the MEGA study
Article first published online: 10 JUN 2014
© 2014 International Society on Thrombosis and Haemostasis
Journal of Thrombosis and Haemostasis
Volume 12, Issue 6, pages 839–846, June 2014
How to Cite
High levels of procoagulant factors mediate the association between free thyroxine and the risk of venous thrombosis: the MEGA study. J Thromb Haemost 2014; 12: 839–46., , , , , , , , , , .
Final decision: M. Cushman, 13 March 2014
- Issue published online: 10 JUN 2014
- Article first published online: 10 JUN 2014
- Accepted manuscript online: 28 MAR 2014 06:07AM EST
- Manuscript Accepted: 13 MAR 2014
- Manuscript Received: 22 JUL 2013
- The Netherlands Heart Foundation. Grant Number: 98.113
- Dutch Cancer Foundation. Grant Number: RUL 99/1992
- Netherlands Organization for Scientific Research. Grant Number: 912-03-033|2003
- coagulation factors;
- thyroid-stimulating hormone;
Thyroid hormone affects the coagulation system, but its effect on clinical disease is not clear. We determined the associations of levels of free thyroxine (FT4), thyroid-stimulating hormone (TSH) and anti-thyroid peroxidase antibodies (antiTPO) with levels of coagulation factors and the risk of venous thrombosis.
In a large population based case–control study (Multiple Environmental and Genetic Assessment of risk factors for venous thrombosis study) on the etiology of venous thrombosis, we determined the levels of FT4, TSH, antiTPO, factor FII, FVII, FVIII, FIX, FX, von Willebrand factor (VWF), antithrombin, protein C, protein S and fibrinogen in 2177 cases and 2826 controls.
High levels of FT4 were associated with increased concentrations of procoagulant factors, and not with levels of anticoagulant factors. High levels of FT4 were also associated with the risk of venous thrombosis, up to an odds ratio (OR) of 2.2 (95% confidence interval [CI] 1.0–4.6) for levels above 24.4 pm relative to FT4 levels between 15.5 and 18.9 pm. In 11 cases and one control, clinical hyperthyroidism had been diagnosed within a year of the thrombotic event, leading to an OR of 17.0 (95% CI 2.2–133.0) for thrombosis. The ORs approached unity after adjustment for FVIII and VWF, which suggests that the effect was mediated by these factors. Low TSH levels were also, but less evidently, associated with thrombosis, whereas there was no association between antiTPO and venous thrombosis risk.
High levels of FT4 increase the concentrations of the procoagulant proteins FVIII, FIX, fibrinogen, and VWF, and by this mechanism increase the risk of venous thrombosis.