Endocrine determinants of haemostasis and thrombosis risk: Focus on thyroid hormone

This thesis explores endocrine determinants of the haemostatic system and thrombosis risk with main focus on thyroid hormone. It describes, in three parts, the effects of thyroid hormone on the haemostatic system, the effects of thyroid hormone (mimetics) on lipids and the effects of other hormones such as parathyroid hormone and prolactin on the haemostatic system and thrombosis risk. This thesis entails both studies on markers of coagulation and fibrinolysis as well as epidemiological studies on clinical endpoints (mainly venous thrombosis and bleeding). Besides, the evidence of the effect of thyroid hormone on the haemostatic system and on the risk of bleeding and venous thrombosis is reviewed. We aimed to elucidate the mechanism by which hyperthyroidism leads to a hypercoagulable state. We observed that the procoagulant effects observed in hyperthyroidism are mediated via the thyroid hormone receptor β (TRβ) which provides further insight into the pathophysiology of the increased risk of venous thrombosis in patients with hyperthyroidism. Based on these results, the question arises whether the use of TRβ-specific thyromimetics (e.g., eprotirome) could be associated with hypercoagulability. Some other findings described in this thesis regard the glucocorticoid receptor (GR) and the use of mineralocorticoid receptor antagonists. The polymorphism 23EK in the GR gene is associated with an increased risk of VTE which suggests that genetically determined cortisol sensitivity might be involved in the pathogenesis of venous thrombosis. Our systematic review and meta-analysis pointed out that mineralocorticoid receptor antagonists can be considered as safe regarding their effects on haemostasis.