New Interfaces of Thyroid Hormone Actions With Blood Coagulation and Thrombosis

Abstract

Substantial clinical evidence indicates hyperthyroidism enhances coagulation and increases the risk of thrombosis. In vitro and clinical evidence implicate multiple mechanisms for this risk. Genomic actions of thyroid hormone as 3,5,3'-triiodo-L-thyronine (T) via a nuclear thyroid hormone receptor have been implicated, but recent evidence shows that nongenomic mechanisms initiated at the receptor for L-thyroxine (T) on platelet integrin αvβ3 are prothrombotic. The T-initiated mechanisms involve platelet activation and, in addition, cellular production of cytokines and chemokines such as CX3CL1 with procoagulatory activities. These procoagulant actions of T are particulary of note because within cells T4 is not seen to be functional, but to be only a prohormone for T. Finally, it is also possible that thyroid hormone stimulates platelet-endothelial cell interaction involved in local thrombus generation. In this brief review, we survey mechanisms by which thyroid hormone is involved in coagulation and platelet functions. It is suggested that the threshold should be lowered for considering the possibility that clinically significant clotting may complicate hyperthyroidism. The value of routine measurement of partial thromboplastin time or circulating D-dimer in patients with hyperthyroid or in patients treated with thyrotropin-suppressing dosage of T requires clinical testing.

Is There a Role for Levo-Thyroxine for the Treatment of Arterial Erectile Dysfunction? The Clinical Relevance of the Mean Platelet Volume

“…THRs are expressed in hematopoietic stem cells and thyroid hormones can modulate the production of blood cells, including platelets. Thyroid hormones are able to initiate platelet aggregation by the interaction with the VR and endothelium adhesion [19]. This explains the association between overt hyperthyroidism and the risk of thrombosis.…”

Thyroid gland dysfunction and its effect on the cardiovascular system: a comprehensive review of the literature

“…At the cellular level, platelets express protein avb3 that contain receptors for T4 hormone but not for T3. Therefore, hyperthyroidism increases platelet aggregation and increases the risk of thromboembolism [2,[32][33][34]. Also, platelet aggregation is induced by CX3CL1, a chemokine that is regulated from avb3 by T4 and thus increases pathologic clotting [34][35][36].…”

“…Therefore, hyperthyroidism increases platelet aggregation and increases the risk of thromboembolism [2,[32][33][34]. Also, platelet aggregation is induced by CX3CL1, a chemokine that is regulated from avb3 by T4 and thus increases pathologic clotting [34][35][36]. Angioinvasion, a prothrombotic state could also contribute to this hypercoagulable state [37,38].…”

Anti-integrins

“…Certain integrins have been implicated in ophthalmologic diseases and have been considered targets for anti-integrins (Gonzalez-Salinas et al 2018). Finally, there are thrombotic conditions in which anti-integrins have been mentioned as possible therapeutic interventions (Mousa et al 2010;Davis et al 2018a;Mousa et al 2018;Davis et al 2018b). Because normal platelets bear avb3 that originated in the plasma membrane of the megakaryocyte, thyroid hormone action on platelet aggregation via avb3 might be a source of hypercoaguability (Mousa et al 2010).…”