Anti-thrombotic effects of selective estrogen receptor modulator tamoxifen

Manasa K. Nayak; Sunil K. Singh; Arnab Roy; Vivek Prakash; Anand Kumar; Debabrata Dash

doi:10.1160/TH11-03-0178

Thrombosis and Haemostasis, Table of Contents

Thromb Haemost 2011; 106(04): 624-635
DOI: 10.1160/TH11-03-0178

Blood Coagulation, Fibrinolysis and Cellular Haemostasis

Schattauer GmbH

Anti-thrombotic effects of selective estrogen receptor modulator tamoxifen

Manasa K. Nayak

¹Department of Biochemistry, Institute of Medical Sciences, Banaras Hindu University, Varanasi, India

,

Sunil K. Singh

¹Department of Biochemistry, Institute of Medical Sciences, Banaras Hindu University, Varanasi, India

,

Arnab Roy

¹Department of Biochemistry, Institute of Medical Sciences, Banaras Hindu University, Varanasi, India

,

Vivek Prakash

²Department of General Surgery, Institute of Medical Sciences, Banaras Hindu University, Varanasi, India

,

Anand Kumar

²Department of General Surgery, Institute of Medical Sciences, Banaras Hindu University, Varanasi, India

,

Debabrata Dash

¹Department of Biochemistry, Institute of Medical Sciences, Banaras Hindu University, Varanasi, India

› Author Affiliations

Abstract

Summary

Tamoxifen is a known anti-cancer drug and established estrogen receptor modulator. Few clinical studies have earlier implicated the drug in thrombotic complications attributable to lower anti-thrombin and protein S levels in plasma. However, action of tamoxifen on platelet signalling machinery has not been elucidated in detail. In the present report we show that tamoxifen is endowed with significant inhibitory property against human platelet aggregation. From a series of in vivo and in vitro studies tamoxifen was found to inhibit almost all platelet functions, prolong tail bleeding time in mouse and profoundly prevent thrombus formation at injured arterial wall in mice, as well as on collagen matrix perfused with platelet-rich plasma under arterial shear against the vehicle dimethylsulfoxide (DMSO). These findings strongly suggest that tamoxifen significantly downregulates platelet responses and holds potential as a promising anti-platelet / anti-thrombotic agent.

Keywords

Antiplatelet drug - estrogen receptor - platelet aggregation - selective estrogen receptor modulators (SERM) - thrombosis

Full Text

References

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