Anti‐platelet and anti‐thrombotic effects of selective estrogen receptor modulator tamoxifen

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 signaling machinery has not been elucidated in detail. In the present report we show that both tamoxifen and its metabolite 4 OH‐tamoxifen are endowed with potent anti‐platelet properties. 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 control dimethylsulfoxide (vehicle). These findings strongly suggest that tamoxifen significantly downregulates platelet responses and holds potential as a promising anti‐platelet/anti‐thrombotic agent.