Effect of Tamoxifen and Raloxifene on platelet activation markers

Abstract

Tamoxifen (TAM) and Raloxifene (RAL) are structurally related non‐steroidal estrogens used for prevention of breast cancer. However, thrombosis is as an adverse effect of both drugs. The goal of the study was to determine effect of TAM and RAL on platelets in whole unfractionated blood. Activation markers expression (Annexin V binding, P‐selectin expression and PAC‐1 binding) in TAM‐ and RAL‐ treated platelets was measured. 1uM TAM increased double positive platelets (CD62/PAC‐1) by 19±5% while 1uM RAL increased by 20±7%. In combination with 1uM TRAP6, both TAM and RAL at 10 uM increased TRAP6 induced elevation of CD62/PAC‐1 expression (TRAP6, 43±11%; TAM+TRAP6, 108±44%; RAL+TRAP6, 120±39%). Both TAM and RAL increased Annexin V binding (1.3±0.6% baseline, 10 uM TAM 4.7±1.5%, 10 uM RAL 5.2±1.7%). ADP at 5 uM induced 2.7±0.7% Annexin V binding; ADP+10 uM TAM was 5.8±1.7%, and ADP+10 uM RAL was 7±2%. Both drugs stimulate expression of platelet activation markers and sensitize platelets to agonists. This provides a possible mechanism of thrombosis in patients taking RAL and TAM for the prevention of breast cancer (Supported by the SDG from the AHA, CHRB and Cancer Research and Prevention Foundation).