THE INFLUENCE OF TAMOXIFEN IN-VIVO ON THE MAIN NATURAL ANTICOAGULANTSAND FIBRINOLYSIS

The long-term effects of tamoxifen on alterations in haemostasis which could lead towards thrombosis were investigated in 149 women who were disease-free for at least 5 years following mastectomy for breast can cer. All participants were randomized to receive tamoxifen as a post-s urgical adjuvant treatment (89 patients, treated group) or not (60 pat ients, controls) for at least 2 years. 5.62% of the cases treated with tamoxifen suffered a venous thrombosis, while no thromboembolism was reported in the control group. No significant differences were observe d between groups in the global clotting times, fibrinogen, fibrinolyti c factors, or in the concentration of the main natural anticoagulants, antithrombin III (AT-III), protein C (PC) and protein S (PS). However , when the treated group was sub-divided, current users (n = 18) of th e drug (median treatment duration 72 months) had significantly lower A T-III (P < 0.05) and PC (P < 0.05) activities, together with higher le vels of plasminogen activity (P < 0.01) and tissue plasminogen activat or antigen (P < 0.01), compared with 71 ex-users (who mostly received treatment for 2 years) and controls. We conclude that long-term treatm ent with tamoxifen for 2 or more years tends to reduce both AT-III and PC, a situation possibly predisposing towards thrombosis. Monitoring haemostasis in tamoxifen-treated breast cancer patients is therefore a dvisable.