BACKGROUND: Raloxifene therapy is associated with a three-fold increase in the risk for venous thromboembolism; however, its effects on the hemostatic system in postmenopausal women have not been well defined. OBJECTIVE: To determine the effects of raloxifene therapy on the levels of natural anticoagulant proteins in postmenopausal women. METHODS: Sixteen healthy postmenopausal women were enrolled in this prospective longitudinal study. The patients were treated with raloxifene hydrochloride (60 mg/day) for a period of 6 months. Antithrombin and protein C activities and protein S antigen levels were measured in all users at baseline, and after 1, 3 and 6 months of treatment. Statistical analysis included one-way analysis of variance (ANOVA) and the Bonferroni test for multiple comparisons among the study periods. RESULTS: Statistically significant 5.1% and 6.5% reductions of plasma antithrombin activity were observed at 3 and 6 months of therapy, respectively (p < 0.05). Compared with baseline, raloxifene did not significantly affect protein C activity or protein S level. CONCLUSIONS: The results of this prospective study show for the first time that raloxifene use is associated with a significant reduction in plasma antithrombin activity. This effect may contribute to a procoagulant state and partly explain the increased risk of venous thromboembolism in raloxifene users.
BACKGROUND:Raloxifene therapy is associated with a three-fold increase in the risk for venous thromboembolism; however, its effects on the hemostatic system in postmenopausal women have not been well defined. OBJECTIVE: To determine the effects of raloxifene therapy on the levels of natural anticoagulant proteins in postmenopausal women. METHODS: Sixteen healthy postmenopausal women were enrolled in this prospective longitudinal study. The patients were treated with raloxifene hydrochloride (60 mg/day) for a period of 6 months. Antithrombin and protein C activities and protein S antigen levels were measured in all users at baseline, and after 1, 3 and 6 months of treatment. Statistical analysis included one-way analysis of variance (ANOVA) and the Bonferroni test for multiple comparisons among the study periods. RESULTS: Statistically significant 5.1% and 6.5% reductions of plasma antithrombin activity were observed at 3 and 6 months of therapy, respectively (p < 0.05). Compared with baseline, raloxifene did not significantly affect protein C activity or protein S level. CONCLUSIONS: The results of this prospective study show for the first time that raloxifene use is associated with a significant reduction in plasma antithrombin activity. This effect may contribute to a procoagulant state and partly explain the increased risk of venous thromboembolism in raloxifene users.
Authors: Lori Mosca; Deborah Grady; Elizabeth Barrett-Connor; Peter Collins; Nanette Wenger; Beth L Abramson; Annlia Paganini-Hill; Mary Jane Geiger; Sherie A Dowsett; Messan Amewou-Atisso; Marcel Kornitzer Journal: Stroke Date: 2008-10-23 Impact factor: 7.914