Mannucci P M, Bettega D, Chantarangkul V, Tripodi A, Sacchini V, Veronesi U
Angelo Bianchi Bonomi Hemophilia and Thrombosis Center, Milano, Italy.
Arch Intern Med. 1996 Sep 9;156(16):1806-10.
Tamoxifen citrate is being evaluated for primary prevention of breast cancer, but this drug with estrogen-like properties may cause changes in the hemostatic system that would increase the risk of thrombosis.
Women who had undergone hysterectomy were consecutively enrolled in the placebo-controlled, randomized, double-blind Breast Carcinoma Chemoprevention Tamoxifen Study, which was designed to evaluate the efficacy of oral tamoxifen citrate (20 mg/d). Our substudy of hemostasis and lipid measurements included the first 68 consecutive women assigned to tamoxifen (n = 31) or placebo (n = 37). Blood specimens were obtained before treatment and after 1,2,4, and 6 months of treatment. Measurements included blood cell counts, lipid levels, coagulation activation markers, clotting factors, and anticoagulant and fibrinolysis proteins.
Hematocrit and hemoglobin and platelet levels fell slightly but significantly in women treated with tamoxifen. No between-treatment differences were observed in any of the clotting factors. Naturally occurring anticoagulant proteins such as antithrombin and protein C fell slightly in women treated with tamoxifen. However, no significant changes were observed in any of the markers of activated coagulation or fibrinolysis (fibrinopeptide A, prothrombin fragment 1 + 2, thrombin-antithrombin complex, D-dimer). Total and low-density lipoprotein cholesterol levels fell significantly in women treated with tamoxifen.
Tamoxifen induced a modest decrease in anticoagulant proteins, but without biochemical signs of activation of coagulation and fibrinolysis. Tamoxifen improved the lipid profile and induced changes in blood cell counts, which should determine an improvement in blood rheologic factors. These preliminary findings seem to justify continuation of the double-blind study in healthy women, but only direct comparison of thromboembolic complications in the 2 treatment groups will establish whether tamoxifen carries a risk of thrombosis.
枸橼酸他莫昔芬正在被评估用于乳腺癌的一级预防，但这种具有雌激素样特性的药物可能会引起止血系统的变化，从而增加血栓形成的风险。
接受过子宫切除术的女性连续入选安慰剂对照、随机、双盲的乳腺癌化学预防他莫昔芬研究，该研究旨在评估口服枸橼酸他莫昔芬（20毫克/天）的疗效。我们关于止血和血脂测量的子研究纳入了连续分配至他莫昔芬组（n = 31）或安慰剂组（n = 37）的前68名女性。在治疗前以及治疗1、2、4和6个月后采集血标本。测量指标包括血细胞计数、血脂水平、凝血激活标志物、凝血因子以及抗凝和纤溶蛋白。
接受他莫昔芬治疗的女性的血细胞比容、血红蛋白和血小板水平略有下降，但具有显著差异。在任何凝血因子方面均未观察到治疗组间差异。接受他莫昔芬治疗的女性中，诸如抗凝血酶和蛋白C等天然存在的抗凝蛋白略有下降。然而，在任何激活凝血或纤溶的标志物（纤维蛋白肽A、凝血酶原片段1 + 2、凝血酶 - 抗凝血酶复合物、D - 二聚体）方面均未观察到显著变化。接受他莫昔芬治疗的女性的总胆固醇和低密度脂蛋白胆固醇水平显著下降。
他莫昔芬导致抗凝蛋白适度降低，但没有凝血和纤溶激活的生化迹象。他莫昔芬改善了血脂状况并引起血细胞计数变化，这应该会使血液流变学因素得到改善。这些初步发现似乎证明在健康女性中继续进行双盲研究是合理的，但只有直接比较两个治疗组中的血栓栓塞并发症才能确定他莫昔芬是否存在血栓形成风险。
