title: Effect of tamoxifen on measurements of hemostasis in healthy women.
abstract: BACKGROUND
  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.
  
  
  METHODS
  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.
  
  
  RESULTS
  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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Angelo Bianchi Bonomi Hemophilia and Thrombosis Center, Milano, Italy.
authors.forename: P M
authors.initials: PM
authors.lastname: Mannucci
authors.forename: D
authors.initials: D
authors.lastname: Bettega
authors.forename: V
authors.initials: V
authors.lastname: Chantarangkul
authors.forename: A
authors.initials: A
authors.lastname: Tripodi
authors.forename: V
authors.initials: V
authors.lastname: Sacchini
authors.forename: U
authors.initials: U
authors.lastname: Veronesi
mesh_terms: D000284:Administration, Oral; D000328:Adult; D000368:Aged; D018931:Antineoplastic Agents, Hormonal / Q000494:pharmacology* / Q000627:therapeutic use; D001772:Blood Cell Count / Q000187:drug effects; D001777:Blood Coagulation / Q000187:drug effects*; D001779:Blood Coagulation Factors / Q000187:drug effects; D001943:Breast Neoplasms / Q000517:prevention & control*; D004311:Double-Blind Method; D004965:Estrogen Antagonists / Q000494:pharmacology* / Q000627:therapeutic use; D005260:Female; D005342:Fibrinolysis / Q000187:drug effects; D006801:Humans; D007044:Hysterectomy; D008055:Lipids / Q000097:blood; D008875:Middle Aged; D012016:Reference Values; D013629:Tamoxifen / Q000494:pharmacology* / Q000627:therapeutic use
chemical_list: D018931:Antineoplastic Agents, Hormonal; D001779:Blood Coagulation Factors; D004965:Estrogen Antagonists; D008055:Lipids; D013629:Tamoxifen