title: Tamoxifen-induced tissue factor pathway inhibitor reduction: a clue for an acquired thrombophilic state?
abstract: BACKGROUND
  Current understanding of hemostatic systems enables us to better explore the enigmatic pathobiology of tamoxifen (TAM)-induced thrombotic diathesis. We have therefore aimed to assess the hemostatic changes in breast cancer patients receiving TAM on an adjuvant basis.
  
  
  METHODS
  The study population consisted of 43 female patients with hormone receptor-positive breast cancer who received TAM 20 mg/day as part of their adjuvant treatment. Mean age was 52+/-12 years (range 25-74). Twenty-one patients (49%) were premenopausal. Plasma samples were collected prior to and following 6 months of TAM therapy and were assayed for total tissue factor pathway inhibitor (TFPI), free TFPI, lipid-bound TFPI, thrombomodulin, D dimer, activated protein C resistance (APC res), factors VIIa, II, V, VII and X, and global fibrinolytic capacity (GFC).
  
  
  RESULTS
  Median total TFPI decreased significantly from 48.5 ng/ml to 36.2 ng/ml (P=0.001), free TFPI from 10 to 7.6 ng/ml (P=0.001) and lipid-bound TFPI from 39.1 to 28.7 ng/ml (P=0.001). There were significant decreases in the levels of factor II (P=0.03), factor V (P=0.001), factor VII (P=0.06), thrombomodulin (P=0.01) and D dimer (P=0.001). However, APC res times were significantly prolonged (P=0.04). The remaining parameters that we have studied were not significantly affected.
  
  
  CONCLUSIONS
  Our findings suggest that TAM tends to activate the coagulation pathway by counteracting major molecules involved in coagulation inhibition, namely TFPI and TM. As reflected by unchanged GFC, the drug appears to impair the expected compensatory activation of the fibrinolytic system, which removes fibrin polymers resulting from coagulation activation.
authors.affiliation: Institute of Oncology, Section of Medical Oncology, Hacettepe University, Ankara, Turkey.
authors.forename: M
authors.initials: M
authors.lastname: Erman
authors.forename: H
authors.initials: H
authors.lastname: Abali
authors.forename: B
authors.initials: B
authors.lastname: Oran
authors.forename: I C
authors.initials: IC
authors.lastname: Haznedaroglu
authors.forename: H
authors.initials: H
authors.lastname: Canpinar
authors.forename: S
authors.initials: S
authors.lastname: Kirazli
authors.forename: I
authors.initials: I
authors.lastname: Celik
mesh_terms: D020016:Activated Protein C Resistance / Q000378:metabolism; D000328:Adult; D000368:Aged; D018931:Antineoplastic Agents, Hormonal / Q000009:adverse effects* / Q000627:therapeutic use; D001943:Breast Neoplasms / Q000188:drug therapy*; D005165:Factor V / Q000378:metabolism; D005167:Factor VII / Q000378:metabolism; D015942:Factor VIIa / Q000378:metabolism; D005170:Factor X / Q000378:metabolism; D005260:Female; D005338:Fibrin Fibrinogen Degradation Products / Q000378:metabolism; D005342:Fibrinolysis / Q000187:drug effects; D006801:Humans; D008074:Lipoproteins / Q000097:blood; D008593:Menopause / Q000097:blood / Q000187:drug effects; D008875:Middle Aged; D009367:Neoplasm Staging; D011516:Prothrombin / Q000378:metabolism; D013629:Tamoxifen / Q000009:adverse effects* / Q000627:therapeutic use; D018180:Thrombomodulin / Q000097:blood; D019851:Thrombophilia / Q000139:chemically induced*; D013997:Time Factors; D016896:Treatment Outcome
chemical_list: D018931:Antineoplastic Agents, Hormonal; D005338:Fibrin Fibrinogen Degradation Products; D008074:Lipoproteins; D018180:Thrombomodulin; C036309:fibrin fragment D; C051928:lipoprotein-associated coagulation inhibitor; D013629:Tamoxifen; D005165:Factor V; D005167:Factor VII; D011516:Prothrombin; D005170:Factor X; D015942:Factor VIIa