title: Fibrin clot properties in women heterozygous for factor V Leiden mutation: effects of oral contraceptives.
abstract: BACKGROUND
  Oral contraceptives (OC) in the presence of factor V Leiden mutation (FVL) markedly increase the risk of venous thromboembolism (VTE). Little is known about the OC and FVL-related alterations in fibrin clot properties.
  
  
  METHODS
  Plasma fibrin clot permeability (K(s)) and efficiency of lysis, reflected by clot lysis time (CLT) and the rate of D-dimer release from clots (D-D(rate)) induced by recombinant tissue plasminogen activator (tPA) were determined in 25 women with a family history of VTE who were heterozygous for FVL [FVL(+/-) - twice, on third-generation OC and after their discontinuation. Female non-carriers of FVL, matched for demographics, using OC and after their discontinuation served as controls (n=25). All participants had no personal history of VTE.
  
  
  RESULTS
  OC discontinuation in FVL(+/-) women resulted in shortened CLT (-9%), and increased K(s) (+4%) and D-D(rate) (+1.4%; all p<0.01). Alterations in fibrin clot properties were associated with decreased prothrombin fragments 1+2 (F1+2) (-8%), plasminogen activator inhibitor-1 (PAI-1) antigen (-11%), and thrombin activatable fibrinolysis inhibitor (TAFI) activity (-20%; all p<0.01). During OC use FVL(+/-) carriers compared with non-carriers had higher platelet count, activity of PAI-1, TAFI, and tPA, as well as prolonged CLT and higher D-D(max), along with lower D-D(rate) and K(s). Multiple regression analysis adjusted for fibrinogen and age, showed that PAI-1 antigen and TAFI activity independently predicted CLT in FVL(+/-) women on OC.
  
  
  CONCLUSIONS
  FVL(+/-) is associated with hypofibrinolysis in apparently healthy women and third-generation OC administration unfavorably alters plasma clot characteristics in female FVL(+/-) carriers with a family history of thrombotic events.
authors.affiliation: Institute of Cardiology, Jagiellonian University School of Medicine, and the John Paul II Hospital, Krakow, Poland.
authors.forename: Marzena
authors.initials: M
authors.lastname: Krzek
authors.forename: Mariola
authors.initials: M
authors.lastname: Ciesla-Dul
authors.forename: Michal
authors.initials: M
authors.lastname: Zabczyk
authors.forename: Anetta
authors.initials: A
authors.lastname: Undas
mesh_terms: D000328:Adult; D016022:Case-Control Studies; D003276:Contraceptives, Oral / Q000009:adverse effects / Q000494:pharmacology*; D005165:Factor V / Q000235:genetics*; D005260:Female; D005337:Fibrin / Q000378:metabolism*; D063285:Fibrin Clot Lysis Time; D005338:Fibrin Fibrinogen Degradation Products / Q000378:metabolism; D005342:Fibrinolysis / Q000187:drug effects*; D006579:Heterozygote; D006801:Humans; D054556:Venous Thromboembolism / Q000235:genetics* / Q000378:metabolism; D055815:Young Adult
chemical_list: D003276:Contraceptives, Oral; D005338:Fibrin Fibrinogen Degradation Products; C095381:factor V Leiden; C036309:fibrin fragment D; D005165:Factor V; D005337:Fibrin