title: Plasma factor VII-activating protease is increased by oral contraceptives and induces factor VII activation in-vivo.
abstract: Oral contraceptive (OC) use influences the hemostatic system significantly and is a risk factor for development of cardiovascular disease. Factor VII-activating protease (FSAP) has potential effects on hemostasis. The 1601GA genotype of the 1601G/A polymorphism in the FSAP gene expresses a FSAP alloenzyme with reduced pro-fibrinolytic activity. Presently, we address whether OC use and OC formulation affect FSAP measures in human blood. Healthy women (n=588) were allocated to six cycles of OCs with estrogen contents of 20 μg (n=158), 30 μg (n=284), 35 μg (n=79) or 50 μg (n=67) combined with various progestins. FSAP genotypes, FSAP and factor VII (FVII) plasma measures were assessed at baseline and after 6 cycles of OC. The 1601GA genotype was present in 49 (8.3%) of the women and was associated with significantly reduced levels of FSAP (P≤0.001). OC use increased FSAP antigen by 25% and FSAP activity by 59% (P<0.001). The FSAP increase was comparable in the seven different OC treatment groups (P>0.05). The relative increase in FSAP activity was significantly higher in women carrying the 1601GG genotype (63%) than in women carrying 1601GA genotype (50%) (P=0.01) and was associated with an increased activation of FVII.
  
  
  CONCLUSIONS
  OC use increases the plasma measures of FSAP. The increase in FSAP is comparable in the seven OC-groups studied but is more significant in women carrying the 1601GG genotype than in women with the 1601GA genotype and results in increased activation of FVII suggesting that FSAP-induced activation of FVII takes place in-vivo and not only in-vitro as hitherto described.
authors: Unit for Thrombosis Research, Institute of Public Health, University of Southern Denmark, Esbjerg, Denmark. jjsidelmann@health.sdu.dk
authors: Johannes J
authors: JJ
authors: Sidelmann
authors: Sven O
authors: SO
authors: Skouby
authors: Cornelis
authors: C
authors: Kluft
authors: Ulrich
authors: U
authors: Winkler
authors: Frank
authors: F
authors: Vitzthum
authors: Herbert
authors: H
authors: Schwarz
authors: Jørgen
authors: J
authors: Gram
authors: Jørgen
authors: J
authors: Jespersen
mesh_terms: D000328:Adult; D003276:Contraceptives, Oral / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D004967:Estrogens / Q000008:administration & dosage / Q000494:pharmacology; D005167:Factor VII / Q000378:metabolism*; D015942:Factor VIIa / Q000378:metabolism*; D005260:Female; D005838:Genotype; D006801:Humans; D012697:Serine Endopeptidases / Q000097:blood* / Q000235:genetics; D055815:Young Adult
chemical_list: D003276:Contraceptives, Oral; D004967:Estrogens; D005167:Factor VII; C433550:HABP2 protein, human; D012697:Serine Endopeptidases; D015942:Factor VIIa