Plasma factor VII-activating protease is increased by oral contraceptives and induces factor VII activation in-vivo

Thromb Res. 2011 Nov;128(5):e67-72. doi: 10.1016/j.thromres.2011.06.013. Epub 2011 Jul 6.


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.

In conclusion: 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.

Publication types

  • Clinical Trial
  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Contraceptives, Oral / pharmacology*
  • Dose-Response Relationship, Drug
  • Estrogens / administration & dosage
  • Estrogens / pharmacology
  • Factor VII / metabolism*
  • Factor VIIa / metabolism*
  • Female
  • Genotype
  • Humans
  • Serine Endopeptidases / blood*
  • Serine Endopeptidases / genetics
  • Young Adult


  • Contraceptives, Oral
  • Estrogens
  • Factor VII
  • HABP2 protein, human
  • Serine Endopeptidases
  • Factor VIIa