title: The APC-PCI concentration as an early marker of activation of blood coagulation: a study of women on combined oral contraceptives.
abstract: BACKGROUND
  The risk of venous tromboembolism (VTE) in women taking combined oral contraceptives (COCs) is attributed to changes in coagulation and fibrinolysis. The impact of the COCs may be greater in women with preexisting thrombophilic defects. Nevertheless most women who suffer from venous thrombosis do not have any of the well known hereditary or acquired risk factors. A simple and sensitive marker of"thrombogenicity" has not been identified.
  
  
  OBJECTIVE
  To investigate the effects of two different monophasic combined oral contraceptives (COCs) on the plasma concentrations of activated protein C-inhibitor of protein C ( APC-PCI) and on comparable hemostatic factors in fertile women.
  
  
  METHODS
  Forty four healthy nulliparous women with regular menstrual periods were included and randomly assigned to start with a monophasic preparation containing 30μg ethinylestradiol and 150μg levonogestrel (LNG/EE) or a preparation containing 30μg ethinylestradiol and 150 ug desogestrel (DG/EE). After a wash out period of two months, treatment with the alternate preparation was initiated and continued for two more cycles.
  
  
  RESULTS
  The plasma concentration of the APC-PCI complex and thrombin-antithrombin complex (TAT) increased during treatment with the two COCs. During DG/EE treatment the APC-PCI complex increased significantly more than during LNG/EE (p<0,01).The plasma concentration of D-dimer did not increase during OC treatment.
  
  
  CONCLUSIONS
  The APC-PCI complex concentration, which serves as a marker for thrombin generation and indicates hypercoagulability, was increased during COC treatment compared to baseline. The method is a sufficiently sensitive marker to detect even small differences in the activation of coagulation.
authors.affiliation: Department of Women´s and Children´s Health, Division of Obstetrics and Gynecology Karolinska Institutet, Stockholm, Sweden. Katarina.Bremme@karolinska.se
authors.forename: K
authors.initials: K
authors.lastname: Bremme
authors.forename: R Rafik
authors.initials: RR
authors.lastname: Hamad
authors.forename: Elisabeth
authors.initials: E
authors.lastname: Berg
authors.forename: K
authors.initials: K
authors.lastname: Strandberg
authors.forename: J
authors.initials: J
authors.lastname: Stenflo
mesh_terms: D000328:Adult; D000990:Antithrombin III; D001777:Blood Coagulation / Q000187:drug effects; D003277:Contraceptives, Oral, Combined / Q000009:adverse effects* / Q000494:pharmacology; D017135:Desogestrel / Q000009:adverse effects* / Q000494:pharmacology; D004997:Ethinyl Estradiol / Q000009:adverse effects* / Q000494:pharmacology; D005260:Female; D005338:Fibrin Fibrinogen Degradation Products / Q000032:analysis; D006801:Humans; D016912:Levonorgestrel / Q000009:adverse effects* / Q000494:pharmacology; D010447:Peptide Hydrolases / Q000097:blood; D011486:Protein C / Q000032:analysis; D018046:Protein C Inhibitor / Q000097:blood; D019851:Thrombophilia / Q000139:chemically induced* / Q000175:diagnosis; D055815:Young Adult
chemical_list: D003277:Contraceptives, Oral, Combined; D005338:Fibrin Fibrinogen Degradation Products; D011486:Protein C; D018046:Protein C Inhibitor; C046193:antithrombin III-protease complex; C036309:fibrin fragment D; D004997:Ethinyl Estradiol; D016912:Levonorgestrel; D017135:Desogestrel; D000990:Antithrombin III; D010447:Peptide Hydrolases