title: Acquired activated protein C resistance in postmenopausal women is dependent on factor VIII:c levels.
abstract: Activated protein C (APC) resistance is an established risk factor for venous thromboembolism. In 5% to 10% of patients with venous thromboembolism, the APC resistance phenotype is observed in the absence of factor V Leiden mutation. Moreover, some physiologic and pathologic conditions are associated with an "acquired" APC resistance, not caused by the Leiden mutation, such as inflammatory diseases, pregnancy, or oral contraceptive therapy. Several studies have demonstrated the effect of menopause on the hemostatic system, but no data are available about APC resistance. We found a high prevalence of APC resistance in postmenopausal women, not associated with factor V Leiden mutation. The mechanism that underlies this acquired APC resistance may be related to the higher levels of factor VIII, which showed a strong inverse correlation with APC resistance, whereas no correlation was found between the normalized APC ratio, factor V levels, and protein S values. Higher levels of factor VIII correlated with a marker of coagulation activation, such as prothrombin fragments 1 plus 2. Therefore, to identify women receiving hormone replacement therapy who have a greater risk for deep venous thrombosis, the APC resistance coagulation test should be used instead of the genetic study.
authors.affiliation: Istituto di Clinica Medica Generale e Cardiologia, Università di Firenze, Italy.
authors.forename: R
authors.initials: R
authors.lastname: Marcucci
authors.forename: R
authors.initials: R
authors.lastname: Abbate
authors.forename: S
authors.initials: S
authors.lastname: Fedi
authors.forename: A M
authors.initials: AM
authors.lastname: Gori
authors.forename: T
authors.initials: T
authors.lastname: Brunelli
authors.forename: V
authors.initials: V
authors.lastname: Bruni
authors.forename: S
authors.initials: S
authors.lastname: Bucciantini
authors.forename: S
authors.initials: S
authors.lastname: Micheli
authors.forename: G
authors.initials: G
authors.lastname: Pepe
authors.forename: D
authors.initials: D
authors.lastname: Prisco
authors.forename: G F
authors.initials: GF
authors.lastname: Gensini
mesh_terms: D020016:Activated Protein C Resistance / Q000097:blood*; D000328:Adult; D005165:Factor V / Q000032:analysis; D005169:Factor VIII / Q000032:analysis*; D005260:Female; D020249:Hormone Replacement Therapy / Q000009:adverse effects; D006801:Humans; D008875:Middle Aged; D017698:Postmenopause / Q000097:blood*; D012307:Risk Factors; D020246:Venous Thrombosis / Q000453:epidemiology
chemical_list: C095381:factor V Leiden; D005165:Factor V; D005169:Factor VIII