title: Venous thromboembolism during pregnancy is not associated with persistent elevated activated protein C (APC) sensitivity ratio based on the endogenous thrombin potential.
abstract: Women who are using oral contraceptives can acquire APC resistance, measured by the effect of APC on the endogenous thrombin potential (ETP). The objective of our study was to examine whether persistentAPC resistance determined with an ETP-based normalized APC sensitivity ratio (nAPCsr) is a risk marker for venous thromboembolism in women with pregnancy-associated thromboembolism. We determined the activities of antithrombin, protein C, protein S, and performed a genetic analysis of factor V Leiden G1691A, prothrombin mutation G20210A, and methylenetetrahydrofolate reductase mutation (MTHFR C677T) in 65 women with venous thromboembolism during pregnancy or the puerperium and in 114 normal women. A significantly (p<0.05) higher nAPCsr was present in normal women using hormones, in younger women (<or=45 yrs), and in women with carrier status of factorV Leiden. In normal women without factor V Leiden a significant (p<0.05) negative correlation of nAPCsr with age (r=-0.39), antithrombin activity (r=-0.38), protein S activity (r=-0.26), and a significant positive correlation with hormone intake (r=0.36) was present. nAPCsr is influenced by several coagulation parameters, which are modified by the use of oral contraceptives. Consequently, a multivariate analysis of our data did not show a significant association of nAPCsr to venous thromboembolism, neither as a continuous variable (odds ratio 0.8, 95% CI 0.6-1.1, p=0.10) nor using a cutoff value (nAPCsr cut-off 3.1: odds ratio 1.2, 95% CI 0.3-5.3, p=0.77). Our study demonstrates that nAPCsr is not a risk marker for pregnancy-associated venous thromboembolism.
authors.affiliation: Department of Haemostasis and Transfusion Medicine, Heinrich Heine University Medical Center, Düsseldorf, Germany. zotz@med.uni-duesseldorf.de
authors.forename: Rainer B
authors.initials: RB
authors.lastname: Zotz
authors.forename: Andrea
authors.initials: A
authors.lastname: Gerhardt
authors.forename: Cornelis
authors.initials: C
authors.lastname: Kluft
authors.forename: Rüdiger E
authors.initials: RE
authors.lastname: Scharf
mesh_terms: D020016:Activated Protein C Resistance / Q000150:complications / Q000175:diagnosis*; D000328:Adult; D005260:Female; D006801:Humans; D015999:Multivariate Analysis; D011247:Pregnancy; D011249:Pregnancy Complications, Cardiovascular / Q000097:blood / Q000209:etiology*; D011250:Pregnancy Complications, Hematologic / Q000097:blood*; D011486:Protein C; D012307:Risk Factors; D013917:Thrombin / Q000502:physiology*; D013923:Thromboembolism / Q000097:blood / Q000209:etiology*; D019851:Thrombophilia / Q000175:diagnosis; D020246:Venous Thrombosis / Q000097:blood / Q000209:etiology*
chemical_list: D011486:Protein C; D013917:Thrombin