title: Detection of decreased response to activated protein C during pregnancy by an endogenous thrombin potential-based assay.
abstract: Pregnancy has been widely recognized as a predisposing risk factor for deep vein thrombosis (DVT). However, it still remains unclear why pregnant women without a history of familial thrombophilia or antiphospholipid syndrome (APS) have a higher incidence of DVT and pulmonary embolism (PE) during pregnancy and puerperium. We examined the activated protein C (APC) system in healthy pregnant women and in patients with the onset of DVT during puerperium. Sixty unselected Japanese pregnant women without a past or family history of thrombosis or APS and 3 Japanese women with DVT during puerperium were evaluated. Endogenous thrombin potential-ratio (ETP-r) was measured by determination of thrombin-alpha2-macroglobulin complexes in thromboplastin-activated patient plasma. APC sensitivity ratio (APC-sr) was calculated by the determination of ETP-r in patient plasma in the presence and absence of APC (final concentration [conc.] 5.9 nM) to evaluate the functional APC anticoagulant activity. Mean APC-sr was significantly increased at 30 weeks' gestation (2.35 +/- 0.72) and remained high during puerperium compared with the mean APC-sr in nonpregnant women (1.15 +/- 0.63). Mean APC-sr in patients with DVT at the onset was significantly higher (3.57 +/- 0.54) than mean APC-sr during puerperium was, indicating that the sensitivity to APC was reduced in the ETP-based assay. These data suggest a significant reduction in the functional sensitivity to APC associated with an increased risk of venous thrombosis during pregnancy.
authors.affiliation: Department of Obstetrics and Gynecology, Hamamatsu University, School of Medicine, Japan.
authors.forename: M
authors.initials: M
authors.lastname: Sugimura
authors.forename: T
authors.initials: T
authors.lastname: Kobayashi
authors.forename: N
authors.initials: N
authors.lastname: Kanayama
authors.forename: T
authors.initials: T
authors.lastname: Terao
mesh_terms: D020016:Activated Protein C Resistance / Q000175:diagnosis*; D000933:Antifibrinolytic Agents / Q000097:blood; D000941:Antigens / Q000097:blood; D000990:Antithrombin III / Q000032:analysis; D005260:Female; D005338:Fibrin Fibrinogen Degradation Products / Q000032:analysis; D005865:Gestational Age; D006400:Hematocrit; D006801:Humans; D007564:Japan / Q000453:epidemiology; D010447:Peptide Hydrolases / Q000032:analysis; D010976:Platelet Count; D049590:Postpartum Period; D011247:Pregnancy; D011250:Pregnancy Complications, Hematologic / Q000378:metabolism*; D017293:Protein S / Q000378:metabolism; D013917:Thrombin / Q000378:metabolism; D020246:Venous Thrombosis / Q000209:etiology*; D000515:alpha 1-Antitrypsin / Q000276:immunology; D000511:alpha-Macroglobulins / Q000378:metabolism
chemical_list: D000933:Antifibrinolytic Agents; D000941:Antigens; D005338:Fibrin Fibrinogen Degradation Products; D017293:Protein S; D000515:alpha 1-Antitrypsin; D000511:alpha-Macroglobulins; C046193:antithrombin III-protease complex; C036309:fibrin fragment D; D000990:Antithrombin III; D010447:Peptide Hydrolases; D013917:Thrombin