title: Hypofibrinolysis in patients with hypercoagulability: the roles of urokinase and of plasminogen activator inhibitor.
abstract: The prevalence of abnormalities of fibrinolysis in patients with venous thromboembolism is as yet unknown. Defined abnormalities include congenital dysfunction and deficiency of plasminogen, and probably impaired plasminogen activation secondary to elevated levels of plasminogen activator inhibitor type 1 (PAI-1) or to impaired release of tissue plasminogen activator (tPA). In this preliminary study, we analyzed plasma samples from 21 patients for whom an investigation for possible thrombophilia was requested. Twenty of the patients had venous thromboembolism, and one had arterial thrombosis at an early age. Two patients had deficiency of protein C or protein S, but no other recognized biochemical disturbances related to thrombophilia were identified. Patient samples and plasma from 25 normal controls were assayed for tPA activity, PAI-1 activity, and urokinase (uPA) activity and antigen. tPA activity and antigen were not significantly different in patients than in controls. PAI-1 activity was significantly greater in patients (P < 0.0001). uPA activity was not different in the two groups. However, uPA antigen was significantly reduced in patients compared to controls (P = 0.001). These data suggest that hypofibrinolysis leading to a risk of thrombosis may be caused not only by elevated PAI-1 activity but also by reduced total uPA concentration.
authors.affiliation: Division of Hematology, St. Michael's Hospital, Toronto, Ontario, Canada.
authors.forename: H K
authors.initials: HK
authors.lastname: Lau
authors.forename: J M
authors.initials: JM
authors.lastname: Teitel
authors.forename: T
authors.initials: T
authors.lastname: Cheung
authors.forename: S K
authors.initials: SK
authors.lastname: Kung
authors.forename: M B
authors.initials: MB
authors.lastname: Garvey
mesh_terms: D000328:Adult; D000368:Aged; D004792:Enzyme Precursors / Q000097:blood; D005260:Female; D005342:Fibrinolysis; D006801:Humans; D008297:Male; D008875:Middle Aged; D017395:Plasminogen Activator Inhibitor 1 / Q000097:blood*; D011486:Protein C / Q000032:analysis; D020151:Protein C Deficiency; D017293:Protein S / Q000032:analysis; D018455:Protein S Deficiency; D012016:Reference Values; D013923:Thromboembolism / Q000097:blood*; D014568:Urokinase-Type Plasminogen Activator / Q000097:blood*
chemical_list: D004792:Enzyme Precursors; D017395:Plasminogen Activator Inhibitor 1; D011486:Protein C; D017293:Protein S; D014568:Urokinase-Type Plasminogen Activator