title: The specific activity of plasminogen activator inhibitor-1 in disseminated intravascular coagulation with acute promyelocytic leukemia.
abstract: In disseminated intravascular coagulation (DIC) with acute promyelocytic leukemia (APL) in the absence of severe infection, marked fibrinolysis was noted in comparison with normal levels of antithrombin III, which is a major inhibitor of the coagulation system. Increased plasminogen activator inhibitor-1 (PAI-1) antigen levels in plasma from patients with septicemia decreased the ratio of the plasma clot lysis rate induced by an anti-alpha 2-plasmin inhibitor monoclonal antibody to the tissue-type plasminogen activator (t-PA) concentration. This decrease was not as prominent in plasma from patients with DIC, especially those with APL. To explore the character of PAI-1 in these plasmas, we measured the specific activity of PAI-1 by determining the ratio of active PAI-1 antigen to t-PA-unbound PAI-1 antigen. To calculate the amount of active PAI-1 antigen, the amount of t-PA/PAI-1 complex before and after the addition of a fixed amount of t-PA to the sample was measured by a sandwich solid-phase enzyme-linked immunosorbent assay using anti-PAI-1 and anti-t-PA monoclonal antibodies. The assay to measure total PAI-1 antigen used three monoclonal anti-PAI-1 antibodies and had similar sensitivities to free active, latent, vitronectin-bound and t-PA-bound PAI-1. The specific activity of PAI-1 decreased in patients with DIC (43.7% +/- 30.6%) and in DIC cases with APL (10.3% +/- 6.0%) in comparison to patients with septicemia (83.7% +/- 20.2%) or normal controls (85.8% +/- 27.3%). In DIC associated with APL, degraded forms of PAI-1 were detected in plasma by immunoblotting. These results suggest that a decrease in the specific activity of PAI-1 and an increase in secondary fibrinolysis result in a hyperfibrinolytic state in DIC patients with APL.
authors.affiliation: Division of Thrombosis and Hemostasis, Jichi Medical School, Tochigi-ken, Japan.
authors.forename: Y
authors.initials: Y
authors.lastname: Sakata
authors.forename: T
authors.initials: T
authors.lastname: Murakami
authors.forename: A
authors.initials: A
authors.lastname: Noro
authors.forename: K
authors.initials: K
authors.lastname: Mori
authors.forename: M
authors.initials: M
authors.lastname: Matsuda
mesh_terms: D000911:Antibodies, Monoclonal; D004211:Disseminated Intravascular Coagulation / Q000097:blood* / Q000209:etiology; D004797:Enzyme-Linked Immunosorbent Assay; D005342:Fibrinolysis; D006023:Glycoproteins / Q000378:metabolism; D006801:Humans; D015151:Immunoblotting; D015473:Leukemia, Promyelocytic, Acute / Q000150:complications*; D015849:Plasminogen Inactivators / Q000097:blood*; D018805:Sepsis / Q000097:blood; D010959:Tissue Plasminogen Activator / Q000378:metabolism; D019096:Vitronectin
chemical_list: D000911:Antibodies, Monoclonal; D006023:Glycoproteins; D015849:Plasminogen Inactivators; D019096:Vitronectin; D010959:Tissue Plasminogen Activator