title: Plasminogen activation in vivo upon intravenous infusion of DDAVP. Quantitative assessment of plasmin-alpha 2-antiplasmin complex with a novel monoclonal antibody based radioimmunoassay.
abstract: Infusion of desamino-d-arginine vasopressin (DDAVP) results in an increase in plasma plasminogen activator activity. Whether this increase results in the generation of plasmin in vivo has never been established. A novel sensitive radioimmunoassay (RIA) for the measurement of the complex between plasmin and its main inhibitor alpha 2-antiplasmin (PAP complex) was developed using monoclonal antibodies preferentially reacting with complexed and inactivated alpha 2-antiplasmin and monoclonal antibodies against plasmin. The assay was validated in healthy volunteers and in patients with an activated fibrinolytic system. Infusion of DDAVP in a randomized placebo controlled crossover study resulted in all volunteers in a 6.6-fold increase in PAP complex, which was maximal between 15 and 30 min after the start of the infusion. Hereafter, plasma levels of PAP complex decreased with an apparent half-life of disappearance of about 120 min. Infusion of DDAVP did not induce generation of thrombin, as measured by plasma levels of prothrombin fragment F1+2 and thrombin-antithrombin III (TAT) complex. We conclude that the increase in plasminogen activator activity upon the infusion of DDAVP results in the in vivo generation of plasmin, in the absence of coagulation activation. Studying the DDAVP induced increase in PAP complex of patients with thromboembolic disease and a defective plasminogen activator response upon DDAVP may provide more insight into the role of the fibrinolytic system in the pathogenesis of thrombosis.
authors.affiliation: Center for Thrombosis, Haemostasis and Atherosclerosis Research, Academic Medical Center, Amsterdam, The Netherlands.
authors.forename: M
authors.initials: M
authors.lastname: Levi
authors.forename: J P
authors.initials: JP
authors.lastname: de Boer
authors.forename: D
authors.initials: D
authors.lastname: Roem
authors.forename: J W
authors.initials: JW
authors.lastname: ten Cate
authors.forename: C E
authors.initials: CE
authors.lastname: Hack
mesh_terms: D000328:Adult; D000911:Antibodies, Monoclonal; D003894:Deamino Arginine Vasopressin / Q000008:administration & dosage / Q000494:pharmacology*; D004211:Disseminated Intravascular Coagulation / Q000097:blood; D005341:Fibrinolysin / Q000032:analysis / Q000096:biosynthesis / Q000276:immunology; D005342:Fibrinolysis / Q000187:drug effects / Q000502:physiology; D006801:Humans; D066298:In Vitro Techniques; D007262:Infusions, Intravenous; D010958:Plasminogen / Q000378:metabolism*; D011863:Radioimmunoassay / Q000379:methods; D013927:Thrombosis / Q000209:etiology; D000511:alpha-Macroglobulins / Q000032:analysis / Q000276:immunology
chemical_list: D000911:Antibodies, Monoclonal; D000511:alpha-Macroglobulins; C024668:plasmin-alpha(2)-macroglobulin complex; D010958:Plasminogen; D005341:Fibrinolysin; D003894:Deamino Arginine Vasopressin