Plasminogen Activation In Vivo upon Intravenous Infusion of DDAVP

Marcel Levi; Jan Paul de Boer; Dorina Roem; Jan Wouter ten Cate; C Erik Hack

doi:10.1055/s-0038-1648390

Thrombosis and Haemostasis, Table of Contents

Thromb Haemost 1992; 67(01): 111-116
DOI: 10.1055/s-0038-1648390

Original Articles

Schattauer GmbH Stuttgart

Plasminogen Activation In Vivo upon Intravenous Infusion of DDAVP

Quantitative Assessment of Plasmin-α₂-Antiplasmin Complex with a Novel Monoclonal Antibody Based Radioimmunoassay

Marcel Levi

¹The Center for Thrombosis, Haemostasis and Atherosclerosis Research, Academic Medical Center, Amsterdam, The Netherlands

,

Jan Paul de Boer

²Dept. of Autoimmune Diseases, Central Laboratory of the Netherlands Red Cross Bloodtransfusion Service and Laboratory for Clinical and Experimental Immunology, University of Amsterdam, Amsterdam, The Netherlands

,

Dorina Roem

²Dept. of Autoimmune Diseases, Central Laboratory of the Netherlands Red Cross Bloodtransfusion Service and Laboratory for Clinical and Experimental Immunology, University of Amsterdam, Amsterdam, The Netherlands

,

Jan Wouter ten Cate

¹The Center for Thrombosis, Haemostasis and Atherosclerosis Research, Academic Medical Center, Amsterdam, The Netherlands

,

C Erik Hack

²Dept. of Autoimmune Diseases, Central Laboratory of the Netherlands Red Cross Bloodtransfusion Service and Laboratory for Clinical and Experimental Immunology, University of Amsterdam, Amsterdam, The Netherlands

› Author Affiliations

Abstract

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Summary

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 α₂ antiplasmin (PAP complex) was developed using monoclonal antibodies preferentially reacting with complexed and inactivated α₂-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.

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References

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