ORIGINAL ARTICLESThe antifibrinolytic effects of carbon monoxide-releasing molecule-2 are fibrin and α2-antiplasmin dependentNielsen, Vance GAuthor Information Department of Anesthesiology, Drexel University College of Medicine, Philadelphia, Pennsylvania, USA Received 25 March, 2010 Revised 18 May, 2010 Accepted 5 June, 2010 Correspondence to Vance G. Nielsen, MD, Hahnemann University Hospital, Drexel University College of Medicine, Broad & Vine Streets, Mail Stop 310, Philadelphia, PA 19102, USA Tel: +1 215 762 8936; fax: +1 215 762 8656; e-mail: firstname.lastname@example.org Blood Coagulation & Fibrinolysis: September 2010 - Volume 21 - Issue 6 - p 584-587 doi: 10.1097/MBC.0b013e32833cea13 Buy Metrics Abstract Carbon monoxide derived from a carbon monoxide-releasing molecule [tricarbonyldichlororuthenium (II) dimer; CORM-2] has been recently demonstrated to diminish tissue-type plasminogen activator (tPA)-mediated fibrinolysis of plasma thrombi via enhancement of α2-antiplasmin–plasmin interactions. The goal of this study was to confirm this mechanism by comparing tPA-mediated fibrinolysis with fibrin-independent, α2-antiplasmin-resistant streptokinase-mediated fibrinolysis in CORM-2 exposed plasma. Normal plasma was exposed to 0 or 100 μmol/l CORM-2, with coagulation activated with tissue factor and fibrinolysis initiated with 100 U/ml tPA or 50 U/ml streptokinase. Thrombus growth/disintegration kinetics were monitored with thrombelastography until clot lysis time occurred. Unlike tPA-lysed clots, streptokinase-exposed thrombi demonstrated no significant CORM-2-mediated prolongation of clot growth time or clot lysis time. In contrast, streptokinase-mediated lysis did not significantly change the CORM-2-mediated percentage increase in the maximum rate of clot growth or maximum rate of clot lysis compared with tPA-exposed thrombi. CORM-2 likely attenuates fibrinolysis by a fibrin-dependent/α2-antiplasmin-dependent mechanism. Additional molecular investigation (e.g., mass spectroscopy) is planned to further elucidate how CORM-2 modifies fibrinogen/fibrin. © 2010 Lippincott Williams & Wilkins, Inc.