ORIGINAL ARTICLESCarbon monoxide-releasing molecule-2 decreases fibrinolysis in human plasmaNielsen, Vance Ga,b; Kirklin, James Kb; George, James FbAuthor Information aDepartment of Anesthesiology, USA bDepartment of Surgery, The University of Alabama at Birmingham, Birmingham, Alabama, USA Received 8 March, 2009 Revised 19 May, 2009 Accepted 6 June, 2009 Correspondence to Vance G. Nielsen, MD, Department of Anesthesiology, 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: email@example.com Blood Coagulation & Fibrinolysis: September 2009 - Volume 20 - Issue 6 - p 448-455 doi: 10.1097/MBC.0b013e32832f4335 Buy Metrics Abstract Carbon monoxide, derived from carbon monoxide-releasing molecules, has been recently demonstrated to enhance the velocity of formation and strength of plasma thrombi. We tested the hypothesis that carbon monoxide-releasing molecule-2 would modulate fibrinolysis of plasma thrombi. Normal plasma was exposed to 0, 25, 50, 100 or 200 μmol/l carbon monoxide-releasing molecule-2, with coagulation activated with tissue factor and fibrinolysis initiated with tissue-type plasminogen activator. Additional experiments utilized factor XIII, plasminogen activator inhibitor-1, thrombin activatable fibrinolysis inhibitor or α2-antiplasmin-deficient plasmas. Thrombus growth/disintegration kinetics was monitored with thrombelastography. Carbon monoxide-releasing molecule-2, in a concentration-dependent fashion, increased the velocity of thrombus formation and strength, and markedly attenuated fibrinolysis in normal plasma. In factor XIII-deficient plasma, carbon monoxide-releasing molecule-2 mediated effects on thrombus growth/disintegration kinetics were similar to that seen with normal plasma; however, carbon monoxide-releasing molecule-2 had a less marked effect on thrombus growth/disintegration in both plasminogen activator inhibitor-1 and thrombin activatable fibrinolysis inhibitor-deficient plasma, with even less carbon monoxide-releasing molecule-2-mediated effects noted in α2-antiplasmin-deficient plasma. Carbon monoxide-releasing molecule-2 attenuated fibrinolysis by enhancing the velocity of clot growth and strength while augmenting the effects of plasminogen activator inhibitor-1, thrombin activatable fibrinolysis inhibitor and α2-antiplasmin. These findings serve as the rationale for further investigations to determine if carbon monoxide-releasing molecules could be utilized as hemostatic agents. © 2009 Lippincott Williams & Wilkins, Inc.