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Carbon monoxide-releasing molecule-2 decreases fibrinolysis in human plasma
Journal article   Peer reviewed

Carbon monoxide-releasing molecule-2 decreases fibrinolysis in human plasma

Vance G Nielsen, James K Kirklin and James F George
Blood coagulation & fibrinolysis, v 20(6), pp 448-455
Sep 2009
PMID: 19581800

Abstract

alpha-2-Antiplasmin - pharmacology Blood Coagulation - drug effects Carbon Monoxide - pharmacology Carboxypeptidase B2 - pharmacology Dose-Response Relationship, Drug Drug Evaluation, Preclinical Factor XIII - pharmacology Fibrinogen - analysis Fibrinolysis - drug effects Hemostatics - administration & dosage Hemostatics - pharmacology Humans Organometallic Compounds - administration & dosage Organometallic Compounds - pharmacology Partial Thromboplastin Time Plasminogen Activator Inhibitor 1 - pharmacology Prothrombin Time Thrombelastography Thromboplastin - pharmacology Tissue Plasminogen Activator - pharmacology
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 micromol/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 alpha2-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 alpha2-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 alpha2-antiplasmin. These findings serve as the rationale for further investigations to determine if carbon monoxide-releasing molecules could be utilized as hemostatic agents.

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Collaboration types
Domestic collaboration
Web of Science research areas
Hematology
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