The antifibrinolytic effects of carbon monoxide-releasing molecule-2 are fibrin and α2-antiplasmin dependent

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9 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)584-587
Number of pages4
JournalBlood Coagulation and Fibrinolysis
Volume21
Issue number6
DOIs
StatePublished - Sep 1 2010
Externally publishedYes

Keywords

  • carbon monoxide-releasing molecule
  • fibrinolysis
  • streptokinase
  • thrombelastography
  • tissue-type plasminogen activator

ASJC Scopus subject areas

  • Hematology

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