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Carbon Monoxide Releasing Molecule-2 Enhances Coagulation and Diminishes Fibrinolytic Vulnerability in Plasma Exposed to Heparin or Argatroban
Journal article   Open access   Peer reviewed

Carbon Monoxide Releasing Molecule-2 Enhances Coagulation and Diminishes Fibrinolytic Vulnerability in Plasma Exposed to Heparin or Argatroban

Vance G. Nielsen, Ejaz S. Khan, James K. Kirklin and James F. George
Anesthesia and analgesia, v 111(6), pp 1347-1352
01 Dec 2010
PMID: 21048101
url
https://doi.org/10.1213/ane.0b013e3181fbc120View
Published, Version of Record (VoR)Maybe Open Access (Publisher Bronze) Open

Abstract

Anesthesiology Life Sciences & Biomedicine Science & Technology
BACKGROUND: It has been recently demonstrated that a carbon monoxide releasing molecule (tricarbonyldichlororuthenium [II] dimer; CORM-2) enhances coagulation and attenuates vulnerability to fibrinolysis in normal and hemophiliac human plasma. We tested the hypothesis that plasma anticoagulated with heparin or argatroban would demonstrate improved coagulation and decreased fibrinolytic vulnerability after exposure to CORM-2. METHODS: Normal plasma was anticoagulated with 0 to 0.1 mu g/mL unfractionated heparin or 0 to 1 mu g/mL argatroban. Samples were subsequently exposed to 0 or 100 mu M CORM-2 and activated with tissue factor. Additional samples with the same anticoagulant and CORM-2 exposure schema were incubated with 100 U/mL tissue-type plasminogen activator (tPA) to assess fibrinolytic vulnerability. Thrombelastographic data were collected until either clot strength stabilized or clot lysis occurred as appropriate. RESULTS: In the absence of tPA, CORM-2 significantly increased the velocity of clot growth in heparin (75%) and argatroban-exposed (40%) samples. Clot strength was also significantly increased in heparin (69%) and argatroban-exposed (72%) samples. In the presence of tPA, CORM-2-treated samples had even greater (94%-731%) increases in velocity of growth and strength after exposure to either anticoagulant and significantly increased clot lysis time (103%-200%). CONCLUSIONS: CORM-2 exposure resulted in faster-growing, stronger, longer-lived thrombi after anticoagulation with heparin or argatroban. Additional preclinical investigation is warranted to determine whether CORM-2 administration will be useful in attenuating bleeding complications associated with thromboprophylaxis.

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Collaboration types
Domestic collaboration
Web of Science research areas
Anesthesiology
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