Carbon Monoxide Releasing Molecule-2 Enhances Coagulation and Diminishes Fibrinolytic Vulnerability in Subjects Exposed to Warfarin

Vance G Nielsen, Ejaz S. Khan, James K. Kirklin, James F. George

Research output: Contribution to journalArticle

12 Citations (Scopus)

Abstract

Introduction: 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 obtained from warfarin-treated subjects would demonstrate improved coagulation and decreased fibrinolytic vulnerability following exposure to CORM-2. Materials and Methods: Anonymous donor plasma samples with international normalized ratios (INR) values ranging from 1.5-5.4 were exposed to 0 or 100 μM CORM-2 and activated with tissue factor (12 samples). Additional samples within the same INR range were exposed to 0 or 100 μM CORM-2 and 0 or 100 U/ml tissue-type plasminogen activator (tPA) to assess fibrinolytic vulnerability (8 samples). Thrombelastographic data were collected until either clot strength stabilized or clot lysis occurred as appropriate. Results and Conclusions: In the absence of tPA, all but one sample (INR=1.5) demonstrated a marked increase in the velocity of clot formation (40-577%) and strength (42-180%) following CORM-2 exposure. Of interest, in the presence of tPA, all samples (including the previously unresponsive sample) were noted to have an increase in the velocity of clot formation and strength, coupled with a prolonged onset to maximal rate of clot lysis (60-242%) and increased clot lysis time (74-149%). As with normal and hemophilic plasma, both enhancement of coagulation and attenuation of fibrinolysis occur following CORM-2 exposure in plasma from warfarin-treated subjects. Future investigation must determine if carbon monoxide releasing molecules could be used therapeutically to control bleeding in warfarin-treated patients.

Original languageEnglish (US)
Pages (from-to)68-73
Number of pages6
JournalThrombosis Research
Volume126
Issue number1
DOIs
StatePublished - Jul 2010
Externally publishedYes

Fingerprint

Warfarin
Carbon Monoxide
International Normalized Ratio
Plasminogen Activators
Fibrinolysis
Fibrin Clot Lysis Time
Thromboplastin
Tissue Plasminogen Activator
tricarbonyldichlororuthenium (II) dimer
Tissue Donors
Hemorrhage

Keywords

  • Carbon monoxide releasing molecule
  • International Normalized Ratio
  • Thrombelastography
  • Warfarin

ASJC Scopus subject areas

  • Hematology
  • Medicine(all)

Cite this

Carbon Monoxide Releasing Molecule-2 Enhances Coagulation and Diminishes Fibrinolytic Vulnerability in Subjects Exposed to Warfarin. / Nielsen, Vance G; Khan, Ejaz S.; Kirklin, James K.; George, James F.

In: Thrombosis Research, Vol. 126, No. 1, 07.2010, p. 68-73.

Research output: Contribution to journalArticle

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abstract = "Introduction: 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 obtained from warfarin-treated subjects would demonstrate improved coagulation and decreased fibrinolytic vulnerability following exposure to CORM-2. Materials and Methods: Anonymous donor plasma samples with international normalized ratios (INR) values ranging from 1.5-5.4 were exposed to 0 or 100 μM CORM-2 and activated with tissue factor (12 samples). Additional samples within the same INR range were exposed to 0 or 100 μM CORM-2 and 0 or 100 U/ml tissue-type plasminogen activator (tPA) to assess fibrinolytic vulnerability (8 samples). Thrombelastographic data were collected until either clot strength stabilized or clot lysis occurred as appropriate. Results and Conclusions: In the absence of tPA, all but one sample (INR=1.5) demonstrated a marked increase in the velocity of clot formation (40-577{\%}) and strength (42-180{\%}) following CORM-2 exposure. Of interest, in the presence of tPA, all samples (including the previously unresponsive sample) were noted to have an increase in the velocity of clot formation and strength, coupled with a prolonged onset to maximal rate of clot lysis (60-242{\%}) and increased clot lysis time (74-149{\%}). As with normal and hemophilic plasma, both enhancement of coagulation and attenuation of fibrinolysis occur following CORM-2 exposure in plasma from warfarin-treated subjects. Future investigation must determine if carbon monoxide releasing molecules could be used therapeutically to control bleeding in warfarin-treated patients.",
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AB - Introduction: 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 obtained from warfarin-treated subjects would demonstrate improved coagulation and decreased fibrinolytic vulnerability following exposure to CORM-2. Materials and Methods: Anonymous donor plasma samples with international normalized ratios (INR) values ranging from 1.5-5.4 were exposed to 0 or 100 μM CORM-2 and activated with tissue factor (12 samples). Additional samples within the same INR range were exposed to 0 or 100 μM CORM-2 and 0 or 100 U/ml tissue-type plasminogen activator (tPA) to assess fibrinolytic vulnerability (8 samples). Thrombelastographic data were collected until either clot strength stabilized or clot lysis occurred as appropriate. Results and Conclusions: In the absence of tPA, all but one sample (INR=1.5) demonstrated a marked increase in the velocity of clot formation (40-577%) and strength (42-180%) following CORM-2 exposure. Of interest, in the presence of tPA, all samples (including the previously unresponsive sample) were noted to have an increase in the velocity of clot formation and strength, coupled with a prolonged onset to maximal rate of clot lysis (60-242%) and increased clot lysis time (74-149%). As with normal and hemophilic plasma, both enhancement of coagulation and attenuation of fibrinolysis occur following CORM-2 exposure in plasma from warfarin-treated subjects. Future investigation must determine if carbon monoxide releasing molecules could be used therapeutically to control bleeding in warfarin-treated patients.

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