The procoagulant properties of purified fibrinogen concentrate are enhanced by carbon monoxide releasing molecule-2

Kelly A. MacHovec, Deepu S. Ushakumari, Ian J. Welsby, Vance G Nielsen

Research output: Contribution to journalArticle

11 Citations (Scopus)

Abstract

Introduction: Fibrinogen concentrate has been demonstrated to enhance coagulation in vitro and in several clinical settings of coagulopathy. We have recently demonstrated that carbon monoxide releasing molecule-2 (tricarbonyldichlororuthenium (II) dimer; CORM-2) enhances fibrinogen as a substrate for thrombin via an attached heme. The objective of this study was to determine if CORM-2 modified fibrinogen concentrate would enhance coagulation more effectively than CORM-2 naïve fibrinogen concentrate. Materials and Methods: In the first series of experiments, fibrinogen concentrate (final concentration 300 mg/dl) was exposed to 0, 50 or 100 μM CORM-2 for 5 min at 37 °C prior to being added to citrated, fibrinogen depleted plasma. In another series of experiments, citrated plasma obtained from 12 normal subjects was 50% diluted with crystalloid to which was added fibrinogen concentrate (final concentration 300 mg/dl) exposed to 0 or 100 μM CORM-2. Coagulation was activated with tissue factor (n = 8 per condition). Thrombus growth was monitored with thrombelastography for 15 min. Results and Conclusions: CORM-2 modification of fibrinogen concentrate significantly enhanced the velocity of clot formation (30-50%) and strength (15-31%) in fibrinogen deficient plasma. Similarly, while diluted plasma-derived thrombi demonstrated a marked decrease in velocity of formation (54%) and strength (61%), fibrinogen concentrate significantly enhanced velocity (217%) and strength (171%); however, CORM-2 modified fibrinogen concentrate significantly increased velocity (303%) and strength (205%) to a greater extent. Additional in vitro investigation and in vivo preclinical assessments of the hemostatic efficacy of CORM-2 modified fibrinogen concentrate are warranted.

Original languageEnglish (US)
Pages (from-to)793-796
Number of pages4
JournalThrombosis Research
Volume129
Issue number6
DOIs
StatePublished - Jun 2012
Externally publishedYes

Fingerprint

Carbon Monoxide
Fibrinogen
Thrombosis
Thrombelastography
tricarbonyldichlororuthenium (II) dimer
Thromboplastin
Hemostatics
Heme
Thrombin

Keywords

  • Carbon monoxide releasing molecule
  • Fibrinogen concentrate
  • Hemodilution
  • Thrombelastography

ASJC Scopus subject areas

  • Hematology

Cite this

The procoagulant properties of purified fibrinogen concentrate are enhanced by carbon monoxide releasing molecule-2. / MacHovec, Kelly A.; Ushakumari, Deepu S.; Welsby, Ian J.; Nielsen, Vance G.

In: Thrombosis Research, Vol. 129, No. 6, 06.2012, p. 793-796.

Research output: Contribution to journalArticle

MacHovec, Kelly A. ; Ushakumari, Deepu S. ; Welsby, Ian J. ; Nielsen, Vance G. / The procoagulant properties of purified fibrinogen concentrate are enhanced by carbon monoxide releasing molecule-2. In: Thrombosis Research. 2012 ; Vol. 129, No. 6. pp. 793-796.
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abstract = "Introduction: Fibrinogen concentrate has been demonstrated to enhance coagulation in vitro and in several clinical settings of coagulopathy. We have recently demonstrated that carbon monoxide releasing molecule-2 (tricarbonyldichlororuthenium (II) dimer; CORM-2) enhances fibrinogen as a substrate for thrombin via an attached heme. The objective of this study was to determine if CORM-2 modified fibrinogen concentrate would enhance coagulation more effectively than CORM-2 na{\"i}ve fibrinogen concentrate. Materials and Methods: In the first series of experiments, fibrinogen concentrate (final concentration 300 mg/dl) was exposed to 0, 50 or 100 μM CORM-2 for 5 min at 37 °C prior to being added to citrated, fibrinogen depleted plasma. In another series of experiments, citrated plasma obtained from 12 normal subjects was 50{\%} diluted with crystalloid to which was added fibrinogen concentrate (final concentration 300 mg/dl) exposed to 0 or 100 μM CORM-2. Coagulation was activated with tissue factor (n = 8 per condition). Thrombus growth was monitored with thrombelastography for 15 min. Results and Conclusions: CORM-2 modification of fibrinogen concentrate significantly enhanced the velocity of clot formation (30-50{\%}) and strength (15-31{\%}) in fibrinogen deficient plasma. Similarly, while diluted plasma-derived thrombi demonstrated a marked decrease in velocity of formation (54{\%}) and strength (61{\%}), fibrinogen concentrate significantly enhanced velocity (217{\%}) and strength (171{\%}); however, CORM-2 modified fibrinogen concentrate significantly increased velocity (303{\%}) and strength (205{\%}) to a greater extent. Additional in vitro investigation and in vivo preclinical assessments of the hemostatic efficacy of CORM-2 modified fibrinogen concentrate are warranted.",
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AU - Nielsen, Vance G

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N2 - Introduction: Fibrinogen concentrate has been demonstrated to enhance coagulation in vitro and in several clinical settings of coagulopathy. We have recently demonstrated that carbon monoxide releasing molecule-2 (tricarbonyldichlororuthenium (II) dimer; CORM-2) enhances fibrinogen as a substrate for thrombin via an attached heme. The objective of this study was to determine if CORM-2 modified fibrinogen concentrate would enhance coagulation more effectively than CORM-2 naïve fibrinogen concentrate. Materials and Methods: In the first series of experiments, fibrinogen concentrate (final concentration 300 mg/dl) was exposed to 0, 50 or 100 μM CORM-2 for 5 min at 37 °C prior to being added to citrated, fibrinogen depleted plasma. In another series of experiments, citrated plasma obtained from 12 normal subjects was 50% diluted with crystalloid to which was added fibrinogen concentrate (final concentration 300 mg/dl) exposed to 0 or 100 μM CORM-2. Coagulation was activated with tissue factor (n = 8 per condition). Thrombus growth was monitored with thrombelastography for 15 min. Results and Conclusions: CORM-2 modification of fibrinogen concentrate significantly enhanced the velocity of clot formation (30-50%) and strength (15-31%) in fibrinogen deficient plasma. Similarly, while diluted plasma-derived thrombi demonstrated a marked decrease in velocity of formation (54%) and strength (61%), fibrinogen concentrate significantly enhanced velocity (217%) and strength (171%); however, CORM-2 modified fibrinogen concentrate significantly increased velocity (303%) and strength (205%) to a greater extent. Additional in vitro investigation and in vivo preclinical assessments of the hemostatic efficacy of CORM-2 modified fibrinogen concentrate are warranted.

AB - Introduction: Fibrinogen concentrate has been demonstrated to enhance coagulation in vitro and in several clinical settings of coagulopathy. We have recently demonstrated that carbon monoxide releasing molecule-2 (tricarbonyldichlororuthenium (II) dimer; CORM-2) enhances fibrinogen as a substrate for thrombin via an attached heme. The objective of this study was to determine if CORM-2 modified fibrinogen concentrate would enhance coagulation more effectively than CORM-2 naïve fibrinogen concentrate. Materials and Methods: In the first series of experiments, fibrinogen concentrate (final concentration 300 mg/dl) was exposed to 0, 50 or 100 μM CORM-2 for 5 min at 37 °C prior to being added to citrated, fibrinogen depleted plasma. In another series of experiments, citrated plasma obtained from 12 normal subjects was 50% diluted with crystalloid to which was added fibrinogen concentrate (final concentration 300 mg/dl) exposed to 0 or 100 μM CORM-2. Coagulation was activated with tissue factor (n = 8 per condition). Thrombus growth was monitored with thrombelastography for 15 min. Results and Conclusions: CORM-2 modification of fibrinogen concentrate significantly enhanced the velocity of clot formation (30-50%) and strength (15-31%) in fibrinogen deficient plasma. Similarly, while diluted plasma-derived thrombi demonstrated a marked decrease in velocity of formation (54%) and strength (61%), fibrinogen concentrate significantly enhanced velocity (217%) and strength (171%); however, CORM-2 modified fibrinogen concentrate significantly increased velocity (303%) and strength (205%) to a greater extent. Additional in vitro investigation and in vivo preclinical assessments of the hemostatic efficacy of CORM-2 modified fibrinogen concentrate are warranted.

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