Carbon monoxide releasing molecule-2 increases fibrinogen-dependent coagulation kinetics but does not enhance prothrombin activity

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

Research output: Contribution to journalArticle

20 Scopus citations

Abstract

We have previously determined that tricarbonyldichlororuthenium (II) dimer (CORM-2) increases plasma clot velocity of formation and strength by enhancing thrombin-fibrinogen interactions as determined by thrombelastography. The purpose of the present investigation was to further define the nature of CORM-2 interaction with prothrombin and fibrinogen by exposing purified proteins to CORM-2 or generating protein concentration-response curves in the absence or presence of CORM-2. Purified prothrombin was exposed to 0 or 100 μmol/l CORM-2 prior to being added to prothrombin-deficient plasma (n = 7-8 per condition). Fibrinogen-deficient plasma had fibrinogen added for a final concentration of 100-800 mg/dl and was exposed to 0 or 100 μmol/l CORM-2 (n = 4 per condition). Following tissue factor activation, thrombelastographic data were collected until clot strength stabilized. Exposure of prothrombin to CORM-2 did not significantly enhance coagulation kinetics. In sharp contrast, CORM-2 exposure enhanced fibrinogen coagulation kinetics in a concentration-dependent fashion, with peak effect seen at a fibrinogen concentration of 300 mg/dl that then progressively decreased throughout the range tested. Our data demonstrate that CORM-2 does not enhance plasma coagulation kinetics by modifying prothrombin; instead, the concept that CORM-2 modifies fibrinogen is the most likely explanation for the enhanced thrombin-fibrinogen interactions observed.

Original languageEnglish (US)
Pages (from-to)349-353
Number of pages5
JournalBlood Coagulation and Fibrinolysis
Volume21
Issue number4
DOIs
StatePublished - Jun 1 2010
Externally publishedYes

Keywords

  • Carbon monoxide releasing molecule
  • Fibrinogen
  • Prothrombin
  • Thrombelastography

ASJC Scopus subject areas

  • Hematology

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