Redox-based thrombelastographic method to detect carboxyhemefibrinogen- mediated hypercoagulability

Vance G. Nielsen, Matthew R. Arkebauer, Keith Vosseller

Research output: Contribution to journalArticle

34 Scopus citations

Abstract

Cigarette smoking is associated with plasmatic hypercoagulability, and carbon monoxide has been demonstrated to enhance coagulation by binding to a fibrinogen-bound heme. Our objective was to design and test a redox-based method to detect carboxyhemefibrinogen. Normal, pooled, citrated plasma was exposed to 0-100? μmol/l carbon monoxide releasing molecule-2 (tricarbonyldichlororuthenium (II) dimer; CORM-2) before or after exposure to the organic reductant phenylhydroxylamine (PHA, 0-30? mmol/l), a compound that rapidly converts Fe to Fe in heme. Addition of calcium and tissue factor activation in disposable thrombelastographic cups was performed, followed by data collection at 37°C for 15? min. Elastic modulus (G, dynes/cm) was the primary endpoint. CORM-2 significantly increased G values by 67.8% compared to unexposed plasma; pretreatment with 10? mmol/l PHA significantly decreased G values in CORM-2-exposed plasma by 77.1%, whereas 30? mmol/l PHA was required to significantly decrease G values by 64.0% in plasma following CORM-2 pre-exposure. G values were not significantly different between unexposed plasma and plasma exposed to CORM-2 followed by 30? mmol/l PHA addition. Conversion of fibrinogen-bound to the metheme state alone decreased G by 34.3-38.9% following exposure to 10-30? mmol/l PHA. Conversion of fibrinogen-bound heme Fe to Fe with PHA abrogated carbon monoxide-mediated increases in clot strength. Clinical trials are planned to investigate smoking individuals to mechanistically link carboxyhemefibrinogen formation with in-vitro hypercoagulability.

Original languageEnglish (US)
Pages (from-to)657-661
Number of pages5
JournalBlood Coagulation and Fibrinolysis
Volume22
Issue number8
DOIs
StatePublished - Dec 1 2011
Externally publishedYes

Keywords

  • Carbon monoxide releasing molecule
  • Fibrinogen
  • Heme
  • Hypercoagulability
  • Thrombelastography

ASJC Scopus subject areas

  • Hematology

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