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Redox-based thrombelastographic method to detect carboxyhemefibrinogen-mediated hypercoagulability
Journal article   Peer reviewed

Redox-based thrombelastographic method to detect carboxyhemefibrinogen-mediated hypercoagulability

Vance G. Nielsen, Matthew R. Arkebauer and Keith Vosseller
Blood coagulation & fibrinolysis, v 22(8), pp 657-661
01 Dec 2011
DOI: https://doi.org/10.1097/MBC.0b013e32834aa7b0
PMID: 21822126
Featured in Collection :   UN Sustainable Development Goals @ Drexel

Abstract

Hematology Life Sciences & Biomedicine Science & Technology
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 mu mol/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+2 to Fe+3 in heme. Addition of calcium and tissue factor activation in disposable thrombelastographic cups was performed, followed by data collection at 37 degrees C for 15 min. Elastic modulus (G, dynes/cm(2)) 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+2 to Fe+3 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. Blood Coagul Fibrinolysis 22:657-661 (C) 2011 Wolters Kluwer Health vertical bar Lippincott Williams & Wilkins.

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Hematology
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