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Anticoagulant Drugs: Low-Molecular-Weight Heparins01:30

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Hemostasis is a crucial process that prevents excessive blood loss from damaged blood vessels. It involves various mechanisms such as vasoconstriction, platelet adhesion and activation, and fibrin formation. The importance of each mechanism depends on the type of vessel injury. In contrast, thrombosis is the abnormal formation of a blood clot within the blood vessels, leading to potential complications if the clot obstructs blood flow. Thrombosis can be caused by increased coagulability of the...

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Redox-based thrombelastographic method to detect carboxyhemefibrinogen-mediated hypercoagulability.

Vance G Nielsen1, Matthew R Arkebauer, Keith Vosseller

  • 1Department of Anesthesiology, Drexel University College of Medicine, Philadelphia, Pennsylvania, USA. vance.nielsen@drexelmed.edu

Blood Coagulation & Fibrinolysis : an International Journal in Haemostasis and Thrombosis
|August 9, 2011
PubMed
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Carbon monoxide in cigarette smoke increases blood clot strength by forming carboxyhemefibrinogen. A new redox method using phenylhydroxylamine (PHA) can reverse this effect, suggesting a way to measure smoking-induced hypercoagulability.

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Area of Science:

  • Biochemistry
  • Hematology
  • Toxicology

Background:

  • Cigarette smoking is linked to hypercoagulability, a state of increased blood clotting.
  • Carbon monoxide (CO) from smoking enhances coagulation by binding to heme in fibrinogen.
  • The resulting carboxyhemefibrinogen's role in hypercoagulability requires further investigation.

Purpose of the Study:

  • To develop and validate a redox-based assay for detecting carboxyhemefibrinogen.
  • To investigate the impact of CO on plasma coagulation and its modulation by a reductant.
  • To establish a mechanistic link between carboxyhemefibrinogen and in-vitro hypercoagulability.

Main Methods:

  • Pooled plasma was treated with a CO-releasing molecule (CORM-2) and/or phenylhydroxylamine (PHA).
  • PHA converts heme iron from Fe(+2) to Fe(+3), oxidizing carboxyhemefibrinogen to methemefibrinogen.
  • Thrombelastography measured clot strength (elastic modulus, G) after calcium and tissue factor activation.

Main Results:

  • CORM-2 significantly increased plasma clot strength (G) by 67.8%.
  • PHA pretreatment significantly reduced CORM-2-induced increases in G.
  • Conversion to methemefibrinogen alone decreased G, and PHA abrogated CO-mediated hypercoagulability.

Conclusions:

  • A redox-based method effectively detects carboxyhemefibrinogen formation.
  • Conversion of carboxyhemefibrinogen to methemefibrinogen reverses CO-induced hypercoagulability.
  • This assay could mechanistically link smoking, carboxyhemefibrinogen, and hypercoagulability in clinical studies.