Iron and carbon monoxide enhance coagulation and attenuate fibrinolysis by different mechanisms

Vance G. Nielsen, Etheresia Pretorius

Research output: Contribution to journalArticlepeer-review

39 Scopus citations

Abstract

Two parallel lines of investigation elucidating novel mechanisms by which iron (scanning electron microscopybased) and carbon monoxide (viscoelastic-based) enhance coagulation and diminish fibrinolysis have emerged over the past few years. However, a multimodal approach to ascertain the effects of iron and carbon monoxide remained to be performed. Such investigation could be important, as iron and carbon monoxide are two of the products of heme catabolism via heme oxygenase-1, an enzyme upregulated in a variety of disease states associated with thrombophilia. Human plasma was exposed to ferric chloride, carbon monoxide derived from carbon monoxide-releasing molecule-2, or their combination. Viscoelastic studies demonstrated ferric chloride and carbon monoxide mediated enhancement of velocity of growth, and final clot strength, with the combination of the two molecules noted to have all the prothrombotic kinetic effects of either separately. Parallel ultrastructural studies demonstrated separate types of fibrin polymer cross-linking and matting in plasma exposed to ferric chloride and carbon monoxide, with the combination sharing features of each molecule. In conclusion, we present the first evidence that iron and carbon monoxide interact with key coagulation and fibrinolytic processes, resulting in thrombi that begin to form more quickly, grow faster, become stronger, and are more resistant to lysis.

Original languageEnglish (US)
Pages (from-to)695-702
Number of pages8
JournalBlood Coagulation and Fibrinolysis
Volume25
Issue number7
DOIs
StatePublished - 2014

Keywords

  • Carbon monoxide
  • Coagulation
  • Fibrinogen
  • Fibrinolysis
  • Iron

ASJC Scopus subject areas

  • Hematology

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