Thrombin-Fibrin(ogen) Interactions, Host Defense and Risk of Thrombosis

Anne-Marije Hulshof*, H Coenraad Hemker, Henri M H Spronk, Yvonne M C Henskens, Hugo Ten Cate*

*Corresponding author for this work

Research output: Contribution to journal(Systematic) Review article peer-review

3 Citations (Web of Science)

Abstract

Fibrinogen is a well-known risk factor for arterial and venous thrombosis. Its function is not restricted to clot formation, however, as it partakes in a complex interplay between thrombin, soluble plasma fibrinogen, and deposited fibrin matrices. Fibrinogen, like thrombin, participates predominantly in hemostasis to maintain vascular integrity, but executes some important pleiotropic effects: firstly, as observed in thrombin generation experiments, fibrin removes thrombin from free solution by adsorption. The adsorbed thrombin is protected from antithrombins, notably α2-macroglobulin, and remains physiologically active as it can activate factors V, VIII, and platelets. Secondly, immobilized fibrinogen or fibrin matrices activate monocytes/macrophages and neutrophils via Mac-1 interactions. Immobilized fibrin(ogen) thereby elicits a pro-inflammatory response with a reciprocal stimulating effect of the immune system on coagulation. In contrast, soluble fibrinogen prohibits recruitment of these immune cells. Thus, while fibrin matrices elicit a procoagulant response, both directly by protecting thrombin and indirectly through the immune system, high soluble fibrinogen levels might protect patients due to its immune diminutive function. The in vivo influence of the 'protective' plasma fibrinogen versus the 'pro-thrombotic' fibrin matrices on thrombosis should be explored in future research.

Original languageEnglish
Article number2590
Number of pages15
JournalInternational journal of molecular sciences
Volume22
Issue number5
DOIs
Publication statusPublished - 4 Mar 2021

Keywords

  • Animals
  • Fibrin/metabolism
  • Fibrinogen/metabolism
  • Hemostasis/physiology
  • Humans
  • Immune System/metabolism
  • Thrombin/metabolism
  • Thrombosis/metabolism
  • thrombin
  • fibrinogen
  • inflammatory disease
  • thrombin generation assay
  • immune system

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