Coagulation and the fibrin network in rheumatic disease: a role beyond haemostasis

Nat Rev Rheumatol. 2012 Dec;8(12):738-46. doi: 10.1038/nrrheum.2012.184. Epub 2012 Nov 13.

Abstract

Activation of the immune system has been increasingly recognised to be associated with procoagulatory status in patients with inflammatory rheumatic disease. Changes in endothelial cell and platelet activation, blood flow, expression and activity of different coagulation factors, and impaired fibrinolysis serve as pathophysiological basis for enhanced risk of venous thromboembolism in inflammatory rheumatic diseases, such as rheumatoid arthritis (RA), connective tissue diseases and vasculitides. Recent studies identifying mechanisms for a functional role of coagulation factors beyond haemostasis have provided examples of interesting links between the coagulation system and innate immune activation. Furthermore, citrullinated fibrinogen is an important and early autoantigen in patients with RA carrying the HLA-DRβ1 shared epitope allele, which demonstrates an adaptive immune response to a coagulation factor in an inflammatory rheumatic disease. Additional studies have provided strong evidence that a multitude of different components of the haemostatic system (such as thrombin, fibrinogen, coagulation factor XIII and factors of the fibrinolytic system) are relevant mediators of inflammatory processes as well as of inflammatory control. Understanding the interactions between coagulation and the immune system in inflammatory rheumatic diseases will not only improve our knowledge of disease mechanisms, but could also permit the development of innovative therapeutic interventions.

Publication types

  • Review

MeSH terms

  • Blood Coagulation / physiology*
  • Endothelium, Vascular / physiology
  • Female
  • Fibrin / metabolism
  • Hemostasis / physiology*
  • Humans
  • Immunity, Innate / physiology*
  • Male
  • Platelet Activation / physiology
  • Rheumatic Diseases / complications
  • Rheumatic Diseases / immunology
  • Rheumatic Diseases / physiopathology*
  • Venous Thromboembolism / etiology
  • Venous Thromboembolism / immunology
  • Venous Thromboembolism / physiopathology*

Substances

  • Fibrin