title: Arthritis is linked to local and systemic activation of coagulation and fibrinolysis pathways.
abstract: BACKGROUND
  Activation of coagulation and fibrinolysis play a role in the pathophysiology of experimental arthritis.
  
  
  OBJECTIVE
  To determine the extent of activation of the coagulation and fibrinolytic pathways in different joint diseases in humans and to ascertain the factors that may influence fibrin deposition within the joint.
  
  
  METHODS
  Plasma from normal subjects (controls, n= 21) and plasma and synovial fluid samples from patients with rheumatoid arthritis (RA; n = 64), osteoarthritis (OA; n = 29), spondyloarthropathy (SpA; n = 22) and crystal arthritis (CA; n = 25) were analyzed for the levels of TF (tissue factor) and tissue factor pathway inhibitor (TFPI) activities, thrombin-antithrombin III (TAT) complexes, and F1 + 2 (thrombin fragment), fibrin d-dimer and thrombin-activated fibrinolysis inhibitor (TAFI) antigenic levels. The measurements were analyzed by pairwise correlation with each other as well as with standard parameters of inflammation [C-reactive protein (CRP), joint leukocyte count]. Inter-group comparisons were performed to look for disease-specific differences.
  
  
  RESULTS
  Compared with healthy controls, patients with joint diseases had higher levels of TAT, F1 + 2 and d-dimers in their plasma. In the synovial fluid, TF activity, TAT, d-dimers, and TAFI were significantly higher in inflammatory arthritides than in OA. The levels were highest in RA patients. In the plasma, TF activity was correlated with TAT and d-dimer levels with CRP, TFPI, and TAT. In the synovial fluid, TF activity correlated with plasma CRP levels, synovial fluid leukocyte count, and synovial TAT and TAFI levels. In addition, synovial d-dimers correlated with CRP, and synovial TAFI levels were correlated with synovial F1 + 2 and TAT.
  
  
  CONCLUSIONS
  Activation of the coagulation and fibrinolytic cascades in the joint and in the circulation is evident in both inflammatory and degenerative joint diseases. Within the joint, inflammatory mechanisms leading to TF-mediated activation of the coagulation pathway and subsequent fibrin deposition is the most likely explanation for the observed findings. In the plasma, the link between inflammation (CRP increase) and TF activation is weak, and a non-TF-mediated mechanism of coagulation activation could explain these findings. RA is characterized by significantly higher levels of TAT in the synovial fluid and plasma than other arthritides. Although fibrinolytic activity is linked to inflammation, the increased amounts of TAFI in the joint, particularly in RA, may explain why fibrin formation is so prominent in this condition compared with other joint diseases.
authors.affiliation: Service of Rheumatology, University Hospital of Lausanne, Lausanne, Switzerland. aso@chuv.hospvd.ch
authors.forename: A K
authors.initials: AK
authors.lastname: So
authors.forename: P-A
authors.initials: PA
authors.lastname: Varisco
authors.forename: B
authors.initials: B
authors.lastname: Kemkes-Matthes
authors.forename: C
authors.initials: C
authors.lastname: Herkenne-Morard
authors.forename: V
authors.initials: V
authors.lastname: Chobaz-Péclat
authors.forename: J-C
authors.initials: JC
authors.lastname: Gerster
authors.forename: N
authors.initials: N
authors.lastname: Busso
mesh_terms: D000328:Adult; D000368:Aged; D001168:Arthritis / Q000209:etiology / Q000503:physiopathology*; D001172:Arthritis, Rheumatoid / Q000209:etiology / Q000503:physiopathology; D015415:Biomarkers / Q000032:analysis / Q000097:blood; D001777:Blood Coagulation / Q000502:physiology*; D025901:Carboxypeptidase B2 / Q000032:analysis; D016022:Case-Control Studies; D005260:Female; D005337:Fibrin / Q000378:metabolism; D005342:Fibrinolysis / Q000502:physiology*; D006801:Humans; D007249:Inflammation / Q000503:physiopathology; D016014:Linear Models; D008297:Male; D008875:Middle Aged; D010003:Osteoarthritis / Q000209:etiology / Q000503:physiopathology; D013167:Spondylitis, Ankylosing / Q000209:etiology / Q000503:physiopathology; D013582:Synovial Fluid / Q000737:chemistry
chemical_list: D015415:Biomarkers; D005337:Fibrin; D025901:Carboxypeptidase B2