Cell-derived microparticles in synovial fluid from inflamed arthritic joints support coagulation exclusively via a factor VII-dependent mechanism

Arthritis Rheum. 2002 Nov;46(11):2857-66. doi: 10.1002/art.10587.


Objective: To determine the cellular origin of synovial microparticles, their procoagulant properties, and their relationship to local hypercoagulation.

Methods: Microparticles in synovial fluid and plasma from patients with rheumatoid arthritis (RA; n = 10) and patients with other forms of arthritis (non-RA; n = 10) and in plasma from healthy subjects (n = 20) were isolated by centrifugation. Microparticles were identified by flow cytometry. The ability of microparticles to support coagulation was determined in normal plasma. Concentrations of prothrombin fragment F(1+2) (by enzyme-linked immunosorbent assay [ELISA]) and thrombin-antithrombin (TAT) complexes (by ELISA) were determined as estimates of the coagulation activation status in vivo.

Results: Plasma from patients and healthy controls contained comparable numbers of microparticles, which originated from platelets and erythrocytes. Synovial microparticles from RA patients and non-RA patients originated mainly from monocytes and granulocytes; few originated from platelets and erythrocytes. Synovial microparticles bound less annexin V (which binds to negatively charged phospholipids) than did plasma microparticles, exposed tissue factor, and supported thrombin generation via factor VII. F(1+2) (median 66 nM) and TAT complex (median 710 microg/liter) concentrations were elevated in synovial fluid compared with plasma from the patients (1.6 nM and 7.0 microg/liter, respectively) as well as the controls (1.0 nM and 2.9 microg/liter, respectively).

Conclusion: Synovial fluid contains high numbers of microparticles derived from leukocytes that are strongly coagulant via the factor VII-dependent pathway. We propose that these microparticles contribute to the local hypercoagulation and fibrin deposition in inflamed joints of patients with RA and other arthritic disorders.

MeSH terms

  • Adult
  • Aged
  • Arthritis / metabolism*
  • Arthritis, Rheumatoid / metabolism
  • Blood Coagulation / physiology*
  • Factor VII / physiology*
  • Female
  • Flow Cytometry
  • Humans
  • Male
  • Middle Aged
  • Phospholipids
  • Synovial Fluid / chemistry*
  • Thrombin / analysis


  • Phospholipids
  • Factor VII
  • Thrombin