title: Cell-derived microparticles in synovial fluid from inflamed arthritic joints support coagulation exclusively via a factor VII-dependent mechanism.
abstract: 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).
  
  
  CONCLUSIONS
  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.
authors.affiliation: Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands. r.j.berckmans@amc.uva.nl
authors.forename: René J
authors.initials: RJ
authors.lastname: Berckmans
authors.forename: Rienk
authors.initials: R
authors.lastname: Nieuwland
authors.forename: Paul Peter
authors.initials: PP
authors.lastname: Tak
authors.forename: Anita N
authors.initials: AN
authors.lastname: Böing
authors.forename: Fred P H T M
authors.initials: FP
authors.lastname: Romijn
authors.forename: Maarten C
authors.initials: MC
authors.lastname: Kraan
authors.forename: Ferdinand C
authors.initials: FC
authors.lastname: Breedveld
authors.forename: C Erik
authors.initials: CE
authors.lastname: Hack
authors.forename: Augueste
authors.initials: A
authors.lastname: Sturk
mesh_terms: D000328:Adult; D000368:Aged; D001168:Arthritis / Q000378:metabolism*; D001172:Arthritis, Rheumatoid / Q000378:metabolism; D001777:Blood Coagulation / Q000502:physiology*; D005167:Factor VII / Q000502:physiology*; D005260:Female; D005434:Flow Cytometry; D006801:Humans; D008297:Male; D008875:Middle Aged; D010743:Phospholipids; D013582:Synovial Fluid / Q000737:chemistry*; D013917:Thrombin / Q000032:analysis
chemical_list: D010743:Phospholipids; D005167:Factor VII; D013917:Thrombin