Cell-derived microparticles in synovial fluid from inflamed arthritic joints support coagulation exclusively via a factor VII–dependent mechanism
Version of Record online: 8 NOV 2002
Copyright © 2002 by the American College of Rheumatology
Arthritis & Rheumatism
Volume 46, Issue 11, pages 2857–2866, November 2002
How to Cite
Berckmans, R. J., Nieuwland, R., Tak, P. P., Böing, A. N., Romijn, F. P. H. T. M., Kraan, M. C., Breedveld, F. C., Hack, C. E. and Sturk, A. (2002), Cell-derived microparticles in synovial fluid from inflamed arthritic joints support coagulation exclusively via a factor VII–dependent mechanism. Arthritis & Rheumatism, 46: 2857–2866. doi: 10.1002/art.10587
- Issue online: 8 NOV 2002
- Version of Record online: 8 NOV 2002
- Manuscript Accepted: 15 JUL 2002
- Manuscript Received: 21 MAY 2001
To determine the cellular origin of synovial microparticles, their procoagulant properties, and their relationship to local hypercoagulation.
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 F1+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.
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. F1+2 (median 66 nM) and TAT complex (median 710 μg/liter) concentrations were elevated in synovial fluid compared with plasma from the patients (1.6 nM and 7.0 μg/liter, respectively) as well as the controls (1.0 nM and 2.9 μg/liter, respectively).
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.