Extravascular fibrin formation and dissolution in synovial tissue of patients with osteoarthritis and rheumatoid arthritis

Abstract

Fibrin deposition is a prominent finding in the synovium of patients with rheumatoid arthritis (RA). Macrophages are found in increased numbers in RA synovium, and these cells are known to produce a variety of procoagulant and anticoagulant molecules. Using immunohistologic techniques, the content and distribution of several important components of the coagulation system in the synovium of patients with RA, osteoarthritis (OA), or traumatic joint abnormalities requiring surgery were investigated. Samples from 3 patients from each category were examined in detail. RA synovium (compared with that of patients with OA or joint trauma) had increased numbers of macrophages and increased expression/content of fibrinogen, tissue factor, factor XIII, tissue transglutaminase, cross‐linked fibrin (fibrin D dimer), urokinase‐type plasminogen activator, and α2–plasmin inhibitor. Macrophage content in RA synovium was increased in both the lining cell areas and the interstitial cell areas. Fibrinogen was distributed throughout the tissue in all samples and was greater in RA synovium. In trauma and OA synovia, tissue factor was seen only in association with vessels (endothelial cells), but in RA synovium, it was markedly increased throughout the tissues. While fibrin D dimer was seen in small amounts in synovial lining cell areas of trauma and OA synovia, it was present in increased amounts in the lining cell and interstitial cell areas of RA synovium. Factor XIII and tissue transglutaminase were present in scant amounts in trauma and OA synovia, but there were increased amounts of both (especially tissue transglutaminase) in RA synovium in the vessel, lining cell, and interstitial cell areas. Urokinase and α2–plasmin inhibitor were also markedly increased in RA synovium. These results suggest that in inflamed synovium, there is ongoing extravascular tissue fibrin formation and dissolution that correlates with the degree of inflammation and macrophage content. Extravascular coagulation/fibrinolysis in RA represents a potential target for therapeutic intervention in this disease.

The IL-6-Soluble IL-6Rα Autocrine Loop of Endothelial Activation as an Intermediate Between Acute and Chronic Inflammation: an Experimental Model Involving Thrombin

“…Detection of fibrin, fibrinogen, and thrombin/antithrombin III complexes in synovial fluids of RA has clearly established the occurrence of extravascular coagulation in RA synovium (47). Thrombin may play a role in RA pathogenesis through induction of MCP-1 and chronic mononuclear cell infiltration as well as induction of IL-8, which favors neutrophil recruitment during acute flare-up of the disease.…”

Changes in the phenotype of monocytes/macrophages and expression of cytokine mRNA in peripheral blood and synovial fluid of patients with rheumatoid arthritis

“…Increased migration of monocytes/ macrophages into the joint results in accumulation of macrophages at the joint surface and thickening of the lining layer. Joint macrophages show increased expression of MHC class II [7,8], CR3 (CDllb/CDI8), pi50,95 (CDllc/CD18) [9], and produce tissue factor [10] and inflammatory cytokines, including IL-l/3 [11] and tumour necrosis factor-alpha (TNF-a) [12]. Interaction between such activated macrophages and type B fibroblastic lining cells results in the formation of an adhesive, enzyme-producing and consequently erosive inflammatory granulation tissue.…”

The Evaluation Of Protein C Activity And Some Inflammatory Markers In Synovia Of Patients Undergoing Total Knee Arthroplasty Surgery

“…Decreased PC activity in the presurgical POA patients may be the result of infl ammation-induced activation of coagulation since extravascular coagulation has been reported to be accelerated in synovia (4,26). Decreased PC activity may refl ect the general state of activation in the infl amed joint as well.…”