ASSESSMENT OF COAGULATION AND FIBRINOLYSIS IN SYNOVIAL-FLUID OF RHEUMATOID-ARTHRITIS PATIENTS

In order to understand the mechanism of fibrin deposition in the synovia during the progression of rheumatoid arthritis (RA), activities of coagulation factors, fibrinolytic enzymes, and corresponding inhibitors were measured in synovial fluid of 12 RA patients. Almost all of the synovial fluid (SF) fibrinogen molecules were found to be fragmented and some portions of the molecule that were slightly affected were found to be in a complex with albumin molecules. Immunohistochemical analysis showed deposits of insoluble fibrin in synovial membranes and pannus, in levels related to the progression of disease. Coagulation factor VII, VIII, X, XII, and XIII activities in SF were found to be 30 to 50% of plasma levels but factors II and V activities were less than 25% of plasma levels. Protein C and antithrombin III activities in SF were 30% of plasma levels. However, the two orders of magnitude, higher level of thrombin-antithrombin HI (TAT) complex in SF than in plasma, suggests a steady activation of coagulation cascade in synovia. The observed increased levels of fibrinogen, TAT complexes, B beta 15-42 peptide and plasminogen activator inhibitor-1 (PAI-1) in plasma are consistent with the systemic inflammatory state of RA patients. Although a 30% decrease in plasma levels of alpha(2)-plasmin inhibitor activity, acid a 2-fold higher level of PAI-1 activity in SF were found, the presence of D-dimer and B beta 15-92 peptide in SF suggests an active participation of plasmin in the fibrino(geno)lysis. In addition, elevated levels of elastase-alpha(1)-proteinase inhibitor complexes and of thrombin-increasable fibrinopeptide A in SF suggest the participation of leukocyte elastase in fibrin(ogen)olysis as well.