ELASTASE-MEDIATED AND PLASMIN-MEDIATED FIBRINOLYSIS IN RHEUMATOID-ARTHRITIS

Selected coagulation and fibrinolytic factors were evaluated in plasma and synovial fluid (SF) of 10 rheumatoid arthritis (RA) patients, inc reased levels of fibrinogen were observed in plasma (p < 0.01), but on ly a trace amount of structurally intact fibrinogen was detected in th e SF of RA patients, while immunostaining showed deposits of insoluble fibrin in their synovial membranes. Reduced levels of protein C, anti thrombin III and coagulation factors II, V, VII, VIII, IX, XII and XII I (p < 0.01), and high levels of thrombin-antithrombin III (TAT) compl exes (p < 0.01), were found in SF as compared to their corresponding p lasma levels. The increased levels of fibrinogen, TAT complexes, B bet a 15-42 peptide and plasminogen activator inhibitor-1 (PAI-1) in plasm a (p < 0.01) are consistent with an enhanced fibrin turnover and endot helial perturbation due to a systemic inflammatory state. Plasminogen and alpha(2)-plasmin inhibitor activity in SF were significantly reduc ed as compared to the plasma levels (p < 0.01), whereas an increase in PAI-1 activity was found in SF as compared to plasma (p < 0.01). The detection of D-dimer and BP 15-42 peptide (p < 0.01) in SF suggests an involvement of plasmin in the degradation of fibrin generated in syno vial tissue. The high levels of elastase-alpha(1)-proteinase inhibitor complexes and of thrombin-increasable fibrinopeptide A, as well as th e pattern of fibrinogen degradation as identified in SF by double-dime nsion immunoelectrophoresis, suggest that elastase released from exuda ted granulocytes may play an important role in fibrino(geno)lysis and tissue damage in RA joints.