Degradation Of Plasmin-Resistant Fibrinogen-Fibrin Breakdown Products In Rheumatoid Synovial Fluid By Brinastrase

Plasmin-resistant protamine sulphate pre-cipitable fibrinogen-fibrin breakdown products are found in high concentrations in rheumatoid synovial fluids. The resistance of proteolytic activity might be due partly to cross-link formation between fibrin monomers catalysed by the activity of fibrin-stabilizing factor (FSF) and partly to complex formations. The persistence of these fibrin formations might influence the course of the disease. Brinasrrase® is a proteolytic enzyme obtained from Aspergillus oryzae. In vitro incubation of this enzyme with rheumatoid synovial fluids produces a significant and profound degradation of the plasmin-resistant protamine sulphate precipitable antigenic fibrinogen-fibrin breakdown products into low molecular weight fractions the more resistant of which exhibit E-antigenicity, whereas plasmin digestion is followed by incomplete degradation, leaving high molecular weight E-antigenic fractions, reminding of those seen during digestion of stabilized fibrin. Intra-articular injections in 4 patients with rheumatoid arthritis produce a similar profound degradation and repeated injections will temporarily clear the joints of F.R.A. The concentrations of inhibitors alpha-1 antitrypsin and alpha-2 macroglobulin decrease immediately after the injection but higher concentrations are found 2 or 3 days later. These higher concentrations do not, however, neutralize repeated injections of the enzymes.