Summary
The fibrinolytic potency of several polyanions was comparatively investigated. Fibrinolytic
activity was measured in a whole plasma assay using H-D-Val-Leu-Lys-pNA (S-2251) as
chromogenic substrate and by a fibrin plate assay using plasminogen rich fibrin plates.
In the chromogenic substrate assay potent fibrinolytic polyanions comprised dextran
sulfate, GAGPS, pentosan polysulfate, polyanethol sulfate, 1-carrageenan and i-carrageenan.
Chon- droitin sulfates A, B, ‘C, keratan sulfate, ribonucleic acid, k-carrageenan
and heparin were weakly fibrinolytic. Hyaluronic acid and lipopolysaccharide from
E. coli were inactive.
Similar results were obtained when fibrinolytic activity was measured by a fibrin
plate assay. All polyanions except lipopolysaccharide produced lysis zones.
Induction of fibrinolytic activity in human plasma was shown to be at least partially
dependent on Hageman factor. In factor XII deficient plasma no fibrinolysis was induced
by any of the polyanions when measured in the fibrin plate assay.
In the. chromogenic substrate assay corn Hageman factor inhibitor (CHFI) inhibited
the activation of S-2251 cleaving enzyme by GAGPS, pentosan poly sulfate, polyanethol
sulfate, heparin, and ribonucleic acid near completely. The activation by dextran
sulfate was inhibited by 45%.
Heparin, pentosan polysulfate and GAGPS, three poly anions of therapeutic interest
were separately compared. In both assays GAGPS proved the most potent activator, while
pentosan poly sulfate exhibited 83% and 44% and heparin 32% and 14% of GAGPS fibrinolytic
activity in the chromogenic substrate test and the fibrin plate assay, respectively.
Keywords
Fibrinolysis - Hageman factor - Polyanions - Sulfated polysaccharides
