INVESTIGATION OF THE FIBRINOLYTIC-ACTIVITY OF DEFIBROTIDE FRACTIONS

1. Defibrotide is a drug which is a mixture of DNA fragments of variou s lengths. To characterize the active component which is responsible f or the fibrinolytic effect, we fractionated defibrotide by column chro matography and investigated direct and endothelium dependent fibrinoly tic activity of the major fractions by euglobulin lysis time (ELT) mea surements. 2. Defibrotide and its fractions added to human plasma samp les did not change ELT. However addition of conditioned media of human umbilical vein endothelial cell cultures which were incubated with de fibrotide or its high molecular weight fractions shortened the ELT sig nificantly (P < 0.001), whereas small molecular weight fractions did n ot effect the ELT. 3. Our results show that high molecular weight defi brotide fractions have fibrinolytic activity and the effect is endothe lium dependent.