The fibrinolytic system and thrombotic tendency.

The deposition of the insoluble protein matrix, fibrin is temporary. The mainly known mechanism of proteolytic removal is orchestrated by a cascade type of proteolytic process involving ultimately the formation from plasminogen of the active degradation enzyme plasmin. The occurrence of plasminogen deficiency without a massive deposition of fibrin and thrombotic events indicates the occurrence of alternate routes of fibrin degradation. In the literature, data have been reported about the direct fibrinolytic activity of various other enzymes including leucocytal elastase and cathepsin G and three metalloproteinases (MMP-3,MMP-7, MT1-MMP). The importance of each of these pathways and the possible differences in importance in various diseases, in acute situations and at different locations in the circulation, in tissues and organs is not known in detail. It is suggested that multiple combined knock-outs be created to evaluate the situation for various well-defined phenotypes. It is concluded that fibrin removal is an important biological process with various buffering mechanisms and only combinations of abnormalities in the various mechanisms and special situations will lead to fibrin accumulation and thrombotic events.