Plasmin fibrin dissolution

The kinetics of the lytic effect displayed by the complexes of immobilized heparin with thrombin and fibrinogen, in distinction from those with plasmin, are described by their saturation curves. The observed slowing down of the dissolution of unstabilized fibrin is probably due to the inhibiton of the lytic activity of the complexes by the soluble products of the reaction. In fact, as it was shown in Ref. 106, further addition of immobilized heparin-protein complex to partially hydrolyzed fibrin results in a complete recovery of the dissolution rate. 

Thrombolytics facilitate the breakdown and dissolution of clots that have already formed. These drugs work by converting plasminogen (profibrinolysin) to plasmin (fibrinolysin).34 As shown in Figure 25-1, plas-min is the active form of an endogenous enzyme that breaks down fibrin clots. Thrombolytic drugs activate this enzyme by various mechanisms and can be used to dissolve clots that have already formed, thus reopening occluded blood vessels. 

Tranexamic acid competitively inhibits the binding of plasminogen and t-PA to fibrin and effectively blocks conversion of plasminogen to plasmin (which causes dissolution of fibrin) fibrinolysis is thus retarded. After an i.v. bolus injection it is excreted largely unchanged in the urine the t] is 1.5 h. It may also be administered orally or topically. 

Plasminogen is the precursor of the serine protease plasmin which is involved in dissolution of fibrin clots and, hence, in removal of thrombi. The plasma concentration is about 12mg/100ml and the molecular mass 81 kDa. It contains 17.1% carbohydrate on two sites, one N-linked and one O-linked oligosaccharide. A variant is also known that is only 0-glycosylated. The structures of the oligosaccharides have been determined [71-73], and are shown in Fig. 11. 

B. Mechanism of Action Plasmin is the normal endogenous fibrinolytic enzyme. By splitting fibrin into fragments, plasmin promotes the breakdown and dissolution of clots (Figure 34-3). The thrombolytic enzymes catalyze the activation of the inactive precursor, plasminogen, to plasmin. 

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