The Effect of Heparin on Components of the Human Fibrinolytic System

F IBRINOLYSIS induced in human beings for the treatment of thromboembolic disorders may remove the result of intravascular clotting, but not its underlying cause. For the prevention of the reformation of intravascular clots, a combined treatment of fibrinobysis-inducing agents with an anticoagulant is indicated. An additional reason for combining fibrinolytic treatment with anticoagulant administration is the finding that fibrinolysis enhances clotting. This was observed in vitro by inducing fibrinolysis in human plasma with streptokinase and swine plasmin,7 in vivo, after injection of plasmin in dogs3 and during pyrogen-induced fibrinolysis in man.7’8 Our observations of pyrogen-induced fibrinolysis in man suggest that the more recent the origin of palpable thrombi, the more rapidly and completely regression occurs. We therefore used heparin as the anticoagulant of choice during induced fibrinolysis, thus being able to start a combined treatment immediately. On two occasions, however, it was observed that patients to whom a large dose of heparin was given shortly before the pyrogen injection did not respond in the usual manner with a marked fibrinolysis 105 to 120 minutes after pyrogen injection. These findings prompted investigation of the effect of heparin on individual components of the human fibrinolytic enzyme system. The divergent opinions on this subject expressed in the rather scanty literature seemed to us to justify these studies.