THE INTRAVENOUS INFUSION OF THE STREPTOCOCCAL FIBRINOLYTIC PRINCIPLE (STREPTOKINASE) INTO PATIENTS 1

Abstract

Streptokinase (contained in Varidase), in amounts ranging from 75,000 to 150,000 units, was given intravenously to patients, 11 of whom were studied in detail as described in this article. Both continuous and intermittent infusions of 4-5 hour duration were used. The hematological effects have consisted chiefly of polymorphonuclear leucocytosis, and some irregular variations in platelet counts with no appreciable alteration of the clotting time or bleeding time. Moderate prolongations of prothrombin time occurred following the creation of active fibrinolytic systems in patients with low titers of naturally occuring inhibitor. No alterations in prothrombin time were observed in patients with high inhibitor in whom active fibrinolysis did not develop. The principal toxic manifestations were pyrogenic reactions which were well controlled by the administration of amidopyrine, and hypotensive effects for which Chlor-Trimeton was given. The decreases in blood pressure were usually maximal 8-24 hours after termination of the infusion and usually returned to normal during the following 24 hours. Systolic blood pressure was affected more than diastolic. No symptoms attended lowering of the blood pressure. An active fibrinolytic system was developed in 6 of the 7 patients who received continuous infusions for 4-5 hours, and in 5 of the 7 100% fibrinolytic activity was attained. After termination of the infusion, lytic activity remained 100% for 1-3 hours and then decreased with varying degrees of partial activity persisting for 4-30 hours depending to a considerable degree on the amount of "natural inhibitor" present in the individual patient''s blood. Repeated infusions (two times in three, and three times in one patient) were given in which the 2nd or 3rd infusion represented a "booster" dose. The degree and duration of fibrinolytic activity was greater and persisted longer in 3 of the 4 patients of this group than in those receiving a single infusion even though the total amount of streptokinase (SK) was essentially the same. When an active lytic system was developed in patients with low inhibitor concomitant decreases occurred in fibrinogen, plasminogen, and complement. When no lytic activity occurred in patients with high inhibitor, no fibrinogenolysis or fibrinolysis occurred, but there were significant but lesser decreases in both plasminogen and com-plement.