Dose:  4400 to 8800 units/kg IV as a loading dose
             4400 to 8800 units/kg/hour as a continuous infusion
             (doses as high as 50,000 units/kg/hour have been used)

Frequency: Continuous infusion

Comments: Urokinase is a human protein obtained from tissue cultures. It acts on the endogenous fibrinolytic system, converting plasminogen to plasmin which degrades fibrin clots as well as fibrinogen and other plasma proteins. The optimal duration of therapy is uncertain as is the optimal dose. Much higher doses may be required in the newborn.  The  recommended dose of urokinase is 4400 units/kg infused as a bolus followed by a continuous infusion of 4400 units/kg/hour; the infusion should be increased until there is improvement in perfusion of the affected area and/or dissolution of the clot is demonstrated.  Others have reported that this is rarely effective and have used an initial dose of 8800 units/kg and double the dose in 4 to 12 hours if treatment is not successful. It is uncertain if therapy is justified beyond 72 hours. Close clinical observation and serial ultrasounds and/or doppler studies are mandatory to document the response to therapy. Laboratory monitoring may be helpful but the degree of increased fibrinolytic activity measured may not correlate with the therapeutic effect in vivo (an increase in plasma D-dimer and a decrease in plasma fibrinogen has been used as an indication of fibrinolysis). Successful fibrinolytic therapy is sometimes accompanied by simultaneous formation of a new thrombus leading to occlusion of the vessel. To prevent this, an infusion of heparin (10 units/kg/hr) given during and after the fibrinolytic therapy has been recommended. More comments on urokinase.  Telephone number for consultation when caring for children with thromboembolic diseases 1-800-NO CLOTS. This is a free consultative service for physicians in North America from Dr. Maureen Andrew and her colleagues in Toronto.

Toxicity: In Giacoia’s review of 35 reported cases (Clin Pediatr 1993; 32:231), aortic thrombosis recurred in one patient and another developed a thrombus in another location. An intraventricular hemorrhage was reported in one preterm infant who died and a germinal matrix hemorrhage was reported in one term infant who survived without sequela. Superficial oozing was reported in three patients, two of whom were premature. Adverse reactions reported in adults include superficial bleeding from needle sticks and internal bleeding (GI, GU, CNS, IM, & retroperitoneal). Fever and bronchospasm can also occur rarely.

Preparation: Urokinase (Abbokinase) is available in a 250,000 unit vial.  reconstitute with 5 ml of sterile water for injection.   Use immediately as a loading dose or mix for a continuous infusion.  When reconstituting or diluting urokinase, use only sterile water for injection without preservatives.  To prepare a 5,000 unit per ml dilution, add 1 ml of the 50,000 units/ml dilution to 9 ml of sterile water. Do not shake, roll and tilt vial. There is some adsorption of urokinase to PVC bags, however a much more significant amount of adsorption occurs in a glass container.  Contains human albumin.

Compatibility: The manufacturer recommends that urokinase be infused only in D5W or normal saline. It is compatible when mixed with heparin and there was no loss in urokinase activity when it was assayed immediately after mixing with TPN. It is compatible with a filter.