Urokinase

Indications

Urokinase injection is indicated in adults:
  • For the lysis of acute massive pulmonary emboli, defined as obstruction of blood flow to a lobe or multiple segments.
  • For the lysis of pulmonary emboli accompanied by unstable hemodynamics, i.e., failure to maintain blood pressure without supportive measures.
The diagnosis should be confirmed by objective means, such as pulmonary angiography or noninvasive procedures such as lung scanning.

Pharmacology

Urokinase is used for the treatment of pulmonary embolisms. The low molecular weight form of human urokinase consists of an A chain of 2,000 daltons linked by a sulfhydryl bond to a B chain of 30,400 daltons. Urokinase is an enzyme (protein) produced by the kidney, and found in the urine. There are two forms of urokinase which differ in molecular weight but have similar clinical effects. Urokinase is the low molecular weight form. Urokinase acts on the endogenous fibrinolytic system. It converts plasminogen to the enzyme plasmin. Plasmin degrades fibrin clots as well as fibrinogen and some other plasma proteins.

Urokinase acts on the endogenous fibrinolytic system. It cleaves the Arg-Val bond in plasminogen to produce active plasmin. Plasmin degrades fibrin clots as well as fibrinogen and other plasma proteins.

Dosage & Administration

Deep vein thrombosis: Initial loading dose of 4,400 IU/kg in 15 mL soln over 10 min, followed by 4,400 IU/kg/hr IV infusion for 12-24 hr. 

Pulmonary embolism: Initial loading dose of 4,400 IU/kg in 15 mL soln over 10 min followed by 4,400 IU/kg/hr IV infusion for 12 hr. 

Peripheral vascular occlusion: Infuse 2,500 IU/mL (500,000 IU in 200 mL) into clot at a rate of 4,000 IU/min for 2 hr.

Advance the catheter into the remaining occluded area & infuse at 4,000 IU/min for another 2 hr. This may be repeated up to 4 times. 

Hyphaema: 5,000 IU in 2 mL saline soln is injected and withdrawn repeatedly over the iris. If residual clot remains, leave 0.3 mL in the anterior chamber for 24-48 hr to facilitate further dissolution. 

Clotted arterio-venous shunts: Instill 5,000-25,000 IU into affected shunt limb & clamp for 2-4 hr, followed by aspiration of lysate. Repeat if necessary.

Interaction

Concomitant use of oral anticoagulant or heparin & drugs that affect platelet function may increase risk of haemorrhage.

Contraindications

Recent surgery or biopsy, severe HTN, severe hepatic or renal insufficiency. Pregnancy & immediate postpartum period.

Side Effects

Overt bleeding, haemorrhagic complications, fever, haematuria, initial severe pain & dull ache in shunt limb.

Pregnancy & Lactation

Pregnancy Category B. Either animal-reproduction studies have not demonstrated a foetal risk but there are no controlled studies in pregnant women or animal-reproduction studies have shown an adverse effect (other than a decrease in fertility) that was not confirmed in controlled studies in women in the 1sttrimester (and there is no evidence of a risk in later trimesters).

Precautions & Warnings

GI lesions & in multiple intracardiac or intravascular punctures as a consequence of cardiopulmonary resuscitation.

Overdose Effects

If severe haemorrhage occurs, treatment with Urokinase-GCC must be stopped. Aprotinin and synthetic inhibitors eg, epsilon aminocaproic acid, tranexamic acid or p-aminomethylbenzoic acid can be used to inhibit the fibrinolytic action of Urokinase-GCC. In serious cases, human fibrinogen, Factor XIII, Cohn-Fraction I, packed red cells or whole blood can be given, as appropriate.

Therapeutic Class

Fibrinolytics (Thrombolytics)

Available Brand Names