Urokinase

Urokinase is used for: Acute MI, Pulmonary embolism, Thromboembolism, Deep vein thrombosis

Intravenous Deep vein thrombosis Adult: Initially, 4400 units/kg dissolved in 15 ml of sodium chloride 0.9%, infused IV over 10 minutes followed by 4400 units/kg/hr for 12-24 hr. Parenteral Acute myocardial infarction Adult: 6000 units/min infused into the coronary artery for 2 hr preceded by IV heparin. Alternatively, 2-3 million units IV is given over 45-90 min. Intravenous Peripheral arterial thromboembolism Adult: As solution containing 2000 units/ml: Infuse into the clot via a catheter at a rate of 4000 units/minute for 2 hr. Monitor response using angiography. If clot is not removed, advance the catheter into the occluded vessel and continue infusion at the same rate for another 2 hr. May repeat procedure, if needed, up to 4 times. Once blood flow is re-established, partially withdraw the catheter and continue infusing at 1000 units/minute until the remaining clot has lysed. Pulmonary embolism Adult: Initially, 4400 units/kg dissolved in 15 ml sodium chloride 0.9%, infused over 10 min followed by 4400 units/kg/hr for 12 hr. Alternatively, 15000 units/kg as bolus Inj into the pulmonary artery; may repeat inj, adjust dose according to plasma fibrinogen concentrations up to 3 times in 24 hr. Injection Clearance of occluded catheters and shunts Adult: 5000 - 25000 units in 2 ml sodium chloride 0.9% instilled into affected IV catheter or shunt and clamped for up to 4 hr. Aspirate the lysate and repeat the procedure if needed. Alternatively, infuse a solution containing 5000 units of urokinase in 200 mL of sodium chloride 0.9% into the device over 30 minutes. Irrigation Break down of clots in hyphaema Adult: To prepare the solution: Dissolve 5000 units in 2 ml of sterile distilled water. Irrigate the anterior chamber slowly with 0.3 ml of the solution; leave solution in situ for 3 minutes and then wash out with saline. Repeat procedure 5 times. If residual clot is still present at the end of the treatment, leave 0.3 ml of the solution in the anterior chamber for 24-48 hr.

Active internal bleeding; history of cerebrovascular accident; recent (within 2 mth) trauma of any kind including surgery; aneurysm; known bleeding diathesis; severe uncontrolled hypertension. Recent history of peptic ulcer disease, oesophageal varices, ulcerative colitis or other bleeding GI lesions; pancreatitis; subacute bacterial endocarditis; coagulation defects including those due to liver or kidney disease, or after recent surgery, childbirth or trauma. Increased risk of cerebral bleeding e.g. recent stroke or cerebral neoplasm. Pregnancy.

Any vascular punctures or invasive procedures should be avoided as far as possible during, and immediately before and after urokinase therapy and if unavoidable done with great care. External chest compression. Caution in conditions eg, possibility of left heart thrombus, subacute bacterial endocarditis, coagulation defects, cerebrovascular disease, diabetic retinopathy and any conditions in which bleeding could be dangerous. Monitor for reperfusion arrhythmias when used in MI.

Reduced thrombolytic effect when given again some time later due to development of high levels of antibodies. Potentially Fatal: Platelet inhibitors eg, aspirin and indometacin can potentiate the action of urokinase and cause haemorrhage. Heparin and oral anticoagulants may increase risk of bleeding.

Side effects of Urokinase : Bleeding, pyrexia, haematuria, thromboembolic episodes, hypersensitivity reactions. Potentially Fatal: Severe bleeding, anaphylaxis.

Urokinase, an enzyme isolated from human urine, directly converts plasminogen into plasmin, which is a proteolytic enzyme with fibrinolytic effects. It is a fibrin non-specific thrombolytic as it affects both unbound and fibrin bound plasminogen.