Generic Name

Urokinase

Mechanism

• Direct activation of plasminogen.
• Urokinase binds to the plasminogen form on fibrin surfaces, converting it to plasmin, a broad‑spectrum fibrinolytic enzyme that degrades fibrin clots.
• Fibrin‑specific activity.
• Unlike tissue plasminogen activator (tPA), uPA has less affinity for the fibrin surface but releases plasmin rapidly, leading to potent clot dissolution.
• Inhibition by α2‑antiplasmin is minimal at therapeutic concentrations, allowing sustained fibrinolysis.

Pharmacokinetics

> Key point: The short half‑life necessitates continuous intravenous infusion or repeated boluses for clot dissolution.

Indications

• Acute pulmonary embolism (PE) – within 48 h of symptom onset.
• Acute myocardial infarction (AMI) – as adjunct to coronary reperfusion when fibrinolysis is preferred.
• Deep vein thrombosis (DVT) – particularly in patients who cannot receive anticoagulation.
• Renal thromboembolism – e.g., nephrectomy or renal vein thrombosis.
• Cardiac surgery – to prevent clot formation on prosthetic surfaces (off‑label use).

(Use in acute ischemic stroke is contraindicated; only tPA is approved.)

Contraindications

• Absolute contraindications:
• Recent intracranial hemorrhage or any spontaneous bleeding.
• Uncontrolled hypertension (SBP > 185 mmHg or DBP > 110 mmHg).
• Active bleeding or major surgery within the last 12 h.
• Known severe hepatic disease.
• Relative contraindications:
• Severe aortic stenosis (risk of embolization).
• Severe coronary artery disease (risk of arrhythmias).
• Pregnancy (thrombolytic therapy increases fetal risk).
• Warnings:
• Severe allergic reactions (anaphylaxis).
• Renal impairment may prolong plasma half‑life.
• Use caution in patients with thrombocytopenia or platelet dysfunction.

Dosing

• IV catheter insertion into a large vein (jugular or central).
• Monitor infusion line for clot formation.

*Dosing adjustments* → Reduce infusion by 20 % in renal impairment; pediatric dosing ~1–2 mg/kg/day divided into 3‑4 doses.

Adverse Effects

• Common
• *Bleeding* – epistaxis, gum bleed, hematoma at IV site.
• *Anaphylaxis* or urticaria (rare).
• *Hypotension* (flushing, rapid drop in BP).
• *Flu‑like symptoms* (fever, chills).
• Serious
• Intracranial hemorrhage.
• Hemorrhagic gastritis / GI bleeding.
• Disseminated intravascular coagulation (post‑infusion).
• Severe allergic reaction → anaphylactic shock.

Monitoring

• Baseline (pre‑infusion):
• CBC with differential (platelets).
• PT/INR, aPTT, fibrinogen, D‑dimer.
• BMP & liver panel.
• During infusion (every 30 min):
• Blood pressure & pulse.
• Urine output (renal function).
• Post‑infusion (6–12 h):
• Repeat CBC, fibrinogen, D‑dimer.
• Neuro‑check for signs of bleeding.
• Long‑term:
• Follow‑up coagulation profile after 24–48 h to ensure no persistent hyper‑fibrinolysis.

Clinical Pearls

• Early Start Wins: Initiating urokinase within the first 24–48 h of PE/AMI dramatically improves survival; later administration yields diminishing returns.
• Bolus vs. Infusion: The bolus‑only regimen (6 µg/kg) is preferred when bleeding risk is high; the infusion provides continuous fibrinolytic activity but carries higher hemorrhage incidence.
• Avoid Concomitant Anticoagulants Early On: Start therapeutic anticoagulation only after stable infarction resolution (typically 24 h post‑infusion) to minimize bleed risk.
• Renal Function Matters: In patients with eGFR  100 × 10⁹/L before initiating therapy; if lower, delay until correction to reduce hemostatic failure.
• IV Access Integrity: Because urokinase is proteinaceous, ensure infusion line is flushed with normal saline to prevent precipitation and catheter occlusion.
• Contraindication Check: Always rule out active internal bleeding via imaging (CT/MRI) before administration; the risk of precipitating catastrophic hemorrhage is unacceptable.

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• *These guidelines align with current evidence and are ideal for quick reference by medical students, pharmacists, and clinical practitioners.*