Alteplase

Alteplase is a recombinant tissue plasminogen activator, a fibrin specific thrombolytic. It dissolves clot in acute ischaemic stroke, acute myocardial infarction with ST elevation, massive pulmonary embolism, and blocked central venous catheters. It must be given early, as benefit falls with each hour. Intracranial haemorrhage is the main danger. Availability and cost limit its use in East Africa, where streptokinase is more often available.

Classification. Thrombolytic; recombinant tissue plasminogen activator.

Mechanism. Binds fibrin in the clot and converts clot bound plasminogen to plasmin, which breaks down fibrin.

Pharmacodynamics. Clot lysis begins within minutes. Fibrinogen falls modestly because the drug is fibrin selective. Effect lasts a few hours.

Pharmacokinetics. Half life about 4 to 5 minutes (the effect on clot lasts longer). Cleared by the liver.

Acute ischaemic stroke, adult.

• Within 4.5 hours of onset, after imaging has excluded haemorrhage.

• 0.9 mg/kg IV (maximum 90 mg): give 10% as a bolus over 1 minute and the rest over 60 minutes.

• Blood pressure must be under 185/110 mmHg before and under 180/105 mmHg for 24 hours after.

Acute ST elevation myocardial infarction (accelerated regimen), adult.

• 15 mg IV bolus, then 0.75 mg/kg over 30 minutes (maximum 50 mg), then 0.5 mg/kg over 60 minutes (maximum 35 mg).

• Total maximum 100 mg. Give within 12 hours of onset, with aspirin and heparin.

Massive pulmonary embolism with shock, adult. 100 mg IV over 2 hours (or 10 mg bolus over 1 to 2 minutes followed by 90 mg over 2 hours); start heparin at the end of the infusion when the aPTT is under twice control. In cardiac arrest from pulmonary embolism, 50 mg bolus, repeated once after 15 minutes.

Blocked central venous catheter. 2 mg in 2 mL instilled in the lumen for 30 minutes to 2 hours, repeated once if needed.

Children. Systemic use is specialist only; catheter clearance uses 0.5 mg/mL for the lumen volume.

Contraindications.

• Any history of intracranial haemorrhage
• ischaemic stroke in the last 3 months
• intracranial or spinal surgery or serious head injury in the last 3 months
• intracranial tumour, aneurysm or arteriovenous malformation
• active internal bleeding
• aortic dissection
• known bleeding disorder
• platelet count under 100 x 10^9/L
• INR above 1.7 or aPTT raised
• recent direct oral anticoagulant within 48 hours
• blood glucose under 2.7 mmol/L
• uncontrolled blood pressure
• major surgery or trauma within 2 weeks
• gastrointestinal or urinary bleeding in the last 3 weeks
• infective endocarditis (stroke)

Warnings. Intracranial haemorrhage (about 6% in stroke); other bleeding; angioedema (higher with an ACE inhibitor, and in patients of African ancestry); reperfusion arrhythmias; hypotension; blood pressure rise; cholesterol embolism.

Adverse effects. Bleeding, intracranial haemorrhage, angioedema, hypotension, arrhythmia, nausea, fever, allergic reaction.

Interactions. Anticoagulants, antiplatelet drugs, glycoprotein IIb/IIIa inhibitors, non steroidal anti-inflammatory drugs: bleeding. ACE inhibitors: angioedema.

Reversal of bleeding. Stop the infusion; give tranexamic acid 1 g IV over 10 minutes, cryoprecipitate 10 units, and platelets if the count is low.

Special groups.

• Pregnancy: use only when life threatening; limited data; avoid within 10 days after delivery.

• Breastfeeding: no data.

• Patients of African ancestry: higher angioedema risk; no dose change.

• Older adults: higher bleeding risk; no dose change.

• Kidney impairment: no adjustment.

• Liver impairment: avoid in severe disease.

Formulations. Powder for injection, 2, 10, 20 or 50 mg in each vial, with solvent.

Administration. Reconstitute with the solvent supplied to 1 mg/mL (or 2 mg/mL) and give through a dedicated IV line by pump; do not mix with other drugs. Weigh the patient to avoid error.

Baseline. Brain imaging (stroke), ECG (infarction), blood pressure, glucose, platelet count, INR, aPTT, creatinine, pregnancy test where relevant.

Monitoring. Neurological checks and blood pressure every 15 minutes for 2 hours, every 30 minutes for 6 hours, then hourly to 24 hours (stroke); haemoglobin; bleeding signs; ECG and rhythm (infarction). Imaging at 24 hours before starting antithrombotic drugs in stroke.

Stopping. Stop at once for severe headache, vomiting, falling consciousness or major bleeding.

Common prescribing errors. Treating beyond 4.5 hours in stroke; skipping the glucose check; using the maximum of 90 mg wrongly; giving anticoagulants or antiplatelets in the first 24 hours after stroke treatment; missing a contraindication; wrong weight.