Thrombolytic Drugs

Thrombolytic drugs convert plasminogen to plasmin, which degrades fibrin and dissolves clots. They restore flow in STEMI when primary percutaneous coronary intervention cannot be done within 120 minutes, in acute ischaemic stroke within the treatment window, in high-risk pulmonary embolism with shock, and in thrombosed catheters and valves. Haemorrhage, especially intracranial, is the major risk.

Members. Alteplase, tenecteplase, reteplase (fibrin-specific recombinant tissue plasminogen activators); streptokinase (non-fibrin-specific bacterial protein); urokinase.

Mechanism. Fibrin-specific drugs activate plasminogen mainly on the clot surface. Streptokinase forms a complex with plasminogen that activates other plasminogen, causing systemic fibrinogen depletion. Streptokinase is antigenic.

Pharmacokinetics. Alteplase half-life 4 to 6 minutes, tenecteplase 20 to 24 minutes with single bolus, streptokinase 20 minutes. Effect on coagulation lasts hours.

• Alteplase: stroke, STEMI (accelerated infusion), pulmonary embolism, catheter occlusion.
• Tenecteplase: single weight-based bolus; STEMI, stroke in many regions, and pulmonary embolism in specialist use.
• Reteplase: double bolus for STEMI.
• Streptokinase: low cost, widely used in low-resource settings; hypotension and allergy; not repeated within 12 months or after recent streptococcal infection.
• Urokinase: catheter and pleural use.

• STEMI with primary percutaneous coronary intervention not possible within 120 minutes of first medical contact: thrombolysis within 12 hours of symptom onset, ideally within 30 minutes of arrival.
• STEMI, tenecteplase: single bolus by weight: 30 mg under 60 kg, 35 mg for 60 to 69 kg, 40 mg for 70 to 79 kg, 45 mg for 80 to 89 kg, 50 mg for 90 kg or over, with half dose in those aged 75 years or over.
• STEMI, alteplase: 15 mg bolus, 0.75 mg/kg over 30 minutes (maximum 50 mg), then 0.5 mg/kg over 60 minutes (maximum 35 mg).
• STEMI, streptokinase: 1.5 million units over 60 minutes.
• STEMI, adjuncts: aspirin 300 mg, clopidogrel 300 mg (75 mg if over 75 years), and enoxaparin 30 mg intravenous bolus then 1 mg/kg subcutaneously every 12 hours (0.75 mg/kg without bolus if 75 years or over) or unfractionated heparin.
• STEMI, after thrombolysis: transfer to a percutaneous coronary intervention centre afterwards; rescue angioplasty if less than 50% ST resolution at 60 to 90 minutes, and routine angiography within 2 to 24 hours.
• Acute ischaemic stroke: alteplase 0.9 mg/kg (maximum 90 mg), 10% as bolus and remainder over 60 minutes, or tenecteplase 0.25 mg/kg (maximum 25 mg) bolus, within 4.5 hours of onset (or later with imaging selection), after a brain scan excludes haemorrhage. Blood pressure must be under 185/110 mmHg before and under 180/105 mmHg for 24 hours after. Check glucose first.
• Pulmonary embolism with shock: alteplase 100 mg over 2 hours (or 0.6 mg/kg over 15 minutes, maximum 50 mg, in cardiac arrest), followed by unfractionated heparin.
• Catheter occlusion: alteplase 1 to 2 mg instilled into the lumen for 30 to 120 minutes.
• Selection: use fibrin-specific agents where available. Streptokinase remains effective for STEMI when access or cost are barriers.

Absolute contraindications. Previous intracranial haemorrhage, ischaemic stroke in the past 3 months (except within the stroke treatment window), intracranial tumour or vascular malformation, significant head or facial trauma in the past 3 months, active internal bleeding, suspected aortic dissection, and (for stroke) blood pressure not controlled to under 185/110 mmHg, glucose under 2.7 mmol/L, and platelets under 100 x 10^9/L or INR over 1.7.

Relative contraindications. Anticoagulant use, pregnancy or within 1 week postpartum, recent major surgery or trauma (within 3 weeks), recent gastrointestinal bleeding, severe hypertension at presentation, traumatic or prolonged resuscitation, and for streptokinase previous exposure.

Adverse effects. Bleeding (intracranial haemorrhage in about 0.5% to 1% in STEMI and about 6% in stroke), reperfusion arrhythmia, hypotension (streptokinase), allergic reaction and angioedema (rate raised with ACE inhibitors, mainly in stroke), and re-occlusion.

Management of bleeding. Stop the infusion, give tranexamic acid 1 g intravenously, cryoprecipitate 10 units (to fibrinogen over 1.5 g/L), fresh frozen plasma and platelets where needed, with neurosurgical review if intracranial. Angioedema: stop infusion, give antihistamine, corticosteroid and adrenaline as needed.

Interactions. Anticoagulants, antiplatelet drugs and glycoprotein IIb/IIIa inhibitors raise bleeding. ACE inhibitors raise angioedema risk.

Monitoring. Neurological observations every 15 minutes during and after stroke thrombolysis, blood pressure, rhythm, ST resolution at 60 to 90 minutes, bleeding at puncture sites, and no arterial punctures, invasive procedures or anticoagulants in the first 24 hours after stroke thrombolysis.

Referral and escalation. Patients need monitored care (coronary care, stroke unit or high dependency) and transfer for angiography. Severe headache, vomiting or neurological decline after thrombolysis needs urgent imaging.

Special groups. Older adults: lower dose of tenecteplase in STEMI, higher haemorrhage risk. Pregnancy: used only when life is threatened. Children: specialist indications only. Region: record streptokinase use in the patient's notes and card to avoid repeat exposure.