Streptokinase

Streptokinase is a bacterial protein from beta haemolytic streptococci that activates plasminogen. It is the cheapest thrombolytic and the one most often available in East Africa for acute ST elevation myocardial infarction when primary intervention is not possible. It is not fibrin specific, so it lowers fibrinogen and causes hypotension and allergy. Antibodies develop after exposure or streptococcal infection, so it should not be repeated within a year.

Classification. Thrombolytic; bacterial plasminogen activator.

Mechanism. Binds plasminogen to form a complex that converts free and clot bound plasminogen to plasmin, which breaks down fibrin and fibrinogen.

Pharmacodynamics. Clot lysis begins within minutes. Fibrinogen, plasminogen and factors V and VIII fall for 24 hours; fibrin degradation products rise.

Pharmacokinetics. Biphasic half life about 20 to 30 minutes. Cleared by antibodies and the reticuloendothelial system.

Acute ST elevation myocardial infarction, adult.

• 1.5 million units IV in 100 mL of 0.9% sodium chloride or 5% glucose over 60 minutes.

• Give within 12 hours of onset, with aspirin 150 to 300 mg loading and then 75 to 100 mg daily.

• Add an anticoagulant (enoxaparin, fondaparinux or unfractionated heparin) after the infusion, as streptokinase does not need concurrent heparin.

Massive pulmonary embolism with shock, adult. Loading dose 250,000 units IV over 30 minutes, then 100,000 units/hour for 24 hours (up to 72 hours for deep vein thrombosis).

Acute arterial occlusion, adult. Specialist use; loading 250,000 units over 30 minutes, then 100,000 units/hour for up to 24 hours.

Children. Specialist use only.

Contraindications.

• Previous streptokinase or anistreplase within 12 months (antibodies).
• Streptococcal infection in the last 5 days to 12 months (including acute rheumatic fever or glomerulonephritis).
• Any history of intracranial haemorrhage.
• Ischaemic stroke in the last 3 months.
• Intracranial or spinal surgery or serious head injury.
• Intracranial tumour, aneurysm or arteriovenous malformation.
• Active internal bleeding, aortic dissection, known bleeding disorder.
• Severe uncontrolled hypertension, hypersensitivity.

Warnings. Hypotension during the infusion (slow or pause it, give fluids, and raise the legs); allergic reactions including anaphylaxis, fever, chills and rash; bleeding; reperfusion arrhythmias; intracranial haemorrhage; do not repeat after 5 days from the first dose.

Adverse effects. Hypotension, bleeding, allergic reaction, fever, nausea, vomiting, arrhythmias, back pain, rarely serum sickness.

Interactions. Anticoagulants, antiplatelet drugs, non steroidal anti-inflammatory drugs: bleeding. ACE inhibitors: increased hypotension.

Reversal of bleeding. Stop the infusion; tranexamic acid 1 g IV over 10 minutes; cryoprecipitate 10 units; fresh frozen plasma if fibrinogen is very low.

Special groups.

• Pregnancy: only when life threatening; limited data.

• Breastfeeding: no data.

• Patients of African ancestry: no dose change.

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

• Kidney impairment: no adjustment.

• Liver impairment: avoid in severe disease.

Formulations. Powder for injection 250,000, 750,000 and 1.5 million units in each vial.

Administration. Reconstitute gently (do not shake) and dilute to 100 mL; give IV over 60 minutes by pump. Keep the arm still and avoid intramuscular injections and unnecessary arterial punctures.

Baseline. ECG, blood pressure, haemoglobin, platelet count, INR, creatinine, history of prior streptokinase and recent sore throat or rheumatic fever.

Monitoring. Blood pressure every 5 to 15 minutes during the infusion; ECG for ST resolution at 90 minutes; rhythm; bleeding signs; neurological state.

Stopping. Stop for anaphylaxis, severe hypotension that does not respond to slowing, or major bleeding.

Common prescribing errors. Repeating it within 12 months; giving it with recent sore throat or rheumatic fever; infusing too fast; omitting aspirin; missing a contraindication; forgetting to start an anticoagulant after the infusion.