What is the recommended dose of streptokinase for thrombolytic therapy?

Streptokinase Dosing for Thrombolytic Therapy

Standard Dosing Regimens by Indication

Acute Myocardial Infarction (STEMI)

The recommended dose is 1.5 million units administered intravenously over 30-60 minutes. 1 This represents the standard regimen validated in major trials and endorsed by both European and American cardiology societies.

• Administer as 1.5 million units in 100 mL of 5% dextrose or 0.9% saline over 30-60 minutes 1
• No weight-based adjustment is required for this indication 1
• Initiate treatment as soon as possible within 12 hours of symptom onset if primary PCI cannot be performed within 90 minutes of first medical contact 1

Prosthetic Valve Thrombosis

For left-sided prosthetic valve thrombosis, administer a 250,000 unit bolus over 30 minutes, followed by continuous infusion of 100,000 units/hour. 1, 2

• The loading dose of 250,000 units should be given over 30 minutes 1
• Maintenance infusion continues at 100,000 units/hour 1
• Duration varies from 2-120 hours depending on hemodynamic response, typically stopping when pressure gradients normalize or after 72 hours maximum 1
• Monitor with Doppler echocardiography every 2-3 hours in obstructive cases 1, 2
• Alternative regimen: Some centers use 500,000 units over 20 minutes followed by 1.5 million units over 10 hours 1

Pulmonary Embolism

The standard dose is 250,000 units as a loading dose over 30 minutes, followed by 100,000 units/hour infusion. 1

• This regimen mirrors the prosthetic valve thrombosis protocol 1
• Treatment duration typically extends until clinical improvement is achieved 1
• In massive pulmonary embolism with hemodynamic instability, thrombolytic therapy is strongly indicated despite hypotension 3

Deep Venous Thrombosis

A lower-dose regimen of 250,000 units bolus followed by 100,000 units/hour (maximum 4 million units total) has demonstrated efficacy with acceptable safety. 4

• This low-dose systemic approach achieved 56% recanalization rates versus 5% with heparin alone 4
• Best results occur when treatment begins within 4 days of symptom onset 4
• Hemorrhagic complications occurred in only 4% of patients with this regimen 4

Critical Contraindications and Precautions

Absolute Contraindications

• Previous intracranial hemorrhage or stroke of unknown origin at any time 1
• Ischemic stroke within preceding 6 months 1
• Central nervous system damage, neoplasms, or arteriovenous malformations 1
• Recent major trauma, surgery, or head injury within 3 weeks 1
• Gastrointestinal bleeding within the past month 1
• Known bleeding disorder 1
• Aortic dissection 1

Relative Contraindications

• Refractory hypertension (systolic >180 mmHg and/or diastolic >110 mmHg) 1
• Severe uncontrolled hypotension (systolic <90 mmHg) requires careful risk-benefit assessment 3
• Pregnancy (generally relative, but may proceed if maternal life is threatened) 1

Streptokinase-Specific Contraindications

Never readminister streptokinase to patients with prior exposure, as antibodies persist for at least 10 years and can impair activity or cause severe allergic reactions. 1, 2

• Prior streptokinase or anistreplase exposure is an absolute contraindication to repeat use 1, 2
• Switch to urokinase (4,400 units/kg/hour) in patients with known streptokinase allergy or previous exposure 1, 2
• Patients with anti-streptococcal antibodies may have reduced efficacy 1

Administration and Monitoring

Hypotension Management During Infusion

Streptokinase commonly causes transient hypotension that is rate-related and typically manageable without discontinuation. 3

• Monitor blood pressure every 5 minutes during the first 20 minutes of infusion 3
• If hypotension develops, temporarily halt or slow the infusion rate 3
• Position patient flat with legs elevated and administer IV fluids as needed 3
• Slower infusion rates (extending toward 60 minutes rather than 30 minutes) may reduce severity of hypotension 3
• Do not use routine prophylactic hydrocortisone 3

Hemodynamic Monitoring

• Perform baseline coagulation studies, but do not delay treatment in acute settings 1
• Monitor for lytic state at 24 hours: expect increased D-dimer and aPTT, decreased fibrinogen 1
• If no lytic state is documented at 24 hours, consider switching to urokinase (antibodies may be blocking streptokinase activity) 1

Duration of Treatment

• Stop infusion when hemodynamic parameters normalize or near-normalize 1
• Discontinue if no improvement after 24 hours or after 72 hours maximum even without complete recovery 1, 2
• In prosthetic valve thrombosis, TEE should be performed at 24,48, and 72 hours if thrombus persists 1

Adjunctive Anticoagulation

During Streptokinase Infusion

Do not administer concomitant heparin during active streptokinase infusion for most indications. 2

• Streptokinase exerts significant intrinsic anticoagulant effects 5
• Unlike tissue plasminogen activator, streptokinase does not require simultaneous heparin for STEMI 1
• Optional: IV heparin for 24-48 hours may be considered after streptokinase completion 1

Post-Thrombolysis Anticoagulation

• Initiate or resume heparin when aPTT or thrombin time returns to twice normal or less 1
• Target aPTT 50-70 seconds when heparin is used 1
• Transition to warfarin with INR goals of 2.5-3.5 for aortic prosthetic valves and 3.5-4.5 for mitral prosthetic valves 1

Antiplatelet Therapy

• Aspirin 150-325 mg should be chewed immediately (or 250 mg IV if oral not possible), then 75-160 mg daily 1
• Clopidogrel 300 mg loading dose followed by 75 mg daily reduces cardiovascular events when added to aspirin in STEMI patients ≤75 years 1

Common Pitfalls and How to Avoid Them

Dosing Errors

• Do not use weight-based dosing for STEMI: The 1.5 million unit dose is fixed regardless of patient weight 1
• Do not confuse with alteplase dosing: Streptokinase uses fixed units, not mg/kg calculations 1, 6
• Do not reduce initial dose below 250,000 units for the bolus: Lower initial doses (when used historically) were associated with higher mortality in peripheral arterial occlusions 7

Timing Mistakes

• Do not use streptokinase for acute ischemic stroke: Three trials were halted prematurely due to excess deaths and poor outcomes 3, 8
• Do not delay treatment for complete coagulation results in life-threatening situations: Begin immediately in STEMI or massive PE 1
• Do not extend treatment beyond 72 hours: No additional benefit and increased bleeding risk 1

Safety Oversights

• Do not ignore prior streptokinase exposure history: Antibodies render repeat dosing ineffective and dangerous 1, 2
• Do not use in patients with systolic BP >180 mmHg or diastolic >110 mmHg without first controlling blood pressure: This is a relative contraindication requiring correction 1
• Do not perform surgery within 24 hours of stopping streptokinase: Wait for fibrinolytic activity to resolve or use protease inhibitors for urgent surgery within 2 hours 1

Monitoring Failures

• Do not assume thrombolysis failed without documenting a lytic state: Check D-dimer, aPTT, and fibrinogen at 24 hours 1
• Do not continue infusion if intracranial hemorrhage is suspected: Stop immediately and obtain urgent CT scan 2