What is the role of streptokinase in pulmonary embolism thrombolysis?

Streptokinase for Pulmonary Embolism Thrombolysis

Streptokinase is indicated for high-risk (massive) pulmonary embolism with shock or hypotension, where it significantly reduces mortality compared to heparin alone, but it has been largely superseded by rtPA due to slower hemodynamic improvement and higher rates of allergic reactions. 1

Indications for Streptokinase

High-Risk (Massive) PE - Clear Indication

• Streptokinase should be administered to patients with PE presenting with shock or hypotension (systolic BP <90 mmHg or pressure drop of 40 mmHg for >15 minutes) unless absolute contraindications exist 1
• Meta-analysis data shows thrombolysis (including streptokinase) in massive PE reduces the combined outcome of recurrent PE or death from 19.0% to 9.4% (OR 0.45,95% CI 0.22-0.92) 1
• One small randomized trial specifically comparing streptokinase to heparin in high-risk PE found all 4 patients treated with heparin died, while all 4 treated with thrombolysis survived—this difference was so significant the trial was stopped early for ethical reasons 1

Intermediate-Risk (Submassive) PE - Unclear Benefit

• In normotensive patients with RV dysfunction and elevated troponins, the benefit of thrombolysis is not established 1
• Mortality in submassive PE is less than 5% with anticoagulation alone, making any benefit from thrombolysis unlikely to outweigh bleeding risks 1

Low-Risk PE - Not Indicated

• When vascular obstruction is <50% without hemodynamic compromise, thrombolysis provides no benefit and should not be used 1

Dosing Regimens

Standard Regimen

• Loading dose: 250,000 IU over 30 minutes 1
• Maintenance: 100,000 IU/hour for 12-24 hours 1
• Hydrocortisone should be co-administered to reduce allergic reactions 1

Accelerated Regimen

• 1.5 million IU over 2 hours 1
• This regimen produces faster hemodynamic improvement compared to the standard 24-hour infusion, though the difference is limited to the first hour 1

High-Dose Short-Term Regimen

• 1,500,000 IU over 1 hour has been studied in 40 patients with large or massive PE, showing reversal of pulmonary hypertension and RV dysfunction in 35 patients without increased hemorrhagic complications 2

Comparison to Other Thrombolytics

rtPA (alteplase) is now preferred over streptokinase for most patients due to faster hemodynamic improvement and fewer systemic reactions. 1

• rtPA (100 mg over 2 hours) produces more rapid hemodynamic improvement than streptokinase (1.5 million IU over 2 hours), though this difference is mainly evident in the first hour 1
• rtPA has lower rates of hypotension, fever, and chills compared to streptokinase 1
• No mortality difference has been demonstrated between streptokinase, urokinase, and rtPA in controlled studies 1
• The faster hemodynamic effect of rtPA may be clinically relevant in the sickest patients with massive PE 1

Safety Profile and Bleeding Risk

Major Bleeding Rates

• Major bleeding occurs in approximately 21.9% of patients receiving thrombolysis for massive PE compared to 11.9% with heparin alone (OR 1.98,95% CI 1.00-3.92) 1
• Intracranial hemorrhage occurs in 1.7-1.9% of patients receiving thrombolysis 1
• Bleeding at venous puncture sites accounts for 36-45% of major hemorrhages 1

Streptokinase-Specific Concerns

• Streptokinase is highly antigenic and develops neutralizing antibodies, precluding its use in subsequent episodes 1
• Patients with known allergy to streptokinase or previous exposure should receive urokinase or rtPA instead 1
• Allergic reactions necessitate hydrocortisone co-administration 1

Absolute Contraindications

• History of hemorrhagic stroke or stroke of unknown origin 1
• Ischemic stroke in previous 6 months 1
• Central nervous system neoplasm 1
• Major trauma, surgery, or head injury in previous 3 weeks 1
• Active bleeding 1
• Bleeding diathesis 1

Relative Contraindications

• Transient ischemic attack in previous 6 months 1
• Oral anticoagulation 1
• Pregnancy or first postpartum week 1
• Non-compressible puncture sites 1
• Traumatic resuscitation 1
• Refractory hypertension (systolic BP >180 mmHg) 1

In patients with massive PE, most contraindications become relative rather than absolute due to the high mortality risk without thrombolysis. 1

Administration and Monitoring

Route of Administration

• Thrombolytic therapy is equally effective via peripheral vein or pulmonary artery catheter 1
• Local intrapulmonary arterial administration has been studied with low-dose streptokinase (10,000-20,000 units/hour), showing efficacy but still carrying bleeding risk 3, 4

Monitoring During Treatment

• In obstructive PVT, Doppler echocardiography should be performed every 2-3 hours for hemodynamic monitoring 1
• Stop infusion when pressure gradients and valve areas return to normal or near-normal 1
• If no hemodynamic improvement occurs at 24 hours, or after 72 hours even without complete recovery, discontinue streptokinase 1

Transition to Anticoagulation

• Heparin should be started when APTT or thrombin time returns to twice normal or less, typically near the end of or immediately following streptokinase infusion 1, 5
• Continue heparin for at least 5 days and overlap with warfarin until INR is 2.0-3.0 for 2 consecutive days 1

Clinical Efficacy and Timing

Time Window for Treatment

• Greatest benefit occurs when treatment is initiated within 48 hours of symptom onset 1
• Thrombolysis can still be useful in patients with symptoms for 6-14 days 1
• Treatment should be initiated as soon as possible after diagnosis in high-risk PE 1

Hemodynamic Improvement

• Streptokinase leads to faster improvements in pulmonary obstruction, pulmonary artery pressure, and pulmonary vascular resistance compared to heparin alone 1
• These improvements are accompanied by reduction in RV dilation on echocardiography 1
• Clinical improvement typically occurs within 4-12 hours, with angiographic improvement evident at 12-24 hours 6, 3, 4

Common Pitfalls and Caveats

• Do not use streptokinase in patients with previous streptokinase exposure due to antibody formation 1
• Avoid invasive procedures and arterial punctures during and immediately after thrombolysis to minimize bleeding risk 1
• In high-risk PE patients, unfractionated heparin is preferred over LMWH or fondaparinux as initial anticoagulation, as the latter have not been tested in shock states 1
• Unsuccessful thrombolysis (persistent clinical instability and unchanged RV dysfunction after 36 hours) occurs in approximately 8% of high-risk PE patients and should prompt consideration of surgical embolectomy 1
• If thrombolysis fails or is contraindicated, surgical embolectomy is the preferred therapy; catheter-based interventions are alternatives when surgery is unavailable 1