What are the contraindications for streptokinase?

Streptokinase Contraindications

Streptokinase has both general fibrinolytic contraindications and unique contraindications specific to its antigenic properties, most critically including absolute contraindication to re-administration within 6 months of prior exposure due to persistent neutralizing antibodies that cause serious allergic reactions and render the drug ineffective. 1, 2

Absolute Contraindications

General Fibrinolytic Contraindications (Apply to All Thrombolytics Including Streptokinase)

• Any prior intracranial hemorrhage or stroke of unknown origin at any time 1
• Known structural cerebral vascular lesion (e.g., arteriovenous malformation) 1
• Known malignant intracranial neoplasm (primary or metastatic) 1
• Ischemic stroke within 3-6 months (ACC/AHA specifies 3 months, ESC specifies 6 months) 1
  • Exception: Acute ischemic stroke within 3-4.5 hours may be treated with fibrinolytics 1
• Suspected aortic dissection 1
• Active bleeding or bleeding diathesis (excluding menses) 1
• Significant closed-head or facial trauma within 3 weeks 1
• Intracranial or intraspinal surgery within 2 months 1
• Recent major trauma/surgery/head injury within 3 weeks 1
• Gastrointestinal bleeding within the past month 1
• Non-compressible punctures in the past 24 hours (e.g., liver biopsy, lumbar puncture) 1

Streptokinase-Specific Absolute Contraindications

The most critical distinction for streptokinase is its high antigenicity, which creates unique contraindications not applicable to fibrin-specific agents like alteplase, reteplase, or tenecteplase. 1, 2

• Prior treatment with streptokinase within the previous 6 months - This is classified as an absolute contraindication by ACC/AHA guidelines due to development of persistent neutralizing antibodies that can cause serious allergic reactions and impair drug activity 1, 2, 3
• Prior allergic reaction to streptokinase or anistreplase (APSAC) - Any history of allergic reaction absolutely contraindicates re-exposure 1, 3
• Prior exposure to anistreplase (APSAC) within 6 months - APSAC contains streptokinase and shares the same antigenic properties 2
• History of hemorrhagic stroke 1
• Recent cranial trauma or neoplasm 1
• Blood pressure >200/120 mm Hg 1
• Diabetic hemorrhagic retinopathy 1

Relative Contraindications

General Fibrinolytic Relative Contraindications

• History of chronic, severe, poorly controlled hypertension 1
• Severe uncontrolled hypertension on presentation (SBP >180 mm Hg or DBP >110 mm Hg) 1
• History of prior ischemic stroke >3 months 1
• Transient ischemic attack in the preceding 6 months 1
• Dementia or known intracranial pathology not covered in absolute contraindications 1
• Traumatic or prolonged CPR (>10 minutes) 1
• Major surgery within 2-3 weeks 1
• Recent internal bleeding (within 2-4 weeks) 1
• Non-compressible vascular punctures 1
• Pregnancy or within 1 week postpartum 1
• Active peptic ulcer 1
• Oral anticoagulant therapy - The higher the INR, the higher the bleeding risk 1

Streptokinase-Specific Relative Contraindications

• Recent gastrointestinal bleeding (within 10 days) 1
• Recent puncture of non-compressible vessels (within 10 days) 1
• Recent non-hemorrhagic stroke (within 2 months) 1
• Infective endocarditis 1
• Large thrombus in left atrium or on prosthesis 1
• Recent major operation or trauma (within 2 weeks) 1
• Known bleeding diathesis 1

Critical Clinical Considerations

The 6-Month Re-administration Rule

This is the most important streptokinase-specific contraindication that distinguishes it from fibrin-specific agents. Streptokinase triggers a robust immune response leading to development of antistreptokinase antibodies that persist for at least 6 months. 1, 2, 3 Re-administration during this period can cause:

• Serious allergic reactions including anaphylaxis 2, 3, 4, 5
• Drug ineffectiveness due to antibody neutralization 1, 2
• Hypotension (though severe allergic reactions are rare with first exposure) 1

Alternative Agents When Streptokinase is Contraindicated

If thrombolysis is needed after prior streptokinase exposure or in patients with streptokinase allergy, use fibrin-specific agents instead: 2, 3

• Alteplase (tPA) - Non-antigenic, safe for repeat dosing 2, 3
• Reteplase (rPA) - Non-antigenic, double-bolus administration 2, 3
• Tenecteplase (TNK-tPA) - Non-antigenic, single weight-based bolus 2, 3

These agents do not cause antibody formation and can be safely re-administered without the 6-month restriction. 2, 3

Management of Allergic Reactions During Infusion

If urticaria and itching develop during streptokinase infusion without hemodynamic instability: 3

• Slow the infusion rate and administer antihistamines 3
• Do not re-administer streptokinase if it was stopped due to allergic reaction - the patient is now sensitized 3
• Switch to fibrin-specific agents (tenecteplase, alteplase, or reteplase) if continued thrombolysis is needed 3
• Consider urgent transfer for rescue PCI if fibrinolysis fails or is contraindicated 3

Common Pitfalls to Avoid

• Do not assume all thrombolytics have the same contraindications - Streptokinase's antigenicity creates unique restrictions not applicable to tPA-based agents 1, 2
• Do not use streptokinase in acute ischemic stroke - Studies show increased mortality with streptokinase in this setting 6
• Do not overlook the timing of prior streptokinase exposure - Always ask about any thrombolytic use in the past 6 months 1, 2
• Successful resuscitation does not contraindicate fibrinolysis, but prolonged or traumatic resuscitation is a relative contraindication 1