Fibrinolytic Therapy (Thrombolytic Therapy) Topic Review

Introduction

Fibrinolytic therapy, also known as thrombolytic therapy, is used to lyse acute blood clots by activating plasminogen, resulting in the formation of plasmin, which cleaves the fibrin cross-links causing thrombus breakdown.

Names

tPA (tissue plasminogen activator), alteplase, reteplase, streptokinase, tenecteplase, urokinase

Indications

Fibrinolytic therapy is used in the treatment of a ST segment elevation myocardial infarction (STEMI), acute stroke and other less common indications such as pulmonary embolism and acute deep venous thrombosis.

During STEMI, fibrinolytic therapy must be instituted within 24 hours of symptom onset. After this time frame, fibrinolytic therapy is contraindicated and likely will not be effective. Note that fibrinolytic therapy is always given simultaneously with anticoagulation using unfractionated heparin or low molecular weight heparin.

Contraindications

When the decision to treat a patient experiencing a STEMI with fibrinolytic therapy is made, because primary PCI is not available in a timely fashion, contraindications must be considered; suspected aortic dissection, active bleeding (excluding menses) or a bleeding diathesis are contraindications to fibrinolytic therapy.

Generally, if there is high risk for intracranial hemorrhage (ICH), defined as greater than 4%, fibrinolytic therapy is contraindicated as well, and primary PCI is preferred (class I).

The following would place a patient in the high-risk category for ICH:

1. Prior intracranial hemorrhage
2. Ischemic stroke within 3 months
3. Known cerebrovascular abnormality such as aneurysm or arteriovenous malformation
4. Known malignant intracranial tumor
5. Significant closed-head trauma or facial trauma within 3 months

Relative contraindications (not absolute) to fibrinolytic therapy include:

1. Uncontrolled hypertension (BP > 180/110), either currently or in the past
2. Intracranial abnormality not listed as absolute contraindication (i.e. benign intracranial tumor)
3. Ischemic stroke more than 3 months prior
4. Bleeding within 2 to 4 weeks (excluding menses)
5. Traumatic or prolonged cardiopulmonary resuscitation
6. Major surgery within 3 weeks
7. Pregnancy
8. Current use of anticoagulants
9. Non-compressible vascular puncture
10. Dementia

Note that advanced age is not listed as an absolute or relative contraindication to fibrinolytic therapy in the American College of Cardiology/American Heart Association guidelines.

Miscellaneous

Streptokinase is immunogenic; once exposed, a repeat exposure can cause severe allergic reactions including anaphylaxis, and thus is not recommended.