What Major Conditions Exclude Patients from Reperfusion Therapy with Alteplase?

Alteplase, also known as tissue plasminogen activator (tPA), is a critical, time-sensitive medication used to dissolve dangerous blood clots in conditions like acute ischemic stroke, massive pulmonary embolism, and acute myocardial infarction. However, administering this potent thrombolytic is not without significant risk, and several major conditions exclude patients from reperfusion therapy with alteplase due to an unacceptable risk of severe, often fatal, bleeding.

Quick Summary

This article details the absolute and relative contraindications for alteplase, covering high-risk scenarios such as intracranial bleeding, recent surgery or trauma, existing medical conditions like uncontrolled hypertension or bleeding disorders, and specific timing issues.

Key Points

• Intracranial Hemorrhage: Any prior or current intracranial bleeding, including stroke or trauma, is an absolute contraindication for alteplase due to the risk of re-bleeding.

• Recent Surgery or Trauma: Surgery involving the brain or spine within 3 months, or recent serious head trauma, makes alteplase administration prohibitively risky.

• Coagulation Disorders: Pre-existing bleeding disorders (diathesis) or laboratory evidence of coagulation abnormalities (e.g., high INR, low platelets) are major exclusion criteria.

• Severe Uncontrolled Hypertension: Patients with severely elevated blood pressure (>185/110 mmHg) that cannot be controlled should not receive alteplase due to the risk of intracranial hemorrhage.

• Recent Anticoagulant Use: For ischemic stroke, recent use of oral anticoagulants, especially with elevated lab values, is a significant contraindication.

• Risk vs. Benefit: Relative contraindications, such as recent major surgery or advanced age, require a careful, individualized risk-benefit assessment by a clinician.

• Alternative Therapies: In patients where alteplase is contraindicated, alternative reperfusion strategies like mechanical thrombectomy may be available and effective.

Alteplase (Activase) works by converting plasminogen to plasmin, an enzyme that breaks down fibrin clots. While effective in treating acute thrombotic events, its use carries a primary risk of hemorrhage. Patient screening for factors increasing bleeding risk is crucial. These factors are categorized as absolute or relative contraindications.

Absolute Contraindications: Non-negotiable Exclusions

Absolute contraindications mean alteplase must be withheld due to extremely high risk. Key examples include active or recent intracranial hemorrhage, suspected subarachnoid hemorrhage, recent intracranial or intraspinal surgery or serious head trauma within 3 months, active internal bleeding, and known bleeding diathesis or coagulation abnormalities. Intracranial neoplasms or vascular malformations, severe uncontrolled hypertension, and recent oral anticoagulant use (for stroke) are also contraindications.

Relative Contraindications: Balancing Risk vs. Benefit

Relative contraindications require careful consideration of benefits versus increased bleeding risk. These include recent major surgery or trauma within a specific timeframe, recent gastrointestinal or urinary tract hemorrhage within the previous 21 days, pregnancy, recent myocardial infarction within the preceding 3 months, acute pericarditis, subacute bacterial endocarditis, and advanced age.

Comparison of Absolute vs. Relative Contraindications

Condition Type	Absolute Contraindications	Relative Contraindications	Decision-Making Process
Hemorrhage	Current Intracranial Hemorrhage (ICH), Subarachnoid Hemorrhage (SAH), Active Internal Bleeding	Recent (within 21 days) GI or GU bleeding, Recent Cerebrovascular Disease	Absolute exclusion, unless time-sensitive endovascular therapy is possible.
Trauma/Surgery	Recent (<3 months) Intracranial/Spinal surgery, Serious head trauma	Recent (within 14-21 days) major surgery or serious trauma	Non-negotiable exclusion for absolute criteria; individualized risk-benefit for relative.
Pre-existing Vascular Conditions	Known Intracranial Neoplasm, Arteriovenous Malformation (AVM), or Aneurysm	History of cerebral hemorrhage (varies by guidelines and imaging)	Absolute exclusion due to high risk of bleeding.
Blood Pressure	Severe uncontrolled hypertension (e.g., >185/110 mmHg)	Chronic, severe, poorly controlled hypertension	Attempt to control BP immediately for absolute; careful assessment for relative.
Blood Disorders	Known Bleeding Diathesis, significant thrombocytopenia (<100,000/mm³), or elevated coagulation labs (INR >1.7)	Specific minor bleeding disorders (may not be excluded)	Non-negotiable exclusion due to high risk of systemic bleeding.

Alternatives to Alteplase for Reperfusion

When alteplase is contraindicated, alternative reperfusion strategies are available. For acute ischemic stroke with large vessel occlusion, mechanical thrombectomy can be highly effective. Newer thrombolytics like tenecteplase are also potential options. Catheter-directed therapies can be used for massive pulmonary embolism. The best approach depends on the individual patient, diagnosis, and time since symptom onset.

Conclusion

While alteplase is a vital treatment for thrombotic emergencies, its significant hemorrhagic risks necessitate careful screening. Identifying what major conditions exclude patients from reperfusion therapy with alteplase is critical to prevent severe bleeding. Understanding absolute and relative contraindications guides clinical decisions and ensures patient safety. Adhering to guidelines and using clinical judgment are paramount in determining the best course of action.

More information on this topic can be found through resources like the American Heart Association and the National Institutes of Health.

Frequently Asked Questions

Why is a recent stroke an exclusion criterion for alteplase?

For acute ischemic stroke, a prior stroke within the last 3 months is an exclusion criterion because it increases the risk of hemorrhagic conversion at the site of the older stroke, which could be catastrophic.

What is meant by 'active internal bleeding'?

Active internal bleeding refers to ongoing bleeding within the body, such as from the gastrointestinal tract, evidenced by bloody stool (melena) or other clinical signs. It is an absolute contraindication because alteplase would worsen the bleeding.

Can alteplase be given if a patient's blood pressure is high?

No, not if the blood pressure is severely uncontrolled (>185/110 mmHg). The elevated pressure must be lowered and stabilized before alteplase can be considered to reduce the risk of intracranial hemorrhage.

Are there different criteria for different conditions?

Yes. While many contraindications are shared across indications (like intracranial hemorrhage), some differ. For example, a recent stroke is an exclusion for pulmonary embolism treatment with alteplase, but the timeline differs for a repeat ischemic stroke.

What if a patient has a relative contraindication?

If a patient has a relative contraindication, a medical professional will weigh the potential benefits of reperfusion therapy against the increased risk of a serious complication, like bleeding. This requires careful clinical judgment and a case-by-case evaluation.

Is mechanical thrombectomy a possible alternative?

Yes, for certain types of acute ischemic stroke, particularly those with a large vessel occlusion, mechanical thrombectomy is an effective alternative to alteplase. It involves physically removing the clot and is often used when alteplase is contraindicated.

Does advanced age automatically exclude a patient from alteplase?

No, advanced age alone is not an absolute contraindication. However, it is considered a relative contraindication because older patients often have more comorbidities and a higher mortality rate. A thorough risk-benefit analysis is performed before administration.