What condition would exclude a patient from receiving alteplase?

October 11, 2025 •

3 min read

According to the American Heart Association and American Stroke Association guidelines, one of the most critical exclusion criteria for alteplase (tissue plasminogen activator, tPA) is any sign of a current intracranial hemorrhage. This medication is a powerful thrombolytic, and its administration is based on a careful and rapid risk-benefit analysis, making it essential to identify what condition would exclude a patient from receiving alteplase before treatment.

Quick Summary

This article examines the primary contraindications for alteplase, including recent bleeding, severe hypertension, and intracranial issues, and outlines the varying exclusion criteria depending on the medical emergency. It discusses the critical safety considerations, highlighting how a patient's history and current health status determine eligibility for this life-saving but high-risk medication.

Key Points

Intracranial Hemorrhage: The presence of an intracranial bleed on a CT scan is a firm absolute contraindication for alteplase.
Bleeding Disorders and Risk: A history of bleeding diathesis, active internal bleeding, or recent trauma/surgery significantly increases the risk of hemorrhage with alteplase.
Recent Intracranial Events: Having an ischemic stroke, serious head trauma, or intracranial/intraspinal surgery within the last 3 months typically excludes a patient from receiving alteplase.
Blood Pressure Control: Uncontrolled severe hypertension (BP >185/110 mmHg) is a major exclusion criterion due to the high risk of hemorrhagic stroke.
Intracranial Pathologies: The presence of intracranial neoplasms (tumors) or vascular malformations like AVMs and aneurysms makes alteplase use too dangerous.
Timeliness of Treatment: For ischemic stroke, alteplase is only effective and indicated within a specific time window, typically 3 to 4.5 hours from symptom onset.
Coagulation Status: Abnormal coagulation tests, potentially from anticoagulant use (warfarin, NOACs) or liver disease, can be a contraindication.
High-Risk Patients: Patients of advanced age (>80) or those with both diabetes and a prior stroke are often subject to additional scrutiny or different time windows for stroke treatment.

Understanding the Action of Alteplase

Alteplase, also known by its brand name Activase, is a thrombolytic medication that works by converting plasminogen into plasmin, an enzyme that dissolves blood clots. This mechanism makes it highly effective for treating conditions caused by blood clots, such as acute ischemic stroke, massive pulmonary embolism, and certain cases of acute myocardial infarction. However, the very nature of its action—dissolving clots—introduces a significant risk of hemorrhage, or uncontrolled bleeding. For this reason, a comprehensive list of contraindications, or conditions that exclude a patient from receiving alteplase, must be thoroughly evaluated before administration to ensure patient safety.

Absolute Contraindications: A Firm 'No'

Absolute contraindications are conditions where the risk of administering alteplase is so high that the medication must not be given under any circumstances. The most critical absolute contraindications relate to situations with an immediate and life-threatening risk of bleeding, especially in the brain. The discovery of intracranial hemorrhage on a CT scan is a primary example because alteplase could drastically worsen the bleed and cause fatal outcomes.

Other absolute contraindications, particularly for treating ischemic stroke, include:

Intracranial Hemorrhage
History of Intracranial Hemorrhage
Recent Intracranial or Intraspinal Surgery (within the last three months)
Serious Head Trauma (within the last three months)
Intracranial Neoplasm or AVM
Active Internal Bleeding
Severe Uncontrolled Hypertension (>185/110 mmHg)
Known Bleeding Diathesis (e.g., low platelet count or coagulation abnormalities)

Relative Contraindications: A Careful Risk Assessment

Relative contraindications require a careful balancing of the potential benefits of alteplase against the heightened risks. In some emergency situations, such as a life-threatening pulmonary embolism, a healthcare provider might determine that the immediate benefit of dissolving a large, dangerous clot outweighs the increased risk of a potential hemorrhage.

Relative contraindications can vary depending on the specific medical emergency being treated. Factors such as recent major surgery or trauma, recent stroke, severe liver disease, pregnancy, advanced age, use of oral anticoagulants, or rapidly improving/minor stroke symptoms all necessitate a thorough evaluation.

A Comparison of Alteplase Contraindications


Condition	Absolute Contraindication for Ischemic Stroke	Absolute Contraindication for PE/AMI	Relative Contraindication for All Indications
Current Intracranial Hemorrhage	Yes	Yes (Any)	No
Previous Intracranial Hemorrhage	Yes	Yes	No
Severe Uncontrolled Hypertension (>185/110 mmHg)	Yes	Yes	Yes (if controlled)
Active Internal Bleeding	Yes	Yes	No
Recent Intracranial/Intraspinal Surgery (< 3 months)	Yes	Yes	No
Major Surgery (< 14 days to 3 weeks)	No (Relative)	No (Relative)	Yes
Recent Stroke (< 3 months)	Yes	Yes	No
History of Intracranial Neoplasm or AVM	Yes	Yes	No
Severe Platelet Count (<100,000)	Yes	Yes (Bleeding diathesis)	No
Pregnancy	No (Relative)	No (Relative)	Yes

The Critical Role of Timing and Assessment

A non-contrast head CT scan is a vital initial step for suspected ischemic stroke patients to rule out intracranial hemorrhage, which is an immediate exclusion for alteplase. The timing of symptom onset is also critical for ischemic stroke, with treatment typically administered within 3 to 4.5 hours. The assessment for contraindications is an ongoing process that includes reviewing medical history, performing a physical examination, and conducting laboratory tests to identify risks like recent trauma, gastrointestinal bleeding, or the use of anticoagulant medications. Ultimately, the decision to use alteplase is a complex one, made by experienced medical professionals who carefully weigh the risks and potential benefits in acute, life-threatening situations.

Conclusion

Administering alteplase requires a careful evaluation of risks and benefits based on medical exclusion criteria. The most significant reason for exclusion is the presence of an intracranial hemorrhage. However, other absolute contraindications, such as recent surgery, trauma, and pre-existing intracranial conditions, also prevent its use due to the high risk of severe bleeding. Relative contraindications, including recent stroke, advanced age, and pregnancy, necessitate a detailed, individual assessment. A rapid and thorough evaluation of a patient's medical history and current condition is crucial to determine their eligibility and safety for this powerful medication.

External Resource

For additional professional guidelines and resources on alteplase administration, a valuable source is the National Institute of Neurological Disorders and Stroke (NINDS).

Frequently Asked Questions

A non-contrast head CT scan is a critical first step to differentiate between an ischemic stroke (caused by a clot) and a hemorrhagic stroke (caused by a bleed). Administering alteplase to a patient with a hemorrhagic stroke would dangerously worsen the bleeding and is absolutely contraindicated.

Generally, patients on anticoagulants like warfarin or NOACs are excluded from alteplase treatment, especially if their coagulation tests are abnormal (e.g., INR > 1.7). However, the specific drug and timing of the last dose are carefully evaluated, and new guidelines might allow exceptions with normal lab tests.

Severe uncontrolled hypertension is defined as a systolic blood pressure greater than 185 mmHg or a diastolic pressure greater than 110 mmHg. If a patient's blood pressure cannot be lowered below these levels with medication, they are excluded from alteplase treatment due to the high risk of intracranial hemorrhage.

Minor or rapidly improving stroke symptoms are often considered a relative contraindication. The decision depends on the potential for disability and the healthcare provider's judgment, as even mild deficits can become debilitating. For some time windows, it can be an exclusion criterion.

Alteplase must be initiated as soon as possible after symptom onset, typically within 3 to 4.5 hours for eligible patients, to maximize effectiveness and minimize risk. The therapeutic window is tight, and delayed administration increases risks and reduces benefits.

If the time of symptom onset is unknown (e.g., a patient wakes up with symptoms), this typically excludes them from standard alteplase treatment. Specialized imaging may be used in some settings to determine eligibility, but it remains a complex scenario.

Yes, for a pulmonary embolism, a history of a recent stroke is a contraindication. Specific guidelines also apply for factors like pregnancy, certain blood pressure levels, and recent surgery.