Can a patient with liver malignancy who presents with an acute ischemic stroke receive intravenous alteplase (tissue plasminogen activator) if platelet count is ≥100 × 10⁹/L, INR ≤1.7, activated partial thromboplastin time is normal, there is no recent major surgery, no intracranial metastases, and no active internal bleeding?

Intravenous Alteplase in Acute Ischemic Stroke with Liver Malignancy

A patient with liver malignancy who presents with acute ischemic stroke and meets all standard eligibility criteria (platelet count ≥100 × 10⁹/L, INR ≤1.7, normal aPTT, no recent major surgery, no intracranial metastases, and no active bleeding) may reasonably receive intravenous alteplase, as systemic malignancy alone is not an absolute contraindication when life expectancy exceeds 6 months and other bleeding risk factors are absent. 1

Guideline Framework for Malignancy and Thrombolysis

The 2018 AHA/ASA guidelines explicitly address systemic malignancy as a relative contraindication rather than an absolute one. The guidelines state that "the safety and efficacy of alteplase in patients with current malignancy are not well established (Class IIb; LOE C-LD)," but importantly add that "patients with systemic malignancy and reasonable (>6 mo) life expectancy may benefit from IV alteplase if other contraindications such as coagulation abnormalities, recent surgery, or systemic bleeding do not coexist." 1

Critical Distinction: Liver vs. GI Malignancy

Liver malignancy is NOT listed among the absolute contraindications for alteplase. 1 The guidelines specifically contraindicate only:

• GI malignancy or GI bleeding within 21 days (Class III: Harm) 1, 2
• Intra-axial intracranial neoplasm (Class III: Harm) 1

Liver malignancy falls under the broader category of "systemic malignancy," which requires careful evaluation but is not an automatic exclusion. 1

Absolute Requirements Before Proceeding

Your patient must meet ALL of the following criteria before alteplase can be administered:

Coagulation Parameters (All Must Be Normal)

• Platelet count ≥100,000/mm³ 1, 2
• INR ≤1.7 1, 2
• aPTT ≤40 seconds 1, 2
• PT ≤15 seconds 1, 2

Exclusion of High-Risk Bleeding Sources

• No intracranial metastases (intra-axial brain tumors are Class III: Harm contraindication) 1
• No active internal bleeding 1
• No recent major surgery within 14 days 2
• No structural GI malignancy or GI bleeding within 21 days 1, 2

Additional Standard Contraindications

• Symptom onset ≤4.5 hours (or last known well ≤4.5 hours) 2, 3
• No intracranial hemorrhage on CT 2
• No extensive hypodensity (>1/3 MCA territory) 2, 3
• Blood pressure reducible to <185/110 mmHg 3

Evidence Supporting Treatment in Selected Cancer Patients

Multiple observational studies support the safety of alteplase in cancer patients when bleeding risk factors are absent:

• A 2013 case series of 11 patients with non-metastatic malignancy showed no severe hemorrhagic complications and 73% achieved favorable 3-month functional outcomes. 4
• A 2019 series of 5 patients with active malignancy treated with alteplase reported only one asymptomatic intracerebral hemorrhage and no systemic bleeding. 5
• These studies consistently excluded patients with metastatic disease, recent bleeding, coagulopathy, or anticoagulation. 4, 5

Important caveat: A 2017 Korean registry study found poor outcomes in cancer patients receiving alteplase (33% early neurological deterioration, 58% hemorrhagic transformation, 25% in-hospital mortality), particularly in cryptogenic stroke cases. 6 This underscores the importance of careful patient selection.

Decision Algorithm for Your Patient

Step 1: Verify Absolute Contraindications Are Absent

• Confirm no intracranial metastases on neuroimaging 1
• Confirm no active bleeding (no hematemesis, melena, hematuria, etc.) 1
• Verify no recent major surgery within 14 days 2
• Ensure liver malignancy has not caused GI bleeding within 21 days 1

Step 2: Confirm Laboratory Eligibility

• Platelet count ≥100,000/mm³ 1, 2
• INR ≤1.7 1, 2
• aPTT normal (≤40 seconds) 1, 2

Step 3: Assess Prognosis and Stroke Severity

• Estimate life expectancy >6 months from cancer 1
• Evaluate whether anticipated stroke disability outweighs bleeding risk 1
• Consider that severe strokes (NIHSS >25) may have poor outcomes regardless of treatment 3

Step 4: Proceed with Standard Alteplase Protocol

• Administer 0.9 mg/kg (maximum 90 mg) over 60 minutes with 10% as initial bolus 3
• Monitor for hemorrhagic complications during and after infusion 1

Critical Pitfalls to Avoid

Do not confuse liver malignancy with GI malignancy. Only structural GI malignancy or GI bleeding within 21 days is an absolute contraindication. 1, 2 Hepatocellular carcinoma or metastatic liver disease without GI involvement does not automatically preclude treatment.

Do not assume all cancer patients are ineligible. The guidelines explicitly allow treatment in selected patients with reasonable life expectancy and no additional bleeding risk factors. 1

Do not delay treatment for extensive cancer staging. If the patient meets standard eligibility criteria and has no evidence of intracranial metastases on acute stroke imaging, proceed with alteplase within the therapeutic window. 1, 3

Beware of occult coagulopathy. Liver malignancy can impair hepatic synthetic function, so verify that INR, PT, and platelet count are truly normal before initiating treatment. 1, 2