Can a patient with a lacunar infarct and possible comorbidities such as hypertension, diabetes, or previous strokes undergo thrombolysis with alteplase (tissue plasminogen activator)?

Thrombolysis for Lacunar Infarct

Yes, patients with lacunar infarct should receive IV alteplase if they meet standard eligibility criteria and present within the appropriate time window, as lacunar strokes benefit equally from thrombolysis compared to other ischemic stroke subtypes. 1, 2

Evidence Supporting Thrombolysis in Lacunar Stroke

The American College of Chest Physicians recommends IV alteplase (0.9 mg/kg, maximum 90 mg) for acute ischemic stroke within 3 hours (Grade 1A) or within 4.5 hours (Grade 2C) of symptom onset, without excluding lacunar strokes. 1 The Canadian Stroke Best Practice guidelines similarly recommend alteplase at 0.9 mg/kg with 10% as bolus over one minute and 90% infused over 60 minutes, applicable to all ischemic stroke types including lacunar infarcts. 1

Clinical Outcomes Data

• Patients with lacunar strokes benefit approximately equally from thrombolysis compared to those with partial anterior circulation stroke and total anterior circulation strokes, based on analysis of 11,503 ischemic stroke patients from the Canadian Stroke Network Registry. 2

• In the recent AcT trial (2025), patients with lacunar infarct who received thrombolysis had better safety profiles and functional outcomes compared to the overall trial population, with zero cases of symptomatic intracerebral hemorrhage among 93 lacunar stroke patients versus 2.3% in nonlacunar infarcts. 3

• Thrombolysis shows significant association with improved modified Rankin Scale scores at discharge and higher rates of discharge to home in lacunar stroke patients, after controlling for stroke subtypes. 2

Addressing Common Misconceptions

The "No Visible Occlusion" Concern

The historical debate about thrombolysing lacunar strokes centered on two flawed assumptions: that lacunar strokes are uniformly benign and that absence of visible large vessel occlusion means no thrombosis exists. 4 However:

• Lacunar stroke carries unfavorable long-term prognosis with increased risk of death, recurrent stroke, and cognitive dysfunction, contradicting the "benign" characterization. 4

• The absence of visible occlusion on CT angiography does not negate the presence of small vessel thrombosis or the potential benefit of thrombolysis. 3

• Among patients with no visible occlusion, those with lacunar infarct had similar safety profiles to those with no visible infarct, and both groups had better outcomes than the overall trial population. 3

Standard Treatment Protocol

Time Windows and Dosing

• Within 3 hours of symptom onset: Strong recommendation (Grade 1A) for IV alteplase 1

• Between 3-4.5 hours: Conditional recommendation (Grade 2C) for IV alteplase 1

• Beyond 4.5 hours: Thrombolysis is not recommended (Grade 1B) 1

• Dose: 0.9 mg/kg (maximum 90 mg total), with 10% given as IV bolus over 1 minute, remaining 90% infused over 60 minutes 1

Blood Pressure Management

Blood pressure must be lowered to <185/110 mmHg before initiating IV alteplase and maintained ≤180/105 mmHg after administration. 5, 6

Comorbidities Are Not Contraindications

The presence of hypertension, diabetes, or previous stroke does not exclude lacunar stroke patients from thrombolysis:

• Patients with combined history of prior stroke and diabetes mellitus showed favorable outcomes with alteplase (adjusted OR 1.50,95% CI 1.03-2.18) in a comprehensive analysis of 9,613 patients. 7

• Thrombolysis benefits patients irrespective of age, gender, and presence of comorbid conditions such as diabetes mellitus, though degree of benefit varies. 1

• Patients aged >80 years showed adjusted OR of 1.40 (95% CI 1.14-1.70) for favorable outcomes with alteplase treatment. 7

Small Vessel Disease Considerations

White Matter Lesions and Microbleeds

Neuroimaging evidence of small vessel disease (white matter lesions, cerebral microbleeds) increases the risk of intracerebral hemorrhage during thrombolysis but does not represent an absolute exclusion criterion. 4

• The presence of cerebral small vessel disease should prompt careful risk-benefit assessment but should not automatically exclude patients from treatment. 4

• Thrombolysis remains an effective treatment in acute lacunar stroke even when small vessel disease is present. 4

Special Circumstances

Early Recurrent Lacunar Stroke

Intravenous thrombolysis may be safe for early recurrent lacunar stroke in patients with relatively small hemorrhage risk, as demonstrated in a case where alteplase was successfully administered 7 days after a previous lacunar infarct. 8

Mild or Rapidly Improving Symptoms

Withholding thrombolysis because of mild or improving symptoms may not be justified, as approximately one-third of acute stroke patients with rapid improvement develop severe subsequent deterioration. 1 Post-hoc analysis from NINDS showed no difference in beneficial effects of alteplase in patients with minor stroke syndromes compared to the overall cohort. 1

Critical Safety Monitoring

Post-thrombolysis monitoring requires:

• Admission to intensive care or stroke unit 6
• Neurological assessments every 15 minutes during and for 2 hours after infusion, then every 30 minutes for 6 hours, then hourly until 24 hours 6
• Blood pressure monitoring to maintain ≤180/105 mmHg 6

Key Pitfall to Avoid

Do not delay or withhold IV alteplase in lacunar stroke patients to obtain CT angiography or because no large vessel occlusion is visible. 6 The absence of visible occlusion on vascular imaging does not negate the benefit of thrombolysis in lacunar infarcts. 3, 2