For a 12-year-old patient with acute ischemic stroke and no traditional atherosclerotic risk factors, is testing for protein C and S and aspirin (acetylsalicylic acid) therapy warranted?

Testing for Protein C and S and Aspirin Use in Pediatric Acute Ischemic Stroke

Direct Answer

In a 12-year-old with acute ischemic stroke, testing for protein C and S deficiency is reasonable given the young age and presumed absence of traditional atherosclerotic risk factors, but testing should be deferred until at least 4-6 weeks after the acute event to avoid false-positive results. Aspirin therapy (160-325 mg within 24-48 hours, then 75-100 mg daily) should be initiated after hemorrhage is excluded by neuroimaging, unless the patient receives thrombolytic therapy, in which case aspirin must be delayed for 24 hours. 1, 2, 3

Rationale for Thrombophilia Testing in Young Stroke Patients

When to Consider Testing

• Hypercoagulable states should be considered in younger populations with no identifiable cause for stroke, particularly with self- or family history of unprovoked thrombosis. 1

• In pediatric and young adult stroke patients without traditional atherosclerotic risk factors, inherited thrombophilias including protein C and S deficiency represent potential etiologies that warrant investigation. 1

• The key caveat: protein C, protein S, and antithrombin levels may be artificially altered during the acute stroke phase, so testing should be deferred or repeated at least 4-6 weeks after the acute event. 1

Evidence Supporting Testing in Young Patients

• Case series have documented that deficiencies in protein C and protein S can cause cerebral arterial thrombosis in young adults, with one study finding 17% of stroke patients under age 45 had deficiencies in these coagulation inhibitors. 4

• Combined deficiencies of protein C and S may represent particularly high risk factors for ischemic stroke in young adults. 5

• However, a 2018 study found that thrombophilia testing was positive in only 14% of young stroke/TIA patients overall, with primary protein C, S, or antithrombin deficiency found in only 2.8% of tested patients. 6

Clinical Significance

• Low protein C levels in acute stroke may reflect massive activation of coagulation factors and predict adverse outcomes, though this represents an acute-phase reactant rather than a primary deficiency. 7

• The diagnostic yield of routine thrombophilia screening remains modest even in young patients, but the potential for identifying a treatable hereditary condition justifies selective testing in this age group. 6

Aspirin Administration Guidelines

Timing and Dosing

• Aspirin (160-325 mg) should be initiated within 24-48 hours of stroke onset after CT/MRI has excluded hemorrhage. 2, 3

• For long-term secondary prevention, lower doses (75-100 mg daily) have similar efficacy with fewer gastrointestinal side effects. 2

Critical Contraindications

• Aspirin must NOT be administered within 24 hours of thrombolytic therapy (rtPA) due to increased bleeding risk. 2, 3

• If thrombolysis is given, aspirin should be delayed until 24 hours after treatment and after repeat imaging excludes hemorrhage. 3

• Aspirin should not be used as a substitute for thrombolytic therapy in eligible patients. 2

Evidence for Aspirin in Acute Stroke

• Combined analysis of 40,000 patients from CAST and IST trials demonstrated that early aspirin reduces recurrent ischemic stroke by 7 per 1,000 patients and overall stroke or death by 9 per 1,000, with only a 2 per 1,000 increase in hemorrhagic complications. 8

• The primary benefit of early aspirin is reduction of early recurrent stroke rather than limitation of neurological consequences of the initial stroke itself. 1, 2

• This benefit applies across age groups, though the specific evidence in pediatric populations is limited. 8

Practical Algorithm for This Patient

1. Immediate management: Obtain urgent CT/MRI to exclude hemorrhage 3

2. Aspirin initiation: If hemorrhage excluded and no thrombolysis given, start aspirin 160-325 mg within 24-48 hours 2, 3

3. Thrombophilia workup timing: Defer protein C and S testing until 4-6 weeks post-stroke to avoid false results from acute-phase changes 1

4. Additional considerations: Evaluate for other hypercoagulable states including antiphospholipid antibodies, particularly if there is history of thrombosis or family history of clotting disorders 1

5. Long-term management: Transition to aspirin 75-100 mg daily for secondary prevention 2

Important Caveats

• The absence of traditional atherosclerotic risk factors in a 12-year-old makes alternative etiologies including hypercoagulable states, cardiac sources, arterial dissection, and vasculopathy more likely and warrants comprehensive evaluation beyond just protein C and S. 1

• Follow-up of abnormal thrombophilia results is often poor in clinical practice, so ensure a clear plan for confirmatory testing and genetic counseling if initial results are abnormal. 6

• Even if protein C or S deficiency is identified, the primary acute management remains antiplatelet therapy unless specific criteria for anticoagulation are met (such as confirmed antiphospholipid syndrome or paradoxical emboli from venous thrombosis). 1