Is it warranted to request antinuclear antibody (ANA), erythrocyte sedimentation rate (ESR), protein C and S, antithrombin III, and homocysteine level in a pediatric patient with acute ischemic stroke?

Diagnostic Workup for Pediatric Stroke: Prothrombotic and Inflammatory Testing

Yes, comprehensive prothrombotic and inflammatory testing including ANA, ESR, protein C and S, antithrombin III, and homocysteine levels is warranted in pediatric stroke patients, as these tests help identify treatable causes and guide secondary prevention strategies.

Rationale for Testing

Prothrombotic Disorders

Children with stroke have an increased prevalence of prothrombotic abnormalities that independently contribute to stroke risk and recurrence. 1 In a prospective study of 162 children with ischemic stroke, 23% had cardiac disorders, and these children showed increased prevalence of prothrombotic abnormalities including elevated lipoprotein(a), anticardiolipin antibodies, and protein C deficiency compared to matched controls. 1 Importantly, stroke recurrence risk was significantly higher in children with one or more prothrombotic risk factors. 1

• Protein C, protein S, and antithrombin III deficiencies have been linked with stroke in case reports, and optimal screening requires both functional and antigenic assays. 2
• These inherited deficiencies represent potentially modifiable risk factors that can guide anticoagulation decisions. 2

Inflammatory and Autoimmune Markers

ESR and C-reactive protein are necessary in patients older than 50 years to screen for inflammation suggesting giant cell arteritis 1, though this applies primarily to adults. However, in pediatric populations:

• ANA testing helps identify antiphospholipid antibodies and lupus anticoagulants, which are the most frequently identified acquired prothrombotic states associated with ischemic stroke. 2
• Inflammatory processes can cause secondary vasculitis leading to pediatric stroke, with infectious etiologies being a leading cause. 3

Homocysteine

Hyperhomocysteinemia is associated with increased stroke risk, with prevalence varying by age and sex (29% in men aged 40-59 years, 21% in women aged 40-59 years). 1 While the risk reduction with treatment remains unknown 1, elevated homocysteine levels are significantly higher in acute stroke patients compared to controls. 4

Recommended Testing Protocol

Core Prothrombotic Panel

Special, step-wise screening for occult prothrombotic entities is recommended for:

• Young persons with stroke of uncertain cause
• Those with prior venous thrombosis
• Those with a family history of unusual thrombosis
• Those with no other explanation for recurrent stroke 2

The panel should include:

• Protein C (functional and antigenic assays) 2
• Protein S (functional and antigenic assays) 2
• Antithrombin III (functional and antigenic assays) 2
• Antiphospholipid antibodies/ANA 2
• Homocysteine level 1, 4

Inflammatory Markers

• ESR to screen for inflammatory processes 1
• C-reactive protein for acute phase response 1

Integration with Standard Stroke Workup

These tests should be obtained as part of routine blood work during the initial evaluation. 1 The standard pediatric stroke evaluation includes:

• Complete blood count with platelets
• Chemistry panel
• Hemoglobin A1C
• Prothrombin time and partial thromboplastin time
• Fasting lipid panel 1

Children with stroke should undergo comprehensive cardiac evaluation including echocardiography and detailed rhythm monitoring if clinically indicated. 1

Critical Timing Considerations

Evaluation should occur as soon as possible after onset of acute visual loss or neurological symptoms, with accelerated triage in an emergency center affiliated with a stroke center. 1 The therapeutic window for potential intervention extends up to 24 hours from last seen normal in pediatric stroke. 5

Common Pitfalls to Avoid

• Do not delay testing due to concerns about cost or yield - the contribution of prothrombotic diatheses to stroke is probably underrecognized. 2
• Ensure functional assays are performed, not just antigenic assays - inherited deficiencies require both for optimal screening. 2
• Repeat abnormal determinations - diagnosis of an anticoagulant protein deficiency has serious implications and should only be made on the basis of repeated abnormal determinations or documentation of the same deficiency in family members. 6
• Consider timing of testing - acute stroke and anticoagulation therapy can affect levels of these proteins, so interpretation must account for clinical context. 6