Thrombophilia Testing in Central Retinal Artery Occlusion
Thrombophilia testing should be considered only in select high-risk patients with CRAO, not routinely performed in all cases. 1
Primary Approach: Focus on Common Causes First
The etiological workup for CRAO should prioritize the most common mechanisms before considering thrombophilia testing 1:
- Embolic sources account for the vast majority of CRAO cases, with 71% of patients having ipsilateral carotid plaque 1
- Carotid imaging (CT/MR angiography or ultrasound) should be obtained urgently to identify high-grade stenosis requiring intervention 1
- Cardiac evaluation with transthoracic echocardiography is reasonable given the high rate of structural heart disease 1
- Cardiac rhythm monitoring for some duration is appropriate to screen for atrial fibrillation in patients without another clear cause 1
When to Consider Thrombophilia Testing
The American Heart Association specifically states that screening for hypercoagulable states should be reserved for select high-risk patients 1. Consider testing in:
- Young patients (typically <50 years old) without traditional atherosclerotic risk factors 2, 3
- Recurrent thrombotic events in the patient or strong family history of thrombosis 3
- Absence of identifiable embolic source after comprehensive cardiac and vascular evaluation 1
- Concurrent venous thromboembolism or other unusual thrombotic presentations 1
Evidence Regarding Thrombophilia in CRAO
While research demonstrates associations between thrombophilia and CRAO, the clinical utility remains limited:
- A 2023 study found at least one thrombophilic factor in 72% of CRAO patients, with antiphospholipid antibodies most common (38%) 2
- Protein C deficiency (33% vs 5%), hyperhomocysteinemia (22% vs 0%), and lupus anticoagulant (44% vs 12%) showed associations with CRAO 3
- However, the American Heart Association guidelines for stroke prevention note that hereditary hypercoagulable states like factor V Leiden and prothrombin mutations are not strongly associated with arterial stroke 1
Critical distinction: Thrombophilic conditions primarily increase risk for venous thromboembolism, not arterial occlusions like CRAO 1. The exception is when paradoxical embolism occurs through a patent foramen ovale 1.
Practical Testing Algorithm
If thrombophilia testing is pursued in high-risk patients, consider 2, 3:
- Antiphospholipid antibodies (lupus anticoagulant, anticardiolipin antibodies) - most relevant acquired thrombophilia 2, 3
- Homocysteine level - associated with both arterial and venous thrombosis 2, 3
- Protein C and protein S levels - if family history suggests inherited deficiency 2, 3
- Factor V Leiden - only if strong family history of venous thrombosis 2, 4
Common Pitfalls to Avoid
- Do not delay urgent stroke workup to pursue thrombophilia testing - CRAO requires immediate transfer to a stroke center within 24 hours 1
- Do not assume thrombophilia testing will change acute management - antiplatelet therapy and risk factor modification remain the cornerstone regardless of results 1
- Do not screen for thrombophilia in older patients (>50 years) with typical atherosclerotic risk factors - the yield is extremely low and will not alter management 1
- Do not overlook Giant Cell Arteritis in patients >50 years - this is the most important non-embolic cause requiring immediate high-dose corticosteroids 5, 6
Impact on Management
Even when thrombophilia is identified, treatment implications are limited:
- The APASS trial found no differential response between aspirin and warfarin in antiphospholipid antibody-positive stroke patients 1
- Long-term antiplatelet therapy with aspirin or clopidogrel is recommended for CRAO regardless of thrombophilia status 1
- Anticoagulation is reserved for specific indications like atrial fibrillation, not for isolated thrombophilia 1
The priority remains identifying treatable causes like carotid stenosis, cardiac sources, and Giant Cell Arteritis rather than pursuing extensive thrombophilia workups in most patients. 1