What is the risk of stroke in patients with Antiphospholipid Syndrome (APS) and how is it managed?

Risk of Stroke in Antiphospholipid Syndrome and Management Strategies

Patients with Antiphospholipid Syndrome (APS) have a significantly increased risk of stroke, and warfarin anticoagulation with a target INR of 2-3 is the recommended treatment for secondary stroke prevention in these patients. 1

Stroke Risk in APS

Antiphospholipid syndrome is characterized by:

• Persistent presence (testing 12 weeks apart) of lupus anticoagulant, anticardiolipin antibodies, or anti-β2 glycoprotein-I antibodies
• Clinical manifestations including vascular thrombosis or pregnancy morbidity 1

The risk of stroke is particularly elevated in:

• Young patients (<55 years of age) 1
• Patients with triple-positive antibody status (lupus anticoagulant, anticardiolipin, and anti-β2 glycoprotein-I) 1
• Patients with previous thrombotic events 1

Diagnostic Considerations

Testing for APS should be considered in:

• Young stroke patients without traditional risk factors
• Patients with history of:
  • Venous thromboembolism
  • Second-trimester abortion
  • Rheumatologic disorders 1
• Patients with unexplained recurrent thrombotic events

Cardiac evaluation is essential as:

• Transesophageal echocardiogram is strongly recommended due to high prevalence of valvular abnormalities that could be sources of cardiogenic embolism 2
• Cardiac valve involvement is common in patients with anticardiolipin antibodies 3

Management of Stroke Risk in APS

For patients with positive antiphospholipid antibodies but no clinical APS:

• Antiplatelet therapy alone is recommended for those with a single positive antiphospholipid antibody but who do not fulfill criteria for APS 1

For patients with confirmed APS and stroke/TIA:

• Warfarin anticoagulation with a target INR of 2-3 is reasonable to reduce the risk of recurrent stroke or TIA 1
• Higher intensity anticoagulation (INR >3) is not recommended as it increases bleeding risk without providing additional thrombotic protection 1

Important caution regarding DOACs:

• Rivaroxaban is NOT recommended for patients with APS, especially those with triple-positive antibodies, due to excess thrombotic events compared to warfarin 1
• Other DOACs should generally be avoided in APS patients until ongoing trials clarify whether the increased thrombosis risk is a class effect or specific to rivaroxaban 1

Special Considerations

Multidisciplinary approach:

• Collaboration between neurology, hematology, and rheumatology is beneficial 4
• Management of conventional cardiovascular risk factors is important as they can compound stroke risk in APS patients 4

Beyond stroke:

• APS can cause a wider spectrum of cerebrovascular manifestations including:
  • White matter hyperintensities
  • Cortical atrophy
  • Multiple infarcts
  • Cognitive impairment 4

Common Pitfalls to Avoid

1. Misdiagnosis: Ensure proper testing with repeat antibody measurements 12 weeks apart before confirming APS diagnosis 1

2. Inappropriate anticoagulation: Using DOACs, particularly rivaroxaban, instead of warfarin in APS patients with stroke 1

3. Inadequate INR monitoring: Maintaining the target INR of 2-3 is crucial; both under- and over-anticoagulation increase risks 1

4. Overlooking cardiac sources: Failing to perform thorough cardiac evaluation, particularly transesophageal echocardiography 2

5. Neglecting other risk factors: Not addressing modifiable conventional cardiovascular risk factors that may compound stroke risk in APS patients 4