Which anti-phospholipid syndrome (APS) tests can yield false-positive results in the context of a recent thrombosis?

Antiphospholipid Syndrome Tests That Can Yield False-Positive Results After Recent Thrombosis

Lupus anticoagulant (LA) testing is the most likely to yield false-positive results in the context of a recent thrombosis, especially when performed while the patient is on anticoagulant therapy. 1, 2

Impact of Recent Thrombosis on APS Testing

Lupus Anticoagulant (LA) Testing

• Most susceptible to interference from:
  • Acute phase reactants during thrombotic events 2
  • Anticoagulant medications commonly started after thrombosis 1, 2
  • Heparin, direct oral anticoagulants, and vitamin K antagonists can all interfere with LA testing 1

Anticardiolipin Antibodies (aCL)

• Less affected by acute thrombosis than LA
• IgM isotype more prone to transient positivity during inflammatory states 2
• Low-medium positive aCL IgM with negative LA has minimal association with thrombotic risk 2

Anti-β2-glycoprotein I Antibodies (aβ2GPI)

• Generally more specific and less affected by acute thrombotic events
• More stable during acute events compared to LA testing 1

Testing Recommendations After Thrombosis

Timing of Testing

• Ideally collect blood before starting anticoagulant therapy 1
• If not possible, consider the following:
  • For patients on heparin: Ensure blood collection when heparin levels are minimal
  • For patients on warfarin: Interpret LA results with caution; consider factor-specific assays in selected cases 3
  • For patients on DOACs: Consider temporary discontinuation if clinically safe, or note potential interference 2

Sample Processing

• Double centrifugation of blood samples is required 1
• Fresh venous blood in 0.109 M sodium citrate (9:1 ratio) 1
• Process quickly or freeze plasma if testing is postponed 1

Confirming Diagnosis

Essential Follow-up Testing

• Repeat testing >12 weeks after initial positive result to confirm persistence 1, 2
• This is critical as transient positivity during acute thrombosis is common 1
• Triple positivity (LA, aCL, and aβ2GPI) carries the highest thrombotic risk 1

Risk Stratification

• Single positive test results, especially isolated aCL IgM, should be interpreted with caution 2
• Multiple positive tests, particularly with IgG isotype or high titers, indicate higher risk 2
• LA positivity is the strongest predictor for thrombotic events 1

Common Pitfalls to Avoid

• Testing only once without confirming persistence after 12 weeks 1, 2
• Overinterpreting isolated positive results, especially during acute thrombosis 2
• Failing to consider the interference of anticoagulants with LA testing 1, 3
• Not performing a complete antibody profile (LA, aCL IgG/IgM, aβ2GPI IgG/IgM) 2
• Making treatment decisions based on tests performed during acute thrombotic events 2

By understanding these limitations and following proper testing protocols, clinicians can avoid misdiagnosis and inappropriate long-term anticoagulation in patients with false-positive APS test results following a recent thrombosis.