What do lupus inhibitors test for?

Lupus Anticoagulant Testing: Detection of Antiphospholipid Antibodies

Lupus anticoagulant (LA) tests detect antiphospholipid antibodies that interfere with phospholipid-dependent coagulation tests, which are associated with increased risk of thrombosis despite paradoxically prolonging in vitro clotting times. 1, 2

Recommended Testing Approach

Primary Testing Methods

• Dilute Russell's Viper Venom Time (dRVVT):

  • First-line test due to highest specificity for detecting LA in patients at high risk of thrombosis 1, 3
  • Most robust test according to international quality assessment programs 1
  • Not affected by factor VIII or IX inhibitors 4

• Activated Partial Thromboplastin Time (aPTT):

  • Second test of choice when performed with:
    • Silica as activator (NOT kaolin or ellagic acid)
    • Low phospholipid content (e.g., PTT-LA) 1, 3

Testing Protocol (3-Step Process)

1. Screening Phase:

   • Perform dRVVT and sensitive aPTT with low phospholipid content
   • Results are potentially suggestive of LA when clotting times exceed local cut-off value 1

2. Mixing Studies:

   • Mix patient plasma with pooled normal plasma (1:1 proportion)
   • Testing should be performed without pre-incubation within 30 minutes
   • Suggestive of LA when clotting times remain prolonged or when Index of Circulating Anticoagulant (ICA) exceeds cut-off 1

3. Confirmatory Testing:

   • Perform tests with high phospholipid concentration
   • Calculate percent correction: [(screen - confirm)/screen] × 100
   • Confirms LA if percent correction exceeds local cut-off value 1, 3

Important Technical Considerations

Sample Preparation

• Proper preparation of platelet-poor plasma is essential:
  • Double centrifugation to ensure minimal platelet contamination (<10^7/mL)
  • Store frozen at -70°C in small aliquots 1, 2

Potential Interferences

• Anticoagulants:

  • Heparin can interfere with results (some reagents contain neutralizers for up to 0.8 U/mL)
  • Low molecular weight heparin may affect results depending on FXa:FIIa ratio
  • Direct thrombin or FXa inhibitors may interfere 1, 3
  • Prior use of vitamin K antagonists or NOACs must be evaluated 4

• Medications:

  • Hydroxychloroquine may weakly interfere by affecting IgG-β2GPI complexes
  • Aspirin and clopidogrel do not interfere 1
  • Various drugs can induce LA formation 5

Clinical Applications

When to Test for LA

• Young patients (<50 years) with unprovoked venous or arterial thrombosis
• Thrombosis at unusual sites
• Women with recurrent pregnancy loss or late pregnancy complications
• Patients with unexplained prolonged aPTT
• Patients with autoimmune diseases, particularly SLE 3

Test Limitations

• No single assay detects every LA due to antibody heterogeneity 6
• False positives can occur with indiscriminate testing 3
• Testing should be repeated after >12 weeks to confirm persistence 3

Alternative Testing Methods

When standard tests are unreliable due to interferences:

• Taipan snake venom time
• Textarin time
• Dilute prothrombin time 6

Not recommended by guidelines due to standardization issues:

• Kaolin Clotting Time (KCT) - poor reproducibility
• Dilute prothrombin time (dPT) - variability in reagents
• Ecarin and Textarin assays - lack of standardized commercial assays 1

Remember that proper LA testing requires local establishment of cut-off values using at least 40 healthy donors under age 50, and results should always be reported with interpretative comments to guide clinical decision-making. 1