How much can INR vary in a patient with lupus anticoagulant due to false readings?

INR Variability in Patients with Lupus Anticoagulant

In patients with lupus anticoagulant, INR readings can show a variability of approximately 12.4% (coefficient of variation) between different thromboplastin reagents, compared to 6.7% in patients without lupus anticoagulant, with some patients showing falsely elevated INR values that can be more than 1.0 point higher than their true anticoagulation status. 1, 2

Understanding the Interference of Lupus Anticoagulant on INR

Lupus anticoagulant (LA) can interfere with INR measurements through the following mechanisms:

• LA binds to phospholipids in the test system, potentially causing falsely elevated INR readings
• The degree of interference varies based on:
  • The specific thromboplastin reagent used in testing
  • The phospholipid composition and concentration in the reagent
  • Individual patient characteristics

Extent of INR Variation

• Between-thromboplastin variability (CV) in LA-positive patients: 12.4% 1
• Between-thromboplastin variability (CV) in LA-negative patients: 6.7% 1
• Approximately 39% of LA-positive patients with therapeutic anticoagulation (based on factor X levels) may show INR values above 3.0 3
• About 11% of LA-positive patients may have INR values falsely elevated above 4.0 3
• The interference occurs in approximately 6.5% of patients with LA 4

Clinical Implications and Management

Identifying False INR Readings

Signs that suggest INR readings may be falsely elevated:

• Discordance between INR values and clinical presentation (no bleeding despite high INR)
• Erratic INR values despite stable warfarin dosing
• Significant differences in INR values when measured with different laboratory methods
• Prolonged baseline PT before starting warfarin therapy

Monitoring Recommendations

1. Use LA-insensitive thromboplastins with proper instrument-specific ISI calibration 1, 2

2. Avoid thromboplastins known to be sensitive to LA, particularly those based on recombinant relipidated tissue factor 2

3. Consider alternative monitoring methods when INR results are suspected to be unreliable:

   • Chromogenic factor X assay (therapeutic range: 22-40% of normal activity) 2, 3
   • This assay is phospholipid-independent and therefore not affected by LA

4. Avoid point-of-care INR devices as they may be variably affected by LA 2

5. Do not use phospholipid-rich dilute Russell's viper venom time (prdRVVT) for monitoring warfarin therapy in LA patients, as studies show poor correlation with actual anticoagulation status 5

Important Caveats

• Factor II and Factor X activity levels may not always agree in warfarin-treated LA patients, with some patients showing strong disagreement (FII/CFX ratio <0.6) 6

• The variation in INR increases at supratherapeutic levels of anticoagulation and when anticoagulation is unstable 7

• Checking baseline PT before starting warfarin therapy can help identify if the local thromboplastin is sensitive to the patient's lupus anticoagulant 2

• Failure to recognize falsely elevated INR readings may lead to inappropriate warfarin dose reductions and inadequate anticoagulation, potentially resulting in recurrent thrombosis 3, 4