What is the target International Normalized Ratio (INR) range in patients with erratic INR values due to lupus anticoagulant?

Target INR Range for Patients with Lupus Anticoagulant

For patients with erratic INR values due to lupus anticoagulant, the standard INR target range of 2.0-3.0 should be maintained, but monitoring should be done using LA-insensitive thromboplastins with proper instrument-specific ISI calibration. 1, 2

Understanding the Problem

Lupus anticoagulant (LA) can interfere with INR measurements in some patients, leading to:

• Falsely elevated INR readings
• Inconsistent results between different laboratory methods
• Challenges in appropriate warfarin dosing

The interference occurs because:

• LA binds to phospholipids in the test system
• Different commercial thromboplastins have varying sensitivity to LA
• This can result in between-thromboplastin variability that is higher in LA-positive patients (CV=12.4%) compared to controls (CV=6.7%) 1

Recommended Approach

1. Verify Thromboplastin Sensitivity

• Check baseline PT before starting warfarin therapy
• A prolonged baseline PT suggests the local thromboplastin is sensitive to the patient's LA 2

2. Select Appropriate Testing Method

• Use LA-insensitive thromboplastins with proper instrument-specific ISI calibration 1, 2
• Avoid recombinant relipidated tissue factor-based thromboplastins unless specifically tested for LA sensitivity 1
• Avoid point-of-care INR devices as they may be variably affected by LA 1, 2

3. Alternative Monitoring Methods

If INR values remain erratic despite using LA-insensitive thromboplastins:

• Consider chromogenic factor X assay for monitoring instead of INR 3, 4
  • Therapeutic range for factor X activity is 22-40% of normal 4
  • This assay is not affected by LA but may be more expensive and less widely available 5

4. Maintain Standard Target INR Range

• For venous thromboembolism: INR 2.0-3.0 6
• For patients with antiphospholipid antibodies: INR 2.0-3.0 6

Important Caveats

• In a study of LA-positive patients with therapeutic factor X levels (22-40%), 39% had INR values above 3.0, and 11% had values above 4.0, suggesting potential overestimation of anticoagulation 4
• Factor X and factor II activity levels don't always agree in warfarin-treated LA patients, with some patients showing strong disagreement (FII/CFX ratio <0.6) 3
• The phospholipid-rich dilute Russell's viper venom time (prdRVVT) is not suitable for monitoring warfarin therapy in patients with LA 5
• Patients with anticardiolipin antibodies but without LA don't appear to have significant INR interference 7

Clinical Decision Algorithm

1. Initial Assessment:

   • Determine if baseline PT is prolonged before starting warfarin
   • Identify which thromboplastin reagent is used by your laboratory

2. Monitoring Strategy:

   • If using LA-insensitive thromboplastin: maintain standard INR target of 2.0-3.0
   • If INR values are erratic or suspiciously high: request chromogenic factor X assay
   • If factor X is 22-40% of normal: patient is adequately anticoagulated regardless of INR

3. Laboratory Communication:

   • Inform the laboratory about the patient's LA status
   • Request consistent use of the same thromboplastin reagent for all testing

By following these guidelines, you can maintain appropriate anticoagulation while minimizing the risk of both thrombotic events and bleeding complications in patients with lupus anticoagulant.