In patients with lupus (Systemic Lupus Erythematosus) and a positive coagulation test, what is the variation in International Normalized Ratio (INR) values?

INR Variation in Lupus Patients with Positive Coagulation Tests

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

Understanding INR Variability in Lupus Anticoagulant Patients

Magnitude of Variation

• The International Society on Thrombosis and Haemostasis reports that the between-thromboplastin variability of PT-INR in LA-positive patients has a coefficient of variation (CV) of 12.4%, compared to 6.7% in controls without LA 2
• This variability means that INR readings can differ significantly depending on which laboratory reagent (thromboplastin) is used for testing
• In some cases, patients may have falsely elevated INR values that significantly overestimate their true anticoagulation status 1

Factors Affecting INR Variability

• Thromboplastin type: Different commercial thromboplastins have varying sensitivities to LA interference 2

  • Recombinant thromboplastins (particularly human recombinant types) tend to be more sensitive to LA interference 2, 3
  • One specific thromboplastin (Thromborel R) showed considerably greater INR values in LA-positive patients but has been discontinued 2

• Test dilution factor: Combined thromboplastins with higher final test plasma dilution (1:20) show less interference than recombinant thromboplastins with lower dilution (1:3) 3

• Anticoagulation intensity: Variation increases at supratherapeutic levels of anticoagulation 4

• Stability of anticoagulation: Greater variation is observed in patients who have just started warfarin or have not achieved stable anticoagulation 4

Clinical Implications and Management

Monitoring Recommendations

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

2. Avoid point-of-care (POC) INR devices in LA-positive patients, as results from these devices may be inconsistent and unreliable 2, 1

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

   • Chromogenic factor X assay (therapeutic range: 22-40% of normal) 1, 5
   • In one study, 39% of LA-positive patients with therapeutic factor X levels (22-40%) had INR values above 3.0, and 11% had INR values above 4.0, indicating significant overestimation 5

4. Check baseline PT/INR before starting warfarin therapy to verify if the local thromboplastin is sensitive to the patient's LA 1

Important Caveats

• Factor X and factor II activity levels do not always agree in warfarin-treated LA patients, with some patients showing strong disagreement (FII/CFX ratios less than 0.6) 6

• The phospholipid-rich dilute Russell's viper venom time (prdRVVT) is not suitable for monitoring warfarin therapy in patients with LA 7

• Anti-cardiolipin IgG titer and anti-β2GPI IgG titer are positively associated with the degree of INR overestimation in LA patients 3

Practical Approach to Managing INR Variability

1. Establish baseline: Determine if the patient's LA affects INR measurements before starting warfarin

2. Use consistent laboratory method: Always use the same thromboplastin reagent and laboratory for monitoring

3. Monitor for discrepancies: Be alert for clinical signs of under- or over-anticoagulation that don't match INR values

4. Consider chromogenic factor X testing: When INR values seem discordant with clinical status or when values are erratic despite stable dosing

5. Avoid frequent dose adjustments: Based solely on single INR values that seem inconsistent with the clinical picture or previous stable pattern

This approach helps minimize the risk of inappropriate warfarin dosage adjustments that could lead to thrombotic events (if dose is inappropriately reduced) or bleeding complications (if INR is underestimated).