Coagulation Disorders

Introduction to Lupus Anticoagulant

• Lupus anticoagulant (LA) typically increases activated partial thromboplastin time (aPTT) but not prothrombin time (PT) because PT reagents contain much higher phospholipid concentrations than aPTT reagents, which effectively neutralizes the LA interference 1
• Lupus anticoagulant (LA) positive patients show significantly higher between-thromboplastin variability in INR measurements compared to LA-negative patients, supporting the need for alternative monitoring methods when INR results are unreliable, as confirmed by the International Society on Thrombosis and Haemostasis 1

Mechanism of Lupus Anticoagulant Interference

• Different commercial thromboplastins have varying sensitivities to LA interference, with recombinant thromboplastins (particularly human recombinant types) tend to be more sensitive to LA interference 1
• Phospholipid composition and concentrations vary among commercial thromboplastins, making this effect inconsistent across different laboratory systems 1

Diagnosis and Monitoring of Lupus Anticoagulant

• 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, as shown in the following table:

1

• The baseline PT in patients with LA is rarely prolonged because phospholipid concentrations in PT reagents are much higher than those in APTT, which typically quenches LA activity 1

Management of Patients with Lupus Anticoagulant

• The chromogenic factor X assay is recommended as an alternative monitoring method when INR results are suspected to be unreliable, as it is not sensitive to lupus anticoagulant interference, with a therapeutic range for factor X activity of 22-40% of normal 1, 2
• LA-insensitive thromboplastins with proper instrument-specific ISI calibration should be used when monitoring LA patients on warfarin, as recommended by the International Society on Thrombosis and Haemostasis 1
• Point-of-care INR devices should be avoided in LA-positive patients, as results from these devices may be inconsistent and unreliable 1, 2
• A baseline INR measurement should be established before starting warfarin therapy to verify if the local thromboplastin is sensitive to the patient's LA, and checking baseline PT before starting warfarin therapy can help verify this sensitivity, as recommended by the Journal of Thrombosis and Haemostasis and Praxis Medical Insights 1, 2
• Direct oral anticoagulants (DOACs) may be considered as an alternative treatment option for LA patients with unreliable INR measurements, as suggested by Praxis Medical Insights 1, 2
• Factors that can influence INR measurement accuracy include citrate concentration in blood collection tubes, underfilled collection tubes, and automated clot detectors, as reported by the American College of Cardiology 3
• Using a consistent laboratory method, monitoring for discrepancies between INR values and clinical signs, and considering chromogenic factor X testing can help minimize the risk of inappropriate warfarin dosage adjustments, and avoiding frequent dose adjustments based solely on single INR values that seem inconsistent with the clinical picture or previous stable pattern is recommended 1
• If INR values remain erratic despite using LA-insensitive thromboplastins, alternative monitoring methods, such as chromogenic factor X assay, or discussing alternative anticoagulation options, such as direct oral anticoagulants (DOACs), may be necessary, as suggested by Praxis Medical Insights 1, 2