Why does lupus anticoagulant increase activated partial thromboplastin time (aPTT) and not prothrombin time (PT)?

Why Lupus Anticoagulant Increases aPTT and Not PT

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, 2

Mechanism of LA Interference with Coagulation Tests

Phospholipid Concentration Differences

• aPTT reagents: Contain relatively lower phospholipid concentrations, making them susceptible to LA interference
• PT reagents: Contain much higher phospholipid concentrations that typically "quench" or neutralize the LA activity 2

How LA Works

• Lupus anticoagulants are immunoglobulins (IgG, IgM, and/or IgA) that interfere with phospholipid-dependent coagulation tests 3
• They bind to phospholipid-binding proteins (primarily β2-glycoprotein I or prothrombin) rather than directly to phospholipids
• This binding disrupts the assembly of coagulation complexes on phospholipid surfaces

Variability in Thromboplastin Sensitivity

While most PT tests are resistant to LA interference, there is notable variability among commercial thromboplastins:

• 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
• One study found that only 4.3% of 400 non-anticoagulated LA-positive patients had prolonged PT when using a recombinant thromboplastin (Innovin) 4

Clinical Implications

Monitoring Anticoagulation

• The between-thromboplastin variability of PT-INR in LA-positive patients (CV of 12.4%) is significantly higher than in LA-negative patients (CV of 6.7%) 2
• This variability can complicate monitoring of vitamin K antagonist therapy in LA-positive patients

Diagnostic Considerations

• A prolonged aPTT with normal PT in a patient with systemic lupus erythematosus typically suggests the presence of LA 5
• However, it's crucial to distinguish between LA and true factor inhibitors (like factor VIII inhibitors), as the latter can cause life-threatening bleeding 5

Rare Exceptions

In rare cases, LA can affect PT measurements:

• Some patients with LA may develop hypoprothrombinemia (low factor II levels), resulting in prolonged PT 6, 7
• This condition, known as hypoprothrombinemia-lupus anticoagulant syndrome (HLAS), can cause severe bleeding despite the paradoxical association of LA with thrombosis 6

Best Practices for Laboratory Testing

• Establish a baseline PT/INR measurement before starting warfarin therapy to verify if the local thromboplastin is sensitive to the patient's LA 2
• Use LA-insensitive thromboplastins with proper instrument-specific ISI calibration when monitoring LA patients on warfarin 2
• Consider chromogenic factor X assay as an alternative monitoring method when INR results are suspected to be unreliable 2
• Avoid point-of-care INR devices in LA-positive patients, as results may be inconsistent 2

Understanding this differential effect on coagulation tests is essential for proper diagnosis and management of patients with LA, especially when anticoagulation therapy is required.