What does a prolonged activated partial thromboplastin time (aPTT) result of 120.3 seconds after a 1:1 mix with normal plasma indicate in a patient with normal thrombin time and no bleeding symptoms?

Interpretation of Prolonged aPTT After Mixing Study

The prolonged aPTT of 120.3 seconds after a 1:1 mix with normal plasma indicates the presence of an inhibitor, not a factor deficiency (option C is correct).

Understanding the Laboratory Results

The patient's laboratory findings show:

• Normal platelet count (256 x 10³/μL)
• Normal prothrombin time (11.6 sec)
• Severely prolonged aPTT (125.9 sec)
• After 1:1 mix with normal plasma, aPTT remains prolonged (120.3 sec)
• Normal thrombin time

Analysis of Mixing Study Results

When interpreting mixing studies, we need to understand the principle behind them 1:

• In factor deficiencies, mixing with normal plasma (which contains all factors) should correct the prolonged aPTT
• In the presence of inhibitors, mixing with normal plasma will not correct the prolongation
• The minimal correction seen in this case (from 125.9 to 120.3 seconds) indicates the presence of an inhibitor

Differential Diagnosis of the Inhibitor

The most likely inhibitors in this clinical scenario include:

1. Lupus anticoagulant - most probable given:

   • Marked prolongation of aPTT
   • No correction with mixing study
   • Normal thrombin time (rules out heparin contamination)
   • No bleeding symptoms (lupus anticoagulants paradoxically increase thrombosis risk)

2. Factor VIII inhibitor - less likely because:

   • Patient has no bleeding symptoms (FVIII inhibitors typically cause bleeding)
   • The degree of prolongation is very severe 2

Why Other Options Are Incorrect

• Option A (The original APTT test was corrected): Clearly incorrect as the aPTT remained severely prolonged after mixing (120.3 sec vs. reference range 23-36 sec) 3

• Option B (There is a factor deficiency): Factor deficiencies typically correct with mixing studies as normal plasma provides the missing factors 3

• Option D (The specimen is contaminated with heparin): Ruled out by the normal thrombin time, as thrombin time is extremely sensitive to heparin 3, 4

Clinical Implications

This pattern strongly suggests a lupus anticoagulant, which:

• Is a time-dependent inhibitor that interferes with phospholipid-dependent coagulation tests
• Typically causes prolonged aPTT that doesn't correct with mixing
• Usually doesn't cause bleeding (may actually increase thrombosis risk)
• Has normal thrombin time (unlike heparin contamination) 5, 6

Next Steps in Management

1. Confirm lupus anticoagulant with specific testing:

   • Dilute Russell Viper Venom Time (dRVVT)
   • Hexagonal phase phospholipid neutralization
   • Platelet neutralization procedure

2. If confirmed, evaluate for associated conditions:

   • Antiphospholipid syndrome
   • Autoimmune disorders (SLE)
   • Malignancy
   • Infections

3. Assess thrombotic risk and consider anticoagulation if indicated

Pitfalls to Avoid

• Don't assume prolonged aPTT means bleeding risk; lupus anticoagulants are associated with thrombosis
• Don't mistake non-correction in mixing study for heparin contamination when thrombin time is normal
• Don't confuse factor inhibitors (which cause bleeding) with lupus anticoagulants (which cause thrombosis)
• Don't rely solely on aPTT for monitoring if anticoagulation is needed; consider alternative tests like anti-Xa assays 3