What labs should be ordered for a patient with an elevated Partial Thromboplastin Time (PTT)?

Diagnostic Workup for Elevated PTT

For a patient with an elevated Partial Thromboplastin Time (PTT), a systematic laboratory evaluation should include mixing studies, specific factor assays, and lupus anticoagulant testing to determine the underlying cause. 1

Initial Diagnostic Steps

1. Mixing Studies:

   • Perform immediately and after 2-hour incubation at 37°C
   • Mix patient plasma with normal pooled plasma in 1:1 ratio
   • Assess correction pattern:
     • Immediate correction that persists: Factor deficiency likely
     • Immediate correction with prolongation after incubation: Time-dependent inhibitor (e.g., FVIII inhibitor)
     • No correction: Immediate-acting inhibitor (e.g., lupus anticoagulant)

2. Complete Blood Count (CBC) and Platelet Count:

   • Rule out thrombocytopenia which may coexist with coagulation disorders 1

Specific Factor Assays

If mixing studies suggest factor deficiency or results are equivocal:

• Measure intrinsic pathway factors:

  • Factor VIII, IX, XI, and XII levels 1
  • An isolated low FVIII level suggests acquired hemophilia A
  • Multiple low factor levels may represent either multiple deficiencies or an in vitro artifact

• Consider prekallikrein and high-molecular-weight kininogen if other factor levels are normal 2

Lupus Anticoagulant Testing

If mixing studies suggest an inhibitor:

• Perform specific lupus anticoagulant tests:

  • Dilute Russell's Viper Venom Time (dRVVT) - most robust test for LA detection 1
  • Silica-based aPTT with low phospholipid content 1
  • Confirmatory test with increased phospholipid concentration

• Interpretation:

  • LA is present if percentage correction with high phospholipid concentration exceeds the established cut-off 1

Additional Testing Based on Clinical Context

• Thrombin Time (TT):

  • To detect heparin or direct thrombin inhibitors
  • Prolonged TT with normal reptilase time suggests heparin effect 1

• Factor assays at higher dilutions:

  • If lupus anticoagulant is suspected to cause artifactual lowering of factor levels 1

• Bethesda Assay:

  • For quantification of factor inhibitors, particularly FVIII inhibitors
  • Report the titer corresponding to the dilution closest to 50% inhibition 1

• FVIII antibody ELISA:

  • Useful in complex cases to distinguish between lupus anticoagulant and acquired FVIII inhibitor 1

Common Pitfalls and Caveats

1. Pre-analytical variables affecting results:

   • Recent heparin administration (check thrombin time)
   • Improper sample collection or processing
   • Lipemic samples can interfere with optical detection methods

2. Interpretation challenges:

   • Immediate correction of PTT with normal plasma does not exclude acquired hemophilia A 1
   • Lupus anticoagulant can cause artifactual lowering of factor levels 1
   • Factor inhibitors may not be initially apparent and may require re-screening after several days 1

3. Age-specific considerations:

   • Reference ranges for coagulation tests are age-dependent and reagent-specific 1
   • Using adult reference ranges for pediatric patients may lead to misdiagnosis

4. Technical considerations:

   • Different aPTT reagents have varying sensitivities to factor deficiencies and lupus anticoagulant 3
   • Ensure proper sample processing: double centrifugation for lupus anticoagulant testing 1

By following this systematic approach to elevated PTT evaluation, clinicians can efficiently identify the underlying cause and implement appropriate management strategies to reduce morbidity and mortality associated with coagulation disorders.