What does a prolonged prothrombin time (PT) and activated partial thromboplastin time (aPTT) indicate as a cause of spontaneous bruising?

Abnormal PT and aPTT Patterns in Spontaneous Bruising

A prolonged prothrombin time (PT) and activated partial thromboplastin time (aPTT) in a patient with spontaneous bruising most strongly indicates acquired hemophilia A (AHA), characterized by autoantibodies against factor VIII, which should be investigated with specific factor assays and mixing studies.1

Diagnostic Approach to Prolonged PT and aPTT

Initial Assessment

• Prolonged PT and aPTT together suggest either multiple factor deficiencies or inhibitors affecting both the intrinsic and extrinsic coagulation pathways 1
• Mixing studies should be performed to distinguish between factor deficiencies and inhibitors 1
• Time-dependent prolongation (worsening after 1-2 hour incubation) suggests the presence of an inhibitor rather than factor deficiency 1

Key Causes of Prolonged PT and aPTT with Spontaneous Bruising

1. Acquired Hemophilia A

   • Characterized by autoantibodies against factor VIII 1
   • Presents with spontaneous bruising and severe bleeding 1
   • Typically shows isolated low FVIII levels with prolonged aPTT 1
   • Mixing studies show incomplete correction that worsens after incubation 1

2. Lupus Anticoagulant-Hypoprothrombinemia Syndrome (LAHPS)

   • Rare disorder with lupus anticoagulant and acquired prothrombin deficiency 2
   • Can present with severe hemorrhagic manifestations 2
   • Associated with systemic lupus erythematosus or infections 2

3. Anticoagulant Medication Effects

   • Warfarin can prolong PT/INR primarily but may also affect aPTT 3
   • Heparin primarily affects aPTT but can influence PT/INR results 3
   • Warfarin may increase aPTT even in the absence of heparin 3

Diagnostic Testing Algorithm

Step 1: Mixing Studies

• Mix patient plasma with normal plasma in 1:1 ratio 1, 4
• Test immediately and after 1-2 hours of incubation at 37°C 1
• Interpretation:
  • Correction (normalization) suggests factor deficiency 4
  • Partial correction or no correction suggests inhibitor presence 4
  • Time-dependent worsening (prolongation after incubation) is typical of factor VIII autoantibodies 1

Step 2: Specific Factor Assays

• For prolonged aPTT: Measure factors VIII, IX, XI, and XII 1
• For prolonged PT: Measure factors II, V, VII, and X 4
• For both prolonged: Measure factors in both pathways plus common pathway 4
• An isolated low FVIII level is highly suggestive of acquired hemophilia A 1

Step 3: Inhibitor Testing

• Bethesda assay to quantify FVIII inhibitors 1
• Index of circulating anticoagulant (ICA) calculation (ICA >11% has high sensitivity for lupus anticoagulant) 4
• Specific lupus anticoagulant testing if suspected 1

Important Clinical Considerations

• Factor XII deficiency causes prolonged aPTT but is NOT associated with bleeding tendency 5
• Lupus anticoagulant typically prolongs aPTT but can paradoxically be associated with thrombosis rather than bleeding 1, 5
• In acquired hemophilia A, the inhibitor titer may not be initially apparent and re-screening may be necessary after several days 1
• Prolongation of PT and aPTT can occur in abusive head trauma due to parenchymal damage and should not automatically be interpreted as evidence of a primary bleeding disorder 1

Pitfalls to Avoid

• Do not assume that immediate correction of aPTT with normal plasma excludes acquired hemophilia A - further investigation is still required if clinical presentation is suggestive 1
• Lupus anticoagulant can cause artefactual lowering of factor levels due to inhibition of phospholipid in the assay 1
• Factor assays should be repeated at higher serial dilutions to attenuate the effect of inhibitors 1
• Inappropriate specimen handling commonly leads to false-positive coagulation test results 1
• Avoid unnecessary testing in asymptomatic individuals to prevent false-positive results 1