Which hemostasis screening test(s) will be abnormal in patients with hemophilia A or B, specifically the Activated Partial Thromboplastin Time (APTT) and Prothrombin Time (PT)?

Abnormal Hemostasis Screening Tests in Hemophilia A and B

In patients with hemophilia A or B, the activated partial thromboplastin time (APTT) is the only hemostasis screening test that will be abnormal (Answer: A - APTT only).

Pathophysiology and Laboratory Findings in Hemophilia

Hemophilia A and B are X-linked recessive bleeding disorders characterized by deficiencies in coagulation factors:

• Hemophilia A: Factor VIII deficiency
• Hemophilia B: Factor IX deficiency

Both factors VIII and IX are part of the intrinsic coagulation pathway, which is specifically assessed by the APTT test 1. The prothrombin time (PT) remains normal because it evaluates the extrinsic pathway, which does not depend on factors VIII or IX 2.

Laboratory Test Patterns in Hemophilia:

• APTT: Prolonged in both hemophilia A and B

  • Severity correlates with degree of prolongation:
    • Severe (<1% factor activity): Markedly prolonged APTT
    • Moderate (1-5% factor activity): Moderately prolonged APTT
    • Mild (>5% to <40% factor activity): Mildly prolonged or occasionally normal APTT 1

• PT: Normal in both hemophilia A and B 2, 1

• Platelet count: Normal in both hemophilia A and B 3

Diagnostic Approach to Hemophilia

The typical diagnostic pathway for hemophilia includes:

1. Initial screening with APTT:

   • Prolonged APTT suggests factor deficiency or inhibitor 1
   • Normal PT helps differentiate from other coagulation disorders 3

2. Mixing studies:

   • Mixing patient plasma with normal pooled plasma
   • Complete correction indicates factor deficiency
   • Incomplete correction suggests inhibitor presence 3

3. Specific factor assays:

   • Measurement of FVIII, FIX levels for definitive diagnosis 1
   • One-stage APTT-based clotting assay is most commonly used worldwide 4
   • Chromogenic substrate assays are available in specialized laboratories 4

Important Clinical Considerations

Potential Pitfalls in Diagnosis:

• Mild hemophilia may have normal APTT:

  • Some patients with mild hemophilia B (FIX activity 27-34%) can present with normal APTT 5
  • Clinical history and specific factor assays are crucial even with normal screening tests

• Reagent sensitivity matters:

  • Different APTT reagents have varying sensitivities to factor deficiencies 2
  • The Journal of Thrombosis and Haemostasis notes that APTT reagent selection impacts detection of low factor levels 2

• Inhibitor development:

  • Factor VIII/IX inhibitors can develop in patients with hemophilia
  • These inhibitors will also prolong APTT but not PT 1
  • Bethesda assay is used to quantify inhibitor levels 1

Advanced Diagnostic Methods:

• Clot Waveform Analysis (CWA):

  • Enhanced APTT-based technique that provides additional information
  • Can detect very low levels of FVIII/FIX activity that conventional assays might miss 2
  • Particularly useful in severe hemophilia to differentiate between patients with <1% factor activity 2

• Thrombin Generation Assay:

  • Can detect hypocoagulability from factor VIII or IX deficiency
  • Useful for monitoring hemostatic therapies 2

Summary

In hemophilia A and B, the APTT is typically prolonged while PT and platelet count remain normal. This pattern reflects the specific deficiency in the intrinsic coagulation pathway (factors VIII or IX) while the extrinsic pathway remains intact. While rare cases of mild hemophilia may present with normal APTT, specific factor assays remain the gold standard for diagnosis.