Acquired Haemophilia A: Are We Missing the Diagnosis?

‍by Dr. Pamela Moodley – Haematologist

PATHCHAT Edition No. 14
Please contact your local Ampath pathologist for more information.

Introduction

🔹 What is Acquired Haemophilia A?

• A rare bleeding disorder caused by an autoantibody to Factor VIII.
• Often mistaken for other acquired bleeding disorders such as disseminated intravascular coagulation (DIC).
• Delayed or incorrect diagnosis can lead to severe bleeding and poor outcomes.
• There is no clear correlation between Factor VIII levels, inhibitor strength, and severity of bleeding.
• Patients remain at risk of life-threatening bleeding until the inhibitor is eradicated.

Comparison Between Classical & Acquired Haemophilia A

🔹 Classical Haemophilia A (Congenital)

• Genetic (sex-linked inheritance).
• Factor VIII deficiency due to reduced production.
• Predominantly affects males, while females are carriers.
• Presents in childhood.
• Bleeding occurs in joints (haemarthrosis) and muscles.

🔹 Acquired Haemophilia A

• Autoimmune disorder (not inherited).
• Factor VIII deficiency due to autoantibodies against Factor VIII.
• Affects both males and females.
• Presents in adulthood.
• Bleeding occurs in skin and soft tissues.

Clinical Presentation

🔹 Common Symptoms of Acquired Haemophilia A:

• Unusual or uncontrolled bleeding.
• Extensive bruising (ecchymoses).
• Soft tissue haemorrhage.
• Prolonged bleeding post-surgery or postpartum.
• Compartment syndrome due to internal bleeding.

Conditions Associated With Acquired Haemophilia A

• Autoimmune diseases (e.g., systemic lupus erythematosus (SLE), rheumatoid arthritis).
• Collagen vascular disorders.
• Asthma.
• Skin diseases.
• Malignancies.
• Pregnancy-related complications.
• Drug-induced immune reactions.

Laboratory Testing for Diagnosis

🔹 Key Findings in Acquired Haemophilia A:

• Unexplained prolonged activated partial thromboplastin time (aPTT).
• Normal prothrombin time (PT).
• Normal platelet count and function.
• Low Factor VIII levels.
• Mixing study confirms the presence of a time-dependent inhibitor.

🔹 Expected Laboratory Findings:

TestNormal RangeAcquired Haemophilia AaPTT25–40 secIncreasedPT9.0–13 secNormalThrombin Time14.0–21 secNormalFibrinogen2.00–4.00 g/dLNormalFactor VIII Activity50–150%DecreasedAnti-FVIII AntibodyNot presentPresent

📌 Normal ranges are site-specific (Ampath reference ranges). Confounding drugs or illnesses may alter results.

Diagnostic Approach: Step-by-Step Guide

🔹 Step 1: Identify a Prolonged aPTT in a Bleeding Patient

• No personal or family history of bleeding disorder.

🔹 Step 2: Perform a Mixing Study

• Mix patient plasma with normal plasma (1:1 ratio) and measure aPTT at 0 and 2 hours.

Interpreting Results:
✅ aPTT correction → Suggests a Factor Deficiency

• Measure Factors VIII, IX, XI, and XII to confirm the specific deficiency.

🚨 Weak or No aPTT Correction → Suggests an Inhibitor

• Possible Acquired Haemophilia A or Lupus Anticoagulant.
• Confirm Factor VIII deficiency and perform Bethesda assay for inhibitor quantification.

Treatment of Acquired Haemophilia A

🔹 Two-Step Approach: Stop Bleeding & Eradicate Inhibitors

1. Stopping Bleeding (First-Line Therapy)

✅ Bypassing Agents (Preferred):

• Recombinant activated Factor VII (rFVIIa) – NovoSeven.
• Activated prothrombin complex concentrates (FEIBA).

✅ Alternative Therapy (If Bypassing Agents Are Unavailable):

• Human or recombinant Factor VIII concentrates (less effective due to inhibitor presence).
• Desmopressin (DDAVP) in mild cases.

2. Inhibitor Eradication (Long-Term Therapy)

✅ First-Line:

• Immunosuppressive therapy (Prednisone alone or with Cyclophosphamide).

✅ Second-Line (For Resistant Cases):

• Immunomodulatory therapy to prevent antibody production.
• Plasmapheresis (removes circulating inhibitors from blood) in severe cases.

Follow-Up & Monitoring

🔹 Relapse Risk:

• Bleeding may recur if immunosuppressive therapy is tapered too quickly.

🔹 Recommended Monitoring:

• Follow up for at least 1 year after treatment.
• Monitor aPTT levels regularly to assess inhibitor eradication.

Key Takeaways for Clinicians

✅ Always consider Acquired Haemophilia A in patients with an isolated prolonged aPTT and unexplained bleeding.
✅ Factor VIII levels and Bethesda titres do NOT predict bleeding severity.
✅ Fatal bleeding can occur until the inhibitor is eradicated.
✅ Consult a haematologist early for accurate diagnosis and management.
✅ Early and aggressive treatment improves outcomes.

References

1. Giangrande, P. (2012). Acquired Haemophilia. Treatment of Haemophilia (No. 38).
2. Collins, P. et al. (2010). Consensus Recommendations for the Diagnosis and Treatment of Acquired Haemophilia A. BMC Research Notes.
3. Huth-Kühne, A. et al. (2009). International Recommendations on the Diagnosis and Treatment of Patients with Acquired Haemophilia A. Haematologica.