Haemophilia A

Related Subjects: |Haemophilia A |Haemophilia B |Haemolytic anaemia

A classic X-linked bleeding disorder, six times more common than Haemophilia B.

📖 About

• Haemophilia A: X-linked genetic disorder due to defective clotting factor VIII, almost exclusively affecting males 👨.
• ~30% of cases arise from new mutations 🧬.
• History: Queen Victoria was a carrier and passed the gene into European royalty 👑.
• 1980s: many patients acquired HIV and hepatitis C from contaminated blood products 💉.

🧬 Aetiology

• Inherited deficiency of factor VIII:C due to mutations on the X chromosome.
• >200 mutations identified; ~50% due to inversion of intron 22.

📊 Background

• Prevalence: ~1 in 5,000 males 👦.
• Males affected; females carriers (except in Turner syndrome XO).
• Carriers may have reduced factor VIII due to lyonisation (X-inactivation) ♀️.
• Haemophilia A is ~6× more common than Haemophilia B.

📉 Grading by Factor VIII Levels

• Severe: <2% → spontaneous haemarthrosis 🤕, muscle haematomas.
• Moderate: 2–10% → bleeding after minor trauma/surgery 🩸.
• Mild: 10–50% → excessive bleeding only after major surgery/trauma 🏥.

⚡ Clinical Features

• Bleeding rarely evident in newborn period; problems arise with mobility 🍼➡️🚶.
• Bleeding after procedures (e.g., circumcision ✂️).
• Haematomas appear after ~6 months of age.
• Recurrent haemarthroses → chronic arthritis and joint deformity 🦵.
• Risk of intracranial haemorrhage, especially post-head injury 🧠.
• Minor cuts/abrasions not a problem (platelets normal ✅).

🔬 Investigations

• APTT: prolonged ⏱️.
• Factor VIII:C: reduced 📉.
• VWF: normal ✅ (helps distinguish from von Willebrand disease).
• PT, bleeding time, platelet count: normal 📊.
• Female carriers: factor VIII ~50% of normal.

👶 Prenatal Diagnosis

• Possible via chorionic villous sampling at ~11 weeks if mutation known 🧬.

🩺 Management

• Avoid aspirin, NSAIDs, intramuscular injections, and high-risk trauma activities 🚫.
• Mild disease: Desmopressin (IV/SC/intranasal) → slight ↑ in Factor VIII 💉.
• IV Factor VIII replacement = mainstay of therapy, can restore near-normal life expectancy 🌱.
• Home therapy: factor VIII concentrate for urgent use 🏠.
• Half-life of factor VIII ~12 hours ⏳ → dosing usually twice daily (bd).
• Severe disease: prophylactic infusions 3× weekly prevent spontaneous bleeds.

💉 Replacement Therapy Targets

• Joint bleed → raise FVIII to 30–40% 🦵.
• Life-threatening bleed → raise FVIII to 80–100% ⚠️.
• Prophylaxis prevents spontaneous bleeds.
• FVIII sourced from plasma or recombinant engineering 🧪.

⚠️ Complications

• Blood-borne infections (HIV, Hep B/C) from past contaminated blood products 🦠.
• Development of inhibitors (antibodies) to factor VIII → refractory bleeding; may require bypass therapy (Factor VIIa) 💉.

Cases — Haemophilia A

• Case 1 — Child with Spontaneous Joint Bleed: A 7-year-old boy is brought to A&E with a painful swollen right knee after minor trauma. He has recurrent episodes of joint swelling since age 2. FBC is normal, PT normal, but APTT prolonged. Factor VIII level <1%. Diagnosis: Severe Haemophilia A with haemarthrosis.
• Case 2 — Post-Surgical Bleeding: A 22-year-old man develops persistent bleeding 12 hours after a dental extraction. Past history includes prolonged bleeding after circumcision. Coagulation studies: PT normal, APTT prolonged, low Factor VIII activity (12%). Diagnosis: Moderate Haemophilia A, presenting with excessive surgical bleeding.
• Case 3 — Inhibitor Development: A 30-year-old man with known severe Haemophilia A is admitted with persistent thigh haematoma after intramuscular injection. He has had multiple prior Factor VIII infusions. Factor VIII levels do not correct as expected after treatment; Bethesda assay confirms inhibitors. Diagnosis: Haemophilia A with inhibitor antibodies.

Teaching Commentary 🩸

Haemophilia A is an X-linked recessive deficiency of Factor VIII, the most common inherited bleeding disorder after von Willebrand disease. Severity depends on Factor VIII activity: - <1% = severe (spontaneous joint/muscle bleeds), - 1–5% = moderate (bleeding after minor trauma), - >5% = mild (bleeding after surgery/dental work). Key labs: prolonged APTT, normal PT and platelets. Mainstay treatment is recombinant Factor VIII replacement or, in some mild cases, desmopressin (DDAVP). A major complication is development of inhibitor antibodies against Factor VIII, requiring bypassing agents (e.g., recombinant Factor VIIa, emicizumab). Long-term, recurrent haemarthroses can cause chronic arthropathy.