Haemophilia is an inherited bleeding disorder caused by deficiencies of clotting factors, leading to impaired haemostasis. It is crucial for UKMLA as a key cause of coagulopathy.

Types:

1. Haemophilia A:
   • Deficiency of factor VIII.
   • Most common form (~80% of cases).
2. Haemophilia B (Christmas disease):
   • Deficiency of factor IX.

Aetiology:

1. Genetics:
   • X-linked recessive inheritance (primarily affects males).
   • Female carriers may have mild symptoms.
2. Acquired Haemophilia:
   • Autoantibodies against clotting factors, typically in older adults or associated with autoimmune disease, malignancy, or postpartum state.

Pathophysiology:

• Insufficient clotting factor disrupts the intrinsic pathway of the coagulation cascade, leading to defective thrombin generation and impaired fibrin clot formation.

Clinical Features:

1. Bleeding Episodes:
   • Spontaneous or post-traumatic bleeding.
   • Common sites:
     • Joints (haemarthrosis): Pain, swelling, and limited movement.
     • Muscles: Haematomas causing swelling and pain.
     • Mucosal bleeding: Epistaxis, gastrointestinal, or genitourinary bleeding.
2. Complications:
   • Chronic arthropathy due to recurrent haemarthrosis.
   • Intracranial haemorrhage (rare but life-threatening).

Investigations:

1. Coagulation Studies:
   • Prothrombin Time (PT): Normal.
   • Activated Partial Thromboplastin Time (aPTT): Prolonged.
2. Clotting Factor Assays:
   • Reduced factor VIII in haemophilia A.
   • Reduced factor IX in haemophilia B.
3. Genetic Testing:
   • Identifies mutations in F8 (haemophilia A) or F9 (haemophilia B) genes.
4. Inhibitor Testing:
   • Detects antibodies against clotting factors in acquired haemophilia.

Classification:

Based on clotting factor activity levels:

1. Severe:
   • Factor activity <1% of normal.
   • Spontaneous bleeding.
2. Moderate:
   • Factor activity 1–5% of normal.
   • Bleeding with minor trauma.
3. Mild:
   • Factor activity 6–40% of normal.
   • Bleeding with significant trauma or surgery.

Management:

1. Factor Replacement Therapy:
   • Haemophilia A: Recombinant factor VIII.
   • Haemophilia B: Recombinant factor IX.
   • Frequency:
     • Prophylaxis: Regular infusions to prevent bleeding (especially in severe cases).
     • On-Demand: During acute bleeding episodes.
2. Bypassing Agents:
   • For patients with inhibitors (antibodies against replacement factors):
     • Activated Prothrombin Complex Concentrates (aPCC).
     • Recombinant Activated Factor VII (rFVIIa).
3. Novel Therapies:
   • Emicizumab: A bispecific antibody mimicking factor VIII activity (used in haemophilia A).
4. Supportive Measures:
   • RICE (Rest, Ice, Compression, Elevation) for joint bleeding.
   • Analgesia (avoid NSAIDs as they worsen bleeding risk).

Complications:

1. Inhibitor Formation:
   • Development of antibodies to replacement factors, reducing efficacy.
2. Chronic Arthropathy:
   • Due to recurrent haemarthrosis.
3. Psychosocial Impact:
   • Fear of bleeding episodes, reduced quality of life.
4. Infections (historical):
   • Transmission of HIV or hepatitis from contaminated blood products (now rare with modern treatments).

Prognosis:

• Excellent with early diagnosis and appropriate management.
• Severe forms may lead to significant joint damage and disability if untreated.

Key Exam Points for UKMLA:

1. Genetics:
   • X-linked inheritance; female carriers are usually asymptomatic.
2. Diagnosis:
   • Prolonged aPTT with normal PT; confirm with factor assays.
3. Management:
   • Regular factor replacement or novel therapies like emicizumab.
4. Complications:
   • Know the risks of inhibitor formation and chronic joint damage.
5. Differentials:
   • Von Willebrand disease (consider if both aPTT and bleeding time are prolonged).