About Lesson
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:
- Haemophilia A:
- Deficiency of factor VIII.
- Most common form (~80% of cases).
- Haemophilia B (Christmas disease):
- Deficiency of factor IX.
Aetiology:
- Genetics:
- X-linked recessive inheritance (primarily affects males).
- Female carriers may have mild symptoms.
- 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:
- 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.
- Complications:
- Chronic arthropathy due to recurrent haemarthrosis.
- Intracranial haemorrhage (rare but life-threatening).
Investigations:
- Coagulation Studies:
- Prothrombin Time (PT): Normal.
- Activated Partial Thromboplastin Time (aPTT): Prolonged.
- Clotting Factor Assays:
- Reduced factor VIII in haemophilia A.
- Reduced factor IX in haemophilia B.
- Genetic Testing:
- Identifies mutations in F8 (haemophilia A) or F9 (haemophilia B) genes.
- Inhibitor Testing:
- Detects antibodies against clotting factors in acquired haemophilia.
Classification:
Based on clotting factor activity levels:
- Severe:
- Factor activity <1% of normal.
- Spontaneous bleeding.
- Moderate:
- Factor activity 1–5% of normal.
- Bleeding with minor trauma.
- Mild:
- Factor activity 6–40% of normal.
- Bleeding with significant trauma or surgery.
Management:
- 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.
- Bypassing Agents:
- For patients with inhibitors (antibodies against replacement factors):
- Activated Prothrombin Complex Concentrates (aPCC).
- Recombinant Activated Factor VII (rFVIIa).
- For patients with inhibitors (antibodies against replacement factors):
- Novel Therapies:
- Emicizumab: A bispecific antibody mimicking factor VIII activity (used in haemophilia A).
- Supportive Measures:
- RICE (Rest, Ice, Compression, Elevation) for joint bleeding.
- Analgesia (avoid NSAIDs as they worsen bleeding risk).
Complications:
- Inhibitor Formation:
- Development of antibodies to replacement factors, reducing efficacy.
- Chronic Arthropathy:
- Due to recurrent haemarthrosis.
- Psychosocial Impact:
- Fear of bleeding episodes, reduced quality of life.
- 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:
- Genetics:
- X-linked inheritance; female carriers are usually asymptomatic.
- Diagnosis:
- Prolonged aPTT with normal PT; confirm with factor assays.
- Management:
- Regular factor replacement or novel therapies like emicizumab.
- Complications:
- Know the risks of inhibitor formation and chronic joint damage.
- Differentials:
- Von Willebrand disease (consider if both aPTT and bleeding time are prolonged).