Haemophilia Summary

Types & Inheritance

  • Haemophilia A: Factor VIII deficiency
  • Haemophilia B: Factor IX deficiency
  • Inheritance: X-linked recessive
  • Acquired: Autoimmune, non-inherited

Inheritance Pattern

  • Males exclusively affected (congenital)
  • Female carriers may have symptoms
  • 1/3 cases: No family history (new mutations)

Clinical Features

  • Prolonged bleeding after trauma/surgery
  • Spontaneous joint bleeds (hemarthrosis)
  • Muscle hematomas
  • Severity correlates with factor levels

Severity Classification

  • Severe: <1% factor activity
  • Moderate: 1-5% factor activity
  • Mild: 5-40% factor activity

Treatment

  • Factor replacement therapy
  • Prophylactic vs. on-demand treatment
  • Desmopressin for mild Haemophilia A
  • Antifibrinolytics (tranexamic acid)

Complications

  • Inhibitor development
  • Joint arthropathy
  • Chronic pain
  • Transfusion-transmitted infections

Emergency Management

  • Immediate factor replacement
  • Avoid NSAIDs, IM injections
  • Head injury: Treat as emergency
  • Surgical cover with factor concentrate

Haemophilia

X-linked bleeding disorder resulting from coagulation factor deficiencies

Overview

Haemophilia is a bleeding disorder, usually inherited with an X-linked recessive inheritance pattern, which results from the deficiency of a coagulation factor.

Haemophilia A

  • Deficiency of clotting factor VIII
  • More common (80-85% of cases)
  • Incidence: 1 in 5,000 male births

Haemophilia B

  • Deficiency of clotting factor IX
  • Also known as Christmas disease
  • Incidence: 1 in 30,000 male births

Acquired Haemophilia

  • Separate non-inherited condition
  • Much rarer than congenital haemophilia
  • Autoimmune-related aetiology
  • No genetic inheritance pattern

Inheritance Pattern

Congenital haemophilia has an X-linked recessive pattern of inheritance. Therefore, boys/men are exclusively affected, although many female carriers have clotting factor levels in the haemophilia range due to lyonization (random inactivation of the normal X chromosome) and may have bleeding symptoms requiring appropriate management.

Important: Up to one third of patients with congenital haemophilia have no family history, as the condition may also result from spontaneous germline mutations and/or somatic mosaicism during early embryogenesis.

X-linked Recessive Inheritance

Female Carrier × Normal Male

  • Sons: 50% chance of developing disease
  • Daughters: 50% chance of being carrier

Male Haemophiliac × Normal Female

  • Sons: All unaffected
  • Daughters: All carriers

Carrier Status and Lyonization

Lyonization: Random X-chromosome inactivation in females means some carriers may have factor levels low enough to cause bleeding symptoms. Carrier females typically have 30-70% of normal factor levels, but some may have levels in the mild haemophilia range (<40%).

Clinical Features

Bleeding Manifestations

Severe Haemophilia (<1% factor)

  • Spontaneous bleeding into joints (hemarthrosis)
  • Muscle hematomas
  • Prolonged bleeding after minor trauma
  • Life-threatening bleeding (CNS, neck, GI)

Moderate Haemophilia (1-5% factor)

  • Bleeding with mild trauma
  • Occasional spontaneous bleeding
  • Less frequent joint bleeds

Mild Haemophilia (5-40% factor)

  • Bleeding only with significant trauma/surgery
  • Often undiagnosed until adulthood
  • May present with surgical bleeding

Common Bleeding Sites

Site Clinical Features Complications
Joints (Hemarthrosis) Knees, elbows, ankles most common; pain, swelling, warmth Chronic arthropathy, joint deformity
Muscles Iliopsoas, forearm, calf; pain, swelling, compartment syndrome Contractures, nerve compression
CNS Head trauma, spontaneous intracranial hemorrhage Neurological deficit, death
Mucosal Epistaxis, gum bleeding, GI bleeding Anemia, rarely life-threatening

Diagnosis

Diagnostic Approach
  1. Clinical suspicion: Unexplained bleeding, family history
  2. Screening tests:
    • PT: Normal
    • aPTT: Prolonged
    • Platelet count: Normal
    • Bleeding time: Normal
  3. Specific factor assays: Factor VIII or IX levels
  4. Genetic testing: Mutation analysis, carrier detection

Differential Diagnosis

  • Von Willebrand disease (more common in females)
  • Other coagulation factor deficiencies
  • Platelet function disorders
  • Vitamin K deficiency
  • Liver disease

Management

Factor Replacement Therapy

Haemophilia A

  • Recombinant factor VIII concentrate (preferred)
  • Plasma-derived factor VIII
  • Dosing: 25-50 IU/kg depending on bleed severity

Haemophilia B

  • Recombinant factor IX concentrate
  • Plasma-derived factor IX
  • Dosing: 40-80 IU/kg depending on bleed severity

Treatment Strategies

Strategy Indication Regimen
Prophylaxis Severe haemophilia, children Regular factor infusions (2-3 times/week for HA, 1-2 times/week for HB)
On-demand Mild/moderate haemophilia, bleeding episodes Factor infusion at time of bleed
Immune tolerance Inhibitor development High-dose frequent factor administration

Adjunctive Therapies

  • Desmopressin (DDAVP): For mild Haemophilia A - releases stored vWF and FVIII
  • Antifibrinolytics: Tranexamic acid, aminocaproic acid - for mucosal bleeding
  • Topical agents: Fibrin sealants, topical thrombin

Complications

Inhibitor Development

  • Alloantibodies against infused factor
  • Occurs in 20-30% of severe Haemophilia A patients
  • Less common in Haemophilia B (1-3%)
  • Makes treatment challenging and expensive

Joint Disease

  • Chronic hemophilic arthropathy
  • Pain, limited mobility, joint deformity
  • May require joint replacement surgery
  • Physiotherapy essential

Other Complications

  • Transfusion-transmitted infections (historical)
  • Iron overload from repeated transfusions
  • Psychosocial impact of chronic disease
  • Financial burden of treatment

Emergency Management

Life-threatening bleeds require immediate factor replacement and specialist hematology input.

Critical Bleeding Scenarios

Situation Immediate Action
Head injury (any severity) Immediate factor infusion, CT head, admit for observation
Neck or throat bleeding Airway protection, immediate factor infusion
Major trauma/surgery Factor infusion to achieve 80-100% levels
Joint bleed Factor infusion, RICE (rest, ice, compression, elevation)
Minor cuts Pressure, topical agents, antifibrinolytics

Medications to Avoid

  • Aspirin and NSAIDs: Impair platelet function
  • Intramuscular injections: Risk of hematoma formation
  • Herbal supplements: Some may affect coagulation