---

Hemophilia

Overview

• Hemophilias are the commonest hereditary clotting disorders
• Both Hemophilia A and B are inherited in an X-linked recessive manner
• Hemophilia A - Factor VIII deficiency
• Hemophilia B - Factor IX deficiency
• Clinical manifestations are indistinguishable; presentation depends on the level of factor present

Clinical Features

• Delayed bleeding after tooth extraction or minor surgery - prolonged, severe, not controlled without clotting factor replacement
• Factor levels <1%: repeated, spontaneous, debilitating joint bleeds → permanent disability
• Intracranial bleeds can be life-threatening

Factor Level Classification

---

Laboratory Investigation

• Different clotting disorders can have very similar symptoms
• Accurate diagnosis requires PT and APTT
• In Hemophilia A and B: APTT is prolonged
• Specific factor assay for factor VIII or IX reveals the deficient clotting factor

---

Complications

• Recurrent joint and muscle bleeds → permanent disability
• Life-threatening sites: CNS, neck, iliopsoas muscle
• Shock from large bleeds
• Most serious complication: development of inhibitors (alloantibodies to clotting factor) → makes clotting factors ineffective

---

Management

• Managed at specialized centers
• Factor VIII or IX concentrates available
  • 1 unit factor VIII/kg → raises level by 2%, half-life 8-12 hours
  • 1 unit factor IX/kg → raises level by 1%, half-life 24 hours

Target Factor Levels for Treatment:

Other Products:

• Cryoprecipitate - contains Factor VIII, fibrinogen, von Willebrand factor (NOT Factor IX)
• Fresh Frozen Plasma (FFP) - retains all factors including labile V and VII
• Both cryoprecipitate and FFP are only for emergencies or unknown diagnosis
• Epsilon-aminocaproic acid / Tranexamic acid - adjunct in mild cases
• Emicizumab - non-factor monoclonal antibody, effective in Hemophilia A with or without inhibitors; given subcutaneously every 1-4 weeks

---

Management of Hemophilia with Inhibitors

• Patients will NOT respond to clotting factor VIII/IX, FFP, or cryoprecipitate
• Require bypassing agents:
  • Recombinant activated factor VIIa (Novoseven)
  • Factor VIII inhibitor bypass activated prothrombin complex - FEIBA
• Inhibitors may be eradicated by immune tolerance induction - repeated/frequent administration of Factor VIII → downregulates antibody response
• Newer agents being tested: concizumab, fitusiran

---

Prophylaxis

• Children with severe hemophilia: factor replacement 2-3 times/week
• Factor VIII: 15-20 IU/kg three times/week for Hemophilia A
• Extended half-life products can further reduce frequency
• Results in less deformity, better quality of life

---

Additional Recommendations

• All children should receive Hepatitis B immunizations (subcutaneous route)
• Parents counseled regarding injury prevention
• Genetic counseling required; families informed of prenatal diagnosis availability