Hemophilia

Etiology

• X-linked recessive inheritance (males affected; females typically asymptomatic carriers). c
• Hemophilia A (factor VIII deficiency): ∼ 80% of cases
• Hemophilia B (factor IX deficiency): ∼ 20% of cases
• Hemophilia C (factor XI deficiency): very rare

Clinical features

1. Repeated hemarthrosis (e.g., knee joint) → hemophilic arthropathy (i.e., destruction of the joint due to repeated hemarthrosis)
2. Oral mucosa bleeding, epistaxis, excessive bleeding following small procedures (e.g., dentist procedures)
3. Hemophilia C does not typically manifest with spontaneous bleeding, hemarthrosis, or deep tissue bleeding.

Management

• Acute Bleeding Episodes:
  1. Immediate Factor Replacement (First-Line):
     • Major/life-threatening bleed (ICH, trauma, retroperitoneal): Target 100% factor activity immediately before obtaining diagnostic imaging.
     • Moderate/minor bleed (early hemarthrosis): Target 40–50% factor activity.
     • Hemophilia A $\to$ Recombinant Factor VIII.
     • Hemophilia B $\to$ Recombinant Factor IX (Note: DDAVP is ineffective for Hemophilia B).
  2. Mild Hemophilia A (Minor Bleeds / Pre-procedural Prophylaxis):
     • Desmopressin (DDAVP): Stimulates release of endogenous vWF and FVIII from Weibel-Palade bodies.
     • Antifibrinolytics (Aminocaproic acid, Tranexamic acid): Useful adjuncts for oral/mucosal bleeding (contraindicated in upper urinary tract hematuria due to ureteral obstruction risk).
• Chronic Prophylaxis:
  • Scheduled IV factor concentrate infusions 2–3 times weekly to maintain trough levels >1%.
  • Emicizumab: Bispecific monoclonal antibody mimicking FVIII by bridging FIXa and FX (used for Hemophilia A prophylaxis with or without inhibitors).
• Refractory Bleeding / Inhibitor Development:
  • Occurs when pts develop neutralizing IgG alloantibodies against exogenous factor infusions.
  • Bypassing Agents: Recombinant Factor VIIa (rFVIIa) or Activated Prothrombin Complex Concentrate (aPCC / FEIBA).