Factor VIII inhibitor

Background

• Autoantibodies (IgG) directed against Factor VIII, causing an acquired coagulopathy
• Also called acquired hemophilia A — distinct from congenital hemophilia
• Rare but potentially life-threatening; mortality 8-22%
• Associations: autoimmune diseases, malignancy, pregnancy/postpartum, medications (penicillin, sulfonamides), idiopathic (~50%)
• Most common in elderly patients (median age 60-70)

Clinical Features

• Spontaneous soft tissue bleeding, ecchymoses, hematomas (often extensive)
• Mucosal bleeding, GI bleeding, hematuria
• Unlike congenital hemophilia: hemarthrosis is uncommon
• May present with life-threatening hemorrhage without prior bleeding history

Differential Diagnosis

Coagulopathy

Platelet Related

• Too few
  • Thrombocytopenia
• Nonfunctional
  • Aspirin
  • Von Willebrand disease

Factor Related

• Acquired (Drug Related)
  • Warfarin (Coumadin)
  • Unfractionated heparin
  • Low molecular weight heparin (i.e. enoxaparin (Lovenox), dalteparin)
  • Factor Xa Inhibitors (e.g. rivaroxaban, apixaban, fondaparinux, edoxaban)
  • Direct thrombin inhibitors (e.g. dabigatran, argatroban, bivalirudin)
• Illness induced
  • Vitamin K deficiency
  • Disseminated Intravascular Coagulation (DIC)
  • Liver disease induced coagulopathy
  • Uremic bleeding syndrome
• Genetic
  • Hemophilia
  • Factor VIII inhibitor
  • Lupus anticoagulant

Evaluation

• Isolated prolonged PTT with normal PT and platelet count
• Mixing study: PTT does NOT correct (distinguishes inhibitor from factor deficiency)
• Factor VIII activity level markedly reduced
• Bethesda assay: Quantifies inhibitor titer (Bethesda Units)
• CBC, fibrinogen, DIC panel to assess for concurrent coagulopathy

Management

• Acute bleeding:
  • Bypassing agents (first-line for significant hemorrhage):
    • Recombinant Factor VIIa (NovoSeven) 90 mcg/kg IV q2-3h
    • Activated prothrombin complex concentrate (FEIBA) 50-100 units/kg IV q8-12h
  • High-dose Factor VIII concentrate may be tried but often ineffective if high-titer inhibitor
  • Desmopressin (DDAVP) for low-titer inhibitors only
• Inhibitor eradication (in consultation with hematology):
  • Immunosuppression: corticosteroids ± cyclophosphamide
  • Rituximab for refractory cases
• Avoid procedures and IM injections; hold anticoagulants

Disposition

• Admit all patients — hematology consult urgently
• ICU for significant hemorrhage

See Also

• Hemophilia
• Coagulopathy (Main)
• DIC