Immune-mediated thrombocytopenic purpura

Background

• Acquired autoimmune bleeding disorder characterized by autoimmune autobody-mediated destruction of platelets

Etiology

• Primary
• Secondary
  • Infection
    • HIV
    • Hepatitis C virus
    • CMV
    • VZV
    • Helicobacter pylori
  • Inflammatory/Autoimmune
    • Antiphospholipid antibody syndrome
    • Autoimmune thrombocytopenia (Evans syndrome)
  • Congenital: common variable immune deficiency
  • Neoplasm: lymphoproliferative disorder
  • Medications

Investigations

• CBC
  • Mean platelet volume can suggest high platelet turnover
• Peripheral blood film
• HIV and HCV testing
• Additional
  • Abdo ultrasound for splenomegaly and liver disease
  • Rh status
  • DAT for Evan's syndrome
  • Quantitative immunoglobulins
  • Hep B testing
  • H. pylori, if at risk
  • Antiphospholipid antibodies
  • ANA, anti-dsDNA
  • Thyroid tests
  • vWF testing (for type 2B vWD)
  • Bone marrow biopsy

Management

Acute management

• Only needs treatment if platelets lower than 30 or if bleeding
• First-line:
  • Steroids
    • Prednisone 1-2mg/kg/day x3weeks then taper (70-80% response but high relapses over next 10 years)
    • Dexamethasone 40mg/d po x4days ever 2-4 weeks, repeated for 3-6 cycles (90% response)
  • IVIg 1-2g/kg x1-2 days, if refractory to steroids or requires rapid treatment
  • Anti-D if Rh positive and has a spleen
• Second-line:
  • Splenectomy
    • Ensure vaccinated for Hib, Strep pneumo, and N. meningitidis
  • Rituximab
  • Thrombopoeitin agonists: eltrombopag or romiplostim
  • Immunosuppressive therapies: azathioprine, cyclosporin A, cyclophosphomide, danazol, dapsone, mycofenolate mofetil, vina alkaloids
• Third-line:
  • Almtuzumab, chemotherapy, stem cell transplant
• For life-threatening bleed:
  • IVIG 1g/kg, repeated once more if platelets remain below 50 the next day
  • Pulse steroids: methylprednisolone 30mg/kg IV daily x2-3 days)
  • Tranexamic acid 1G IV q6h
  • Platelet transfusion
  • Emergency splenectomy
  • Last-ditch: recombinant factor VIIa 90mcg/kg IV q2h
    • High risk for clotting