Autoimmune hemolytic anemia medical therapy

Corticosteroids

• Inhibition of IL-2 Inhibition of arachidonic acid production
• Inhibition of NF-kappaB signaling

• 70-85%
• Response usually occurs within 2 weeks^[1]

• Prednisone 1 to 1.5mg/kg PO daily for 1-3 weeks until hemoglobin improves to 10g/dl; rapid taper down to 20mg PO daily; slow taper over months from 20mg to 0mg
• Treat for 3-4 months with low-dose prednisone^[1]

• Immunosuppression
• Opportunisitic infection
• Bone density loss
• Loss of muscle mass
• Increased adipose deposition
• hypertension
• cataracts
• Glaucoma

• Extensive hepatic metabolism

• First-line therapy is co-administer calcium supplementation with vitamin D (for bone protection)
• Co-administer H2 receptor antagonist for GI protection if high risk for gastrointestinal bleeding

Azathioprine^[2]

• Purine synthesis inhibitor
• Converts to 6-mercaptopurine
• Antibody-dependent cell-mediated cytotoxicity

• 40-60%

• 1-3 mg/m2 IV weekly for 4 weeks

• Hepatitis B reactivation
• Progressive multifocal leukoencephalopathy

• Hepatic metabolism to 6-mercaptopurine and 6-thiouric acid

• Higher cost of therapy than corticosteroids

Rituximab^[3]

• CD20 monoclonal antibody
• Antibody-dependent cell-mediated cytotoxicity
• Depletion of B cells

• 83-87% overall response rate
• 54-60% complete response rate

• 375 mg/m2 IV weekly for 4 weeks
• 100 mg IV weekly for 4 weeks

• Hepatitis B reactivation
• Progressive multifocal leukoencephalopathy
• Infusion reaction

• Unknown

• Higher cost of therapy than corticosteroids

Mycophenolate mofetil

• Noncompetitive, selective, reversible inhibitor of inosine monophosphate (IMP) dehydrogenase
• Inhibits T cell proliferation by inhibiting purine synthesis

• Variable

• 1-1.5 g PO every 12 hours

• Hyperglycemia
• Hyperlipidemia
• Leukopenia
• Infections

• Enterohepatic recirculation to MPA, the active form of mycophenolate mofetil

• Higher cost of therapy than corticosteroids

Cyclosporine A

• Inhibits calcineurin-mediated NFAT dephosphorylation and activation (calcineurin inhibitor)
• Inhibits T cell proliferation

• Variable

• 1 mg/kg PO every 12 hours

• Tremor
• Nephrotoxicity
• Hypertension
• Infection
• Headache
• Gingival hyperplasia

• VIa hepatic CYP3A4 to metabolites AM1, AM9, and AM4N

• Nephrotoxicity limits its use in patients with renal dysfunction

Cyclophosphamide^[2]

• DNA alkylating agent
• Inhibits T cell proliferation

• Variable

• 50 mg/kg daily for 4 days

• Bone marrow suppression
• Nausea and vomiting
• Hemorrhagic cystitis
• Bladder cancer

• Hepatically metabolized to 4-hydroperoxycyclophosphamide and 4-aldophosphamide

• Chemotherapeutic agent