Autoimmune hemolytic anemia

Background

• Autoimmune hemolytic anemia (AIHA) = generation of auto-antibodies towards red blood cell membrane antigens, leady to hemolysis.
• Can be primary (idiopathic) or due to another disease process (e.g. malignancy, autoimmune disease, infection)

"Warm" Autoimmune Hemolytic Anemia

Autoantibodies agglutinate to RBCs at higher temperatures

• IgG mediated, usually pan-reactive to patient's and transfused RBCs
• Extravascular (i.e. in spleen) hemolysis→ unconjugated > conjugated hyperbilirubinemia
• Haptoglobin low, LDH may be normal
• Causes:
  • Lymphoma, especially Non-Hodgkin's lymphoma
  • Leukemia, particularly chronic lymphocytic leukemia
  • Collagen vascular diseases (E.g. Systemic Lupus Erythematosus, Rheumatoid arthritis, Giant cell arteritis
  • Viral-induced or HIV-associated
  • Medications: methyldopa, quinidine, penicillin

"Cold" Autoimmune Hemolytic Anemia

Autoantibodies agglutinate at lower temperatures

• IgM mediated
• Intravascular hemolysis→ high LDH, low haptoglobin, hemoglobinuria
• Causes:
  • Infection, most commonly Mycoplasma pneumoniae and mononucleosis, also varicella, listeria, influenza
  • Multiple myeloma and other plasmacytomas
  • Idiopathic

Clinical Features

• Signs and symptoms of anemia (fatigue, pallor, palpitations, etc.)
• Jaundice and scleral icterus
• Signs/symptoms of underlying disease process
• Cold-type:
  • Acrocyanosis, Raynaud's, vascular occlusion with peripheral tissue ischemia

Differential Diagnosis

Anemia

RBC Loss

• Hemorrhage

RBC consumption (Destruction/hemolytic)

• Hereditary
• Acquired
• Microangiopathic Hemolytic Anemia (MAHA)
• Autoimmune hemolytic anemia

Impaired Production (Hypochromic/microcytic)

• Iron deficiency
• Anemia of chronic disease
• Thalassemia
• Sideroblastic anemia

Aplastic/myelodysplastic (normocytic)

• Marrow failure
• Chemicals (e.g. ETOH)
• Radiation
• Infection (HIV, parvo)

Megaloblastic (macrocytic)

• Vitamin B12/folate deficiency
• Drugs (chemo)
• HIV

Evaluation

• CBC, LFTs, LDH, haptoglobin
• Direct Coombs test - blood sample is removed of plasma and incubated with anti-human immunoglobulin (aka "Coombs reagent"). This detects if autoantibodies are attached to RBCs or compliment. If the RBCs are coated with IgG (positive direct Coombs test), this suggests the diagnosis of "warm AIHA. If the RBCs are coated with only compliment, this suggests the diagnosis of "cold" AIHA

Management

Warm AIHA

• Oral prednisone 1-1.5mg/kg/day for 1-3 weeks with taper after hemoglobin stable
  • may need several months of low dose prednisone to remain in remission
• Splenectomy and/or cytotoxic drugs for for steroid-refractory disease
• Plasmapheresis as temporizing measure for severe disease
• Transfuse pRBCs only if truly life-threatening anemia, least incompatible units possible

Cold AIHA

• No treatment for mild disease
• Immunosuppressive or cytotoxic medications can be considered
• Plasmapheresis for severe disease

See Also

• Paroxysmal nocturnal hemoglobinuria (PNH)
• Systemic lupus erythematosus
• Rheumatoid arthritis
• Scleroderma