A u t o i m m u n e H e m o l y t i c A n e m i a
Two kinds: Warm and Cold.
Warm autoimmune hemolytic anemia (AIHA)
Causes
• Primary/idiopathic (2/3 of cases)
• Secondary to:
1. Lymphoma/leukemia
2. Other malignancies
3. Autoimmune disorders
4. Infections
5. Drugs (methyl-dopa, penicillin)
Pathogenesis
• IgG Ab (to Rh blood group Ag, to a drug, etc.).
• Binds to red cell best at 37 C.
• Macrophages in spleen nibble out bits of the IgG-coated red cells, which
become spherocytes. Spleen eventually eats up the spherocytes entirely.
Clinical Features
• Any age, either sex.
• Variably severe anemia.
• Splenomegaly.
Morphology
• Prominent spherocytosis.
• Other signs of hemolysis (polychromasia, normoblasts).
Diagnosis
• Use direct antiglobulin test (DAT; also called Coombs test)
This test uses animal anti-IgM, -IgG, etc. to look for Ab bound to red cells.
• Positive result is strong evidence for an immune process.
• Very rarely, patients with AIHA have so little Ab bound to red cells that the
DAT cannot detect it, leading to a false negative result.
• Patients with warm AIHA usually are positive for IgG.
Treatment
• Treat underlying cause, if there is one.
• Give steroids.
• Splenectomy.
Cold autoimmune hemolytic anemia (AIHA)
Causes
• Primary/idiopathic (Ab often monoclonal!)
• Secondary to:
1. Infections
• Mycoplasma pneumoniae (most common).
• Infectious mononucleosis.
• Ab usually polyclonal.
• Usually self-limited.
2. Lymphoproliferative disorders
• Ab usually monoclonal (because it's coming from a clonal population of
lymphoid cells, which all produce exactly the same kind of antibody,
e.g., IgG - kappa)
Pathogenesis
• IgM (usually against "I" antigen on red cell surface), complement.
• Bind to red cell best at 4 C (in distal, colder body parts).
• IgM causes agglutination (bridges adjacent red cells), but falls off in warmer
body parts.
• Complement stays on red cell; causes:
• Intravascular hemolysis (via complement cascade)
• Extravascular hemolysis (Liver, and to lesser extent, spleen, gobble up
C'-coated red cells)
Clinical Features
• Idiopathic type and lymphoproliferative-disorder-related type: mostly elderly
patients.
• Infection-related type: younger and older patients.
• Chronic, usually mild hemolytic anemia aggravated by the cold.
• Pallor/cyanosis in colder body parts (vascular obstruction from red cell
agglutinates).
Morphology
• Red blood cell agglutination (large clumps) on blood smears made at room
temperature.*Note: unless the blood specimen is warmed before running
through machine, RBC will be off (low).
• Spherocytes present, but less numerous than in warm AIHA.
• Other signs of hemolysis (polychromasia, normoblasts).
Diagnosis
• Use DAT (see above)
• Patients with cold AIHA usually are positive for IgM and complement.
Treatment
• Treat underlying cause, if there is one.
• Keep patient warm.
• Splenectomy and steroids not helpful.
