Autoimmune hemolytic anemia

• These come from anti-RBC Abs

• A (+) direct Coomb’s test indicates the presence of RBC-bound immunoglobins (an indirect Coomb’s test looks for these AB in the serum)

• Warm Ab type

  • Idiopathic (1°) in 50% of patients; the other 50% is associated with drug exposure (e.g., quinidine, -methyl dopa, penicillin, cephalosporins), lymphoma or leukemia (will see monoclonal Abs), carcinoma, or an autoimmune syndrome (especially SLE)

  • Abs are IgG, active at 37°C, and do not fix complement

  • Hemolysis is extravascular from the spleen destroying RBCs coated with Abs; spherocytosis and splenomegaly (from RES hyperplasia) may be present

  • Possible mechanisms for drug-induced hemolysis

    • Hapten model: Ab directed against drug/RBC membrane complex

    • Immune complex model: Ab directed against drug/plasma protein complex which cross reacts with RBC membrane Ag

    • AutoAb model: autoAbs directed against intrinsic RBC membrane Ags

• Cold agglutinin type

  • AutoAbs are IgM, bind to RBCs at low temps (0-4°C) and cause RBC agglutination (this screws up the rule of 3’s; MCHC will also be screwed up…will see increased WBCs [because the agglutinated RBCs register as WBCs], decreased RBCs, and no change in Hb – sample must be reheated to 37°C before analysis)

  • Seen acutely with infection with Mycoplasma pneumoniae (Abs directed against I-blood group Ag) and EBV (Abs against i-blood group Ag); hemolysis is usually minimal and self-limited

  • Chronic disease may be seen with Hep-C infection, in lymphoproliferative syndromes (Abs will be monoclonal), or may be idiopathic; hemolysis and resultant anemia are variable

  • Exposure to cold temperatures can lead to agglutination and subsequent vascular obstruction (Raynaud’s phenomenon)

  • Paroxysmal cold hemoglobinuria

    • Causes acute intermittent massive hemolysis with cold exposure

    • IgG autoAb are directed against the P-blood group Ag and bind complement at low temperatures

    • At 37°C, the Abs are released, but complement activation and intravascular hemolysis occur; this biphasic Ab is referred to as the Donath-Landsteiner Ab (used to be associated with syphilis; now seen with measles, mumps, Mycoplasma pneumoniae, and ill-defined viral illnesses)

    • Usually self-limited

    • Attacks are associated with hemoglobinuria, muscle pain, and F

    • Erythrophagocytosis by neutrophils may be seen in peripheral smears

Category: Medical Subject Notes , Pathology Notes