Anemia, Autoimmune Hemolytic

KEY FEATURES

Essentials of Diagnosis

• Acquired hemolytic anemia caused by immunoglobulin G (IgG) autoantibody

• Spherocytes and reticulocytosis on peripheral blood smear

• Positive antiglobulin (Coombs) test

General Considerations

• Acquired disorder

  • IgG autoantibody binds to red blood cell (RBC) membrane protein at body temperature (ie, a "warm autoantibody")

  • Macrophages in spleen and other portions of reticuloendothelial system

    • Remove portion of RBC membrane

    • Form a spherocyte because of decreased surface-to-volume ratio of the surviving RBC

    • Spherocytes are less deformable and become trapped in spleen

  • The destruction of RBCs in the spleen and liver designates this as extravascular hemolysis

• Causes include

  • Systemic lupus erythematosus

  • Chronic lymphocytic leukemia

  • Lymphomas

  • Idiopathic (∼50% of cases)

• Must be distinguished from drug-induced hemolytic anemia

  • A drug coats the RBC membrane eg,

    • Penicillin

    • Cefotetan

    • Ceftriaxone

    • Piperacillin

  • An autoantibody is directed against the membrane–drug complex (ie, the hemolysis is hapten-mediated)

• Fludarabine, an antineoplastic

  • Causes autoimmune hemolytic anemia through immunoincompetence

  • Defective self-vs-non–self-immune surveillance

• Typically produces anemia of rapid onset that may be life-threatening

CLINICAL FINDINGS

Symptoms and Signs

• Fatigue

• Dyspnea

• Symptoms of angina pectoris, heart failure may occur

• Symptoms of central nervous system ischemia can be seen

• Jaundice and splenomegaly are usually seen

• Splenomegaly

DIAGNOSIS

Laboratory Tests

• Anemia of variable degree; hematocrit may be < 10% in more severe cases

• Reticulocytosis is present

• Spherocytes on peripheral blood smear

• In severe hemolysis, stressed bone marrow may release nucleated RBCs

• Serum indirect bilirubin is increased

• Serum haptoglobin is low

• Coincident immune thrombocytopenia (Evans syndrome) in ∼10%

• Antiglobulin (Coombs) test is basis for diagnosis

  • Coombs reagent is rabbit IgM antibody against human IgG or human complement

• Direct antiglobulin test (DAT) is positive

  • Patient's RBCs mixed with Coombs reagent

  • Agglutination indicates IgG or both IgG and complement on RBC surface

  • For IgG, complement, or both in about 90% of patients

  • "Super-Coombs" test might be positive in some of the 10% negative group

• Indirect antiglobulin test may or may not be positive

  • Patient's serum mixed with panel of type O RBCs

  • Coombs reagent added

  • Agglutination indicates presence of large amount of free antibody(autoantibody or alloantibody)

TREATMENT

Medications

• Prednisone, 1–2 mg/kg/d orally for several weeks, followed by a slow taper, is initial therapy

• Patients with DAT-positive and DAT-negative warm autoimmune hemolysis respond equally well to corticosteroids

• Rituximab

  • Dosage: 375 mg/m² intravenously every week for 4 weeks

  • In severe disease, used in conjunction with corticosteroids as initial therapy

  • If past history of hepatitis B viral (HBV) infection

    • Use with an anti-HBV agent to prevent (sometimes fatal) reactivation of quiescent hepatitis B

• Danazol, 400–800 mg/day orally

  • Less effective than in immune thrombocytopenia

  • Has low toxicity profile

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