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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 in which IgG autoantibody binds to red blood cell (RBC) membrane protein

    • Macrophages in spleen and other portions of reticuloendothelial system then remove portion of RBC membrane, forming a spherocyte because of decreased surface-to-volume ratio of the surviving RBC

    • Spherocytes less deformable and become trapped in spleen

  • Causes include

    • Idiopathic (~50% of cases)

    • Systemic lupus erythematosus

    • Chronic lymphocytic leukemia

    • Lymphomas

  • Must be distinguished from drug-induced hemolytic anemia (eg, penicillin and other drugs, especially cefotetan, ceftriaxone, and piperacillin), which coats RBC membrane; autoantibody is directed against membrane–drug complex

  • Fludarabine, an antineoplastic, causes autoimmune hemolytic anemia through its immunosuppression; there is 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, angina pectoris, symptoms of heart failure

  • Jaundice and splenomegaly are usually present

Differential Diagnosis

  • Hereditary spherocytosis

  • Alloimmune transfusion reaction

  • Glucose-6-phosphate dehydrogenase deficiency

  • Microangiopathic hemolytic anemia

    • Thrombotic thrombocytopenic purpura

    • Hemolytic-uremic syndrome

    • Disseminated intravascular coagulation

  • Splenic sequestration

Diagnosis

Laboratory Tests

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

  • Reticulocytosis is present

  • Spherocytes on peripheral blood smear

  • Serum indirect bilirubin increased

  • Serum haptoglobin is low

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

  • Antiglobulin test is basis for diagnosis; reagent is rabbit IgM antibody against human IgG or human complement

  • Direct antiglobulin test (DAT) positive: patient's RBCs mixed with Coombs reagent; agglutination indicates antibody on RBC surface

  • DAT is positive (for IgG, complement, or both) in about 90% of patients

  • Indirect antiglobulin test may or may not be positive: patient's serum mixed with panel of type O RBCs, then Coombs reagent added; agglutination indicates presence of large amount of autoantibody that has saturated binding sites on RBC and consequently appears in serum

Treatment

Medications

  • Prednisone, 1–2 mg/kg/day orally in divided doses, is initial therapy

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

  • Danazol, 400–800 mg/day orally, is less effective than in immune thrombocytopenia

  • Rituximab

    • Dosage: 375 mg/m2 intravenously every week for 4 weeks, is effective and has low toxicity

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

  • Immunosuppressive agents (eg, cyclophosphamide, vincristine, azathioprine, cyclosporine, mycophenolate mofetil, alemtuzumab) may be effective

  • High-dose intravenous immune globulin (IVIG), 1 g/kg daily for 2 days

    • May be highly effective in controlling hemolysis

    • Benefit is short lived (1–3 weeks)

    • It is expensive

Surgery

  • Splenectomy

    • Should be considered if prednisone is ineffective or if disease recurs on tapering dose

    • May cure the disorder

Therapeutic Procedures
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