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 in which 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 then remove portion of RBC membrane, forming a spherocyte because of decreased surface-to-volume ratio of the surviving RBC

  • Spherocytes are less deformable and become trapped in spleen

• Causes include

  • Systemic lupus erythematosus

  • Chronic lymphocytic leukemia

  • Lymphomas

  • Idiopathic (~50% of cases)

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

• Fludarabine, an antineoplastic, causes autoimmune hemolytic anemia through immunoincompetence; 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 is 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) is positive: patient's RBCs mixed with Coombs reagent; agglutination indicates IgG or both IgG and complement on RBC surface

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

• "Super-Coombs" 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, then Coombs reagent added; agglutination indicates presence of large amount of autoantibody that has saturated binding sites on RBCs 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 warm autoimmune hemolysis respond equally well to corticosteroids

• 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

  • Use with an anti-HBV agent if patient has history of hepatitis B viral infection

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