Anemia, Autoimmune Hemolytic

Key Features

Essentials of Diagnosis

• Pallor, fatigue, jaundice, and dark urine

• Splenomegaly

• Positive direct antiglobulin test

• Reticulocytosis and spherocytosis

General Considerations

• One of the more common causes of acute anemia after the first year but rare during first 4 months of life

• May arise as a primary disorder

• May complicate

  • An infection (hepatitis, upper respiratory tract infections, Epstein-Barr [EBV] mononucleosis, or cytomegalovirus [CMV] infection)

  • Systemic lupus erythematosus and other autoimmune syndromes

  • Immunodeficiency states, including autoimmune lymphoproliferative syndrome (ALPS)

  • Malignancies, albeit very rarely

• Drugs may induce antibody-associated hemolytic anemia

• Third-generation cephalosporins have become a common cause

Clinical Findings

• Onset is usually sudden manifested by weakness, pallor, dark urine, and fatigue

• However, in some cases, onset can be more gradual and insidious

• Jaundice is a prominent finding

• Splenomegaly is often present

• Clinical evidence of an underlying disease may be present

Diagnosis

• Anemia is normochromic and normocytic and may vary from mild to severe (hemoglobin concentration < 5 g/dL)

• Reticulocyte count and index are usually increased but occasionally are normal or low

• Spherocytes and nucleated red cells may be seen on the peripheral blood smear

• Although leukocytosis and elevated platelet counts are common, thrombocytopenia occasionally occurs

• Intravascular hemolysis is indicated by hemoglobinemia or hemoglobinuria

• Examination of bone marrow shows marked erythroid hyperplasia and hemophagocytosis, but is seldom required for the diagnosis

• In almost all cases, the direct and indirect antiglobulin tests are positive

Treatment

• Warm autoimmune hemolytic anemia (AIHA) (in which hemolysis is mostly extravascular)

  • Most patients (50–80%) respond to prednisone (2 mg/kg/d)

  • Patients may respond to intravenous immune globulin (IVIg) 1 g/kg/d for 2 days

  • Rituximab

    • May be a successful alternative in severe cases

    • However, should be avoided when anemia is associated with ALPS

  • Splenectomy

    • Remission with splenectomy may be as high as 50–60%

    • However, should be considered only for patients older than 5 years who are refractory or resistant to first-line therapies

  • In cases unresponsive to more conventional therapy, following immunosuppressive agents may be tried alone or in combination with corticosteroids

    • Mycophenolate

    • Sirolimus

    • Cyclosporine

    • Cyclophosphamide

    • Azathioprine

    • Busulfan.

  • Transplantation, especially when hemolysis is secondary, has been used successfully in small numbers of cases

• Cold AIHA and paroxysmal cold hemoglobinuria

  • Less likely to respond to corticosteroids or IVIg

  • Supportive care alone may be sufficient since these syndromes are most apt to be associated with infections and have an acute, self-limited course

  • Plasma exchange may be effective in severe cold (IgM) AIHA because the offending antibody has an intravascular distribution

  • Transfusion

    • May be necessary because of the complications of severe anemia

    • Should be used only when there is no alternative

  • Heparin should be considered in patients with severe intravascular hemolysis who may have associated disseminated intravascular coagulation

Outcome

Complications