The autoimmune hemolytic anemias have been classified according to the temperature at which autoantibodies react with the red cell. This classification is particularly useful, since patients with cold antibodies will not benefit from splenectomy but those with warm antibodies may.
Although hemolysis without demonstrable antibody (Coombs test-negative) may occur in uremia, cirrhosis of the liver, cancer, and certain infections, in most cases the red cell membranes are coated with either immunoglobulin or complement (Coombs test-positive). The antibody in IgG autoimmune hemolytic anemia is specifically directed against the Rh locus. Initiation of this disease is either idiopathic or secondary to drug exposure, connective tissue disorders, or lymphoproliferative disorders. Cold agglutinin hemolytic anemia is due typically to an IgM, and hemolysis occurs intravascularly by complement fixation.
About 20% of cases of secondary immune hemolytic anemia are due to drug use, and hemolysis is usually mediated by warm antibodies. Penicillin, quinidine, hydralazine, and methyldopa have been most commonly implicated in this syndrome.
Disorders Associated with Immune Hemolysis.
Immune drug reaction (penicillin, quinidine, hydralazine, methyldopa, cimetidine)
Autoimmune hemolytic anemia may be encountered at any age but is common after age 50; it occurs often in women. The onset is usually acute, consisting of anemia, mild jaundice, and sometimes fever. The spleen is palpably enlarged in over 50% of patients, and pigment gallstones are present in about 25%.
Hemolytic anemia is diagnosed by demonstrating a normocytic normochromic anemia, reticulocytosis (over 10%), erythroid hyperplasia of the marrow, and elevation of indirect bilirubin. Stool urobilinogen may be greatly increased, but there is no bile in the urine. Serum haptoglobin is low. The direct Coombs test is positive because the red cells are coated with immunoglobulins or complement (or both).
Treatment of Autoimmune hemolytic anemia
Associated diseases must be carefully sought and appropriately treated. For drug-induced secondary hemolytic anemia, further exposure to the offending agent must be terminated. Corticosteroids produce a remission in about 75% of patients, but only 25% of remissions are permanent. Transfusion should be avoided if possible, since crossmatching may be extremely difficult, requiring washed red cells and saline-active antisera.
Splenectomy is indicated for patients who relapse after an initial response when steroids are withdrawn, and for patients in whom steroid therapy is contraindicated (eg, those with active pulmonary tuberculosis).
Splenectomy is effective because it removes the principal site of red cell destruction. Occasionally, splenectomy discloses the presence of an underlying disorder such as lymphoma. About half of patients who fail to respond to splenectomy will respond to azathioprine or cyclophosphamide. Plasmapheresis has been employed as salvage therapy of refractory hemolytic anemia.
Relapses may occur after splenectomy but are less frequent if the initial response was good. The ultimate prognosis in the secondary cases depends upon the underlying disorder.