IMMUNE HEMOLYTIC ANEMIA
Hemolytic anemias can result from exposure of the RBC to anti-bodies. Alloantibodies (ie, antibodies against the host, or “self”) re-sult from the immunization of an individual with foreign antigens (eg, the immunization of an Rh-negative person with Rh-positive blood). Alloantibodies tend to be large (IgM type) and cause im-mediate destruction of the sensitized RBCs, either within the blood vessel (intravascular hemolysis) or within the liver. The most com-mon type of alloimmune hemolytic anemia in adults results from a hemolytic transfusion reaction.
Autoantibodies are developed by an individual for varying rea-sons. In many instances, the person’s immune system is dysfunc-tional, so that it falsely recognizes its own RBCs as foreign and produces antibodies against them. This mechanism is seen in peo-ple with chronic lymphocytic leukemia (CLL). Another mecha-nism is a deficiency in suppressor lymphocytes, which normally prevent antibody formation against a person’s own antigens. Auto-antibodies tend to be of the IgG type. The RBCs are sequestered in the spleen and destroyed by the macrophages outside the blood vessel (extravascular hemolysis).
Autoimmune hemolytic anemias can be classified based on the body temperature involved when the antibodies react with the RBC antigen. Warm-body antibodies bind to RBCs most actively in warm conditions (37°C); cold-body antibodies react in cold (0°C). Most autoimmune hemolytic anemias are the warm-body type. Autoimmune hemolytic anemia is associated with other dis-orders in most cases (eg, medication exposure, lymphoma, CLL, other malignancy, collagen vascular disease, autoimmune disease, infection). In idiopathic autoimmune hemolytic states, the reason why the immune system produces the antibodies is not known. All ages and genders are equally vulnerable to this form, whereas the incidence of secondary forms is greater in people older than 45 years of age and in females.
Clinical manifestations can vary, and they usually reflect the degree of anemia. The hemolysis may be very mild, so that the patient’s marrow compensates adequately and the patient is asymptomatic. At the other extreme, the hemolysis can be so severe that the resultant anemia is life-threatening. Most patients complain of fatigue and dizziness. Splenomegaly is the most common physical finding, occurring in more than 80% of patients; hepatomegaly, lym-phadenopathy, and jaundice are also common.
The laboratory tests show a low hemoglobin level and hematocrit, most often with an accompanying increase in the reticulocyte count. RBCs appear abnormal; spherocytes are common. The serum bilirubin level is elevated, and if the hemolysis is severe, the haptoglobin level is low or absent. The Coombs test (also referred to as the direct antiglobulin test [DAT]), which detects antibodies on the surface of RBCs, shows a positive result.
Any possibly offending medication should be immediately dis-continued. The treatment consists of high doses of corticosteroids (1 mg/kg per day) until hemolysis decreases. Corticosteroids de-crease the macrophage’s ability to clear the antibody-coated RBCs. If the hemoglobin level returns toward normal, usually after sev-eral weeks, the corticosteroid dose can be lowered or, in some cases, tapered and discontinued. However, corticosteroids rarely produce a lasting remission. In severe cases, blood transfusions may be required. Because the antibody may react with all possible donor cells, careful blood typing is necessary, and the transfusion should be administered slowly and cautiously.
Splenectomy (removal of the spleen) removes the major site of RBC destruction; therefore, splenectomy may be performed if corticosteroids do not produce a remission. If neither cortico-steroid therapy nor splenectomy is successful, immunosuppressive agents may be administered. The two immunosuppressive agents most frequently used are cyclophosphamide (eg, Cytoxan), which has a more rapid effect but more toxicity, or azathioprine (Imu-ran), which has a less rapid effect but less toxicity. The synthetic androgen danazol (Cyclomen, Danocrine) can be useful in some patients, particularly in combination with corticosteroids. The mechanism for this success is unclear. If corticosteroids or im-munosuppressive agents are used, the taper must be very gradual to prevent a rebound “hyperimmune” response and exacerbation of the hemolysis. Immunoglobulin administration is effective in about one third of patients, but the effect is transient and the med-ication is expensive. Transfusions may be necessary if the anemia is severe; it may be extremely difficult to cross-match samples of available units of RBCs with that of the patient.
For patients with cold-antibody hemolytic anemia, treatment may not be required, other than to advise the patient to keep warm; relocation to a warm climate may be necessary.
Patients may have great difficulty understanding the pathologic mechanisms underlying the disease and need repeated explana-tions in terms they can understand. Patients who have had a splenectomy should be vaccinated against pneumococcal infec-tions (Pneumovax) and informed that they are permanently at greater risk for infection. Patients receiving long-term cortico-steroid therapy, particularly those with concurrent diabetes or hy-pertension, need careful monitoring. They must understand the need for this medication and the importance of never abruptly dis-continuing it. A written explanation and a tapering schedule should be provided, and adjustments based on hemoglobin levels should be emphasized. Similar teaching should be provided when immunosuppressive agents are used. Corticosteroid therapy is not without significant risk, and patients need to be monitored closely for complications. The short- and long-term complications of cor-ticosteroid therapy are presented in Chart 33-4.
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