APLASTIC ANEMIA

Differential Diagnosis

This anemia is associated with a decreased bone marrow mass, a borderline high MCV, leukopenia, and thrombocytopenia. Pure red blood cell aplasia is the term given when only the erythroid line of cells is affected. This is a relatively uncommon form of anemia. About half of the cases are idiopathic and occur in younger adults secondary to an immune mediated destruction of hematopoietic progenitor cells by cytotoxic T cells. The other half are associated with a chemical agent, radiation, or drugs (antibiotics, anticonvulsants, anti-inflammatory drugs). Fanconis anemia is a rare, familial form of aplastic anemia associated with bone abnormalities, microcephaly, hypogenitalism, renal or splenic hypoplasia, mental retardation, and hyperpigmentation of the skin.

Associated laboratory abnormalities include a normocytic to macrocytic anemia, leukopenia, thrombocytopenia, and a low reticulocyte index. The bone marrow is hypocellular. Therefore, diagnosis is made via bone marrow biopsy that shows decreased cellularity (less than 25% of normal), increased marrow fat, and a lack of malignant cells or marrow fibrosis. If difficulty is encountered in obtaining a bone marrow aspirate, a different diagnosis such as hairy cell leukemia should be considered. The serum iron is usually elevated.

Symptoms are secondary to the associated anemia, thrombocytopenia, and leukopenia. Weakness, fatigue, and lethargy are a direct result of the anemia. Neutropenia results in an increased susceptibility to bacterial and fungal infections, especially in the mouth and perirectal area. Petechiae, ecchymosis, and epistaxis are the result of thrombocytopenia. Female patients often experience menorrhagia. Physical examination should reveal a lack of lymphadenopathy, splenomegaly, or hepatomegaly. 

When available, bone marrow transplantation from an HLA-compatible person is a therapeutic option. If transplant is planned, transfusions should be kept to a minimum as they represent a risk to successful transplantation. Transfusions should be given if necessary with surveillance of the serum ferritin level to monitor for iron overload. Platelet transfusions are necessary for uncontrollable bleeding episodes. Protective isolation and prophylaxis for opportunistic infections with gram-negative bacteria or fungi is prudent in cases of severe neutropenia. Equine antithymocyte globulin (ATG) at a dosage of 15 mg/kg diluted in 500 ml of normal saline infused over 6 hours for 5 consecutive days is a viable treatment option in older patients or in patients with a compatible donor for transplantation in anticipation of the procedure. Prednisone 40 mg/m2/day beginning on the seventh day of therapy and continuing for 10 days is given when allergic reactions or serum sickness occur.