Chapter 102. Aplastic Anemia, Myelodysplasia, and Related Bone Marrow Failure Syndromes (Part 7)

Bone Marrow The bone marrow is usually readily aspirated but dilute on smear, and the fatty biopsy specimen may be grossly pale on withdrawal; a "dry tap" instead suggests fibrosis or myelophthisis.
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Chapter 102. Aplastic Anemia, Myelodysplasia, and Related Bone Marrow Failure Syndromes (Part 7) Chapter 102. Aplastic Anemia, Myelodysplasia, and Related Bone Marrow Failure Syndromes (Part 7) Bone Marrow The bone marrow is usually readily aspirated but dilute on smear, and thefatty biopsy specimen may be grossly pale on withdrawal; a dry tap insteadsuggests fibrosis or myelophthisis. In severe aplasia the smear of the aspiratedspecimen shows only red cells, residual lymphocytes, and stromal cells; the biopsy(which should be >1 cm in length) is superior for determination of cellularity andshows mainly fat under the microscope, with hematopoietic cells occupying for mildly megaloblastic erythropoiesis; megakaryocytes are invariably greatlyreduced and usually absent. Areas adjacent to the spicule should be searched formyeloblasts. Granulomas (in cellular specimens) may indicate an infectiousetiology of the marrow failure. Ancillary Studies Chromosome breakage studies of peripheral blood using diepoxybutane ormitomycin C should be performed on children and younger adults to excludeFanconis anemia. Genetic analysis applicable to the constitutional marrow failurestates is available in some laboratories. Chromosome studies of bone marrow cellsare often revealing in MDS and should be negative in typical aplastic anemia.Flow cytometric assays have replaced the Ham test for the diagnosis of PNH.Serologic studies may show evidence of viral infection, such as Epstein-Barr virusand HIV. Posthepatitis aplastic anemia is typically seronegative. The spleen sizeshould be determined by CT scanning or ultrasound if the physical examination ofthe abdomen is unsatisfactory. MRI may be helpful to assess the fat content of afew vertebrae in order to distinguish aplasia from MDS. Diagnosis The diagnosis of aplastic anemia is usually straightforward, based on thecombination of pancytopenia with a fatty, empty bone marrow. Aplastic anemia isa disease of the young and should be a leading diagnosis in the pancytopenicadolescent or young adult. When pancytopenia is secondary, the primary diagnosisis usually obvious from either history or physical examination: the massive spleenof alcoholic cirrhosis, the history of metastatic cancer or systemic lupuserythematosus, or miliary tuberculosis on chest radiograph (Table 102-1). Diagnostic problems can occur with atypical presentations and amongrelated hematologic diseases. While pancytopenia is most common, some patientswith bone marrow hypocellularity have depression of only one or two of threeblood lines, sometimes showing later progression to more recognizable aplasticanemia. The bone marrow in constitutional aplastic anemia is indistinguishablemorphologically from the aspirate in acquired disease. The diagnosis can besuggested by family history, abnormal blood counts since childhood, or thepresence of associated physical anomalies. Aplastic anemia may be difficult todistinguish from the hypocellular variety of MDS: MDS is favored by findingmorphologic abnormalities, particularly of megakaryocytes and myeloid precursorcells, and typical cytogenetic abnormalities (see below). Prognosis The natural history of severe aplastic anemia is rapid deterioration anddeath. Provision first of red blood cell and later of platelet transfusions andeffective antibiotics are of some benefit, but few patients show spontaneousrecovery. The major prognostic determinant is the blood count; severe disease isdefined by the presence of two of three parameters: absolute neutrophil count