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Aplastic Anemia (AA)

Aplastic anemia is a distinct entity characterized by peripheral blood cytopenias and bone marrow hypocellularity. Aplastic anemia can be acquired or congenital. Acquired aplastic anemia is distinguished from iatrogenic marrow aplasia, the common occurrence of marrow hypocellularity after intensive cytotoxic chemotherapy



Incidence: 2 per 1 million of population per year (West) and 2- to 3-fold higher in Asia

Male-to-female ratio: 1:1


Incidence of aplastic anemia. In: Kaufman DW et al., eds. The drug etiology of agranulocytosis and aplastic anemia. New York, NY: Oxford University Press; 1991:159–169

Young NS et al. Blood 2006;108:2509–2519


Disease Severity

Severe aplastic anemia

  1. Bone marrow cellularity <25% of normal or 25–50% of normal with <30% residual hematopoietic cells, and

  2. Two out of 3 criteria: (a) neutrophils <500/mm3; (b) platelets <20,000/mm3; (c) reticulocytes <1%

Very severe aplastic anemia

  1. Bone marrow cellularity <25% of normal or 25–50% of normal with <30% residual hematopoietic cells, and

  2. (a) Neutrophil count <200/mm3 and (b) platelets <20,000/mm3 or reticulocytes <1%

Moderate (nonsevere) aplastic anemia

Patients who do not fulfill the above criteria


Bacigalupo A et al. Br J Haematol 1988;70:177–182

Bacigalupo A et al. Semin Hematol 2000;37:69–80

Camitta BM et al. Blood 1976;48:63–70

Rosenfeld S et al. JAMA 2003;289:1130–1135

Young NS et al. Biol Blood Marrow Transplant 2010;16(1 Suppl):S119–S125


Etiology and Classification

  1. Acquired aplastic anemia

    1. Idiopathic (2/3 of all cases)

    2. Secondary

      1. Drugs

        1. Predicted:

          • (1) Cytotoxic chemotherapeutic agents

            • Alkylating agents (busulfan, cyclophosphamide, melphalan)

            • Antimitotics (vincristine, vinblastine)

            • Antimetabolites (antifolate compounds, nucleotide analogs)

        2. Idiosyncratic:

          • (1) Chloramphenicol

          • (2) Antiprotozoal agents (quinacrine, chloroquine)

          • (3) Nonsteroidal antiinflammatory drugs: ibuprofen, indomethacin, sulindac, diclofenac, naproxen, phenylbutazone

          • (4) Anticonvulsants: hydantoins, carbamazepine, phenacemide, ethosuximide

          • (5) Gold and arsenic

          • (6) Sulfonamides

          • (7) Antithyroid drugs (methimazole, methylthiouracil, propylthiouracil)

          • (8) Oral hypoglycemic agents (tolbutamide, carbutamide, chlorpropamide)

          • (9) Penicillamine

          • (10) Mesalazine

      2. Chemicals: benzene, insecticides

      3. Radiation

      4. Viral infections:

        1. Parvovirus (rare, usually causes transient aplastic crisis, pure red cell aplasia)

        2. Hepatitis viruses (non-A, non-B, non-C hepatitis)

        3. Epstein-Barr virus

        4. Human immunodeficiency virus

      5. Immune disorders:

        1. Eosinophilic fasciitis

        2. Systemic lupus erythematosus

        3. Graft versus host disease, transfusion associated

        4. Hypoimmunoglobulinemia

        5. Thymoma and thymic carcinoma

      6. Paroxysmal nocturnal hemoglobinuria

      7. Pregnancy

  2. Inherited aplastic anemia

    1. Fanconi anemia

    2. Dyskeratosis congenita

    3. Shwachman-Diamond syndrome

    4. Amegakaryocytic thrombocytopenia


Young NS. In: Young NS, ed. Bone Marrow Failure Syndromes. 1st ed. Philadelphia, PA: WB Saunders; 2000:1–46



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It is important to exclude other disorders that may present with pancytopenia and a hypoplastic bone marrow

CBC with differential
  • All cell lineages may not be affected; bicytopenias or monocytopenias may occur

  • Decreased reticulocyte count

  • Red blood cells usually are normocytic but occasionally erythrocyte macrocytosis may be present

  • In the peripheral blood smear the remaining elements, while reduced, are morphologically normal

Bone marrow biopsy and aspiration
  • The degree of bone marrow hypocellularity may not correlate with the peripheral blood count

  • Marrow morphology is usually normal or may have erythroid megaloblastoid changes

  • The marrow space is composed of fat cells and marrow stroma

  • Malignant infiltrates or fibrosis are absent

Cytogenetic analysis of marrow cells
  • Usually normal in AA in contrast to MDS


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