Chapter 62: Aplastic Anemia

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

Epidemiology

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

Work-up