Aplastic Anemia

True aplastic anemia (most common in adolescents and young adults) is idiopathic in about half of cases. Recognized causes are

• Chemicals (eg, benzene, inorganic arsenic)

• Hepatitis (seronegative for hepatitis viruses)

• Pregnancy

• Radiation

• Viruses (Epstein-Barr virus and cytomegalovirus)

• Inherited disorders of bone marrow failure due to genetic mutations (eg, Fanconi anemia, Shwachman-Diamond syndrome, dyskeratosis congenita)

The precise mechanism remains unclear, but in the majority of acquired cases, the mechanism involves an immune attack on the hematopoietic stem cell. Clonal hematopoiesis is frequently present, and there is a risk of progression to a myeloid malignancy.

The onset of aplastic anemia usually is insidious, often occurring over weeks or months after exposure to a virus, medication or toxin (eg, insecticides, benzene), though occasionally it can be acute.

In aplastic anemia, anemia may cause weakness and easy fatigability while severe thrombocytopenia may cause petechiae, ecchymosis, and bleeding from the gums, into the conjunctivae, or other tissues. Agranulocytosis commonly causes life-threatening infections. Splenomegaly is absent unless induced by transfusion hemosiderosis.

Petechiae in Immune Thrombocytopenia (ITP)

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By permission of the publisher. From Deitcher S. In Atlas of Clinical Hematology. Edited by JO Armitage. Philadelphia, Current Medicine, 2004.

Ecchymoses in Immune Thrombocytopenia

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By permission of the publisher. From Deitcher S. In Atlas of Clinical Hematology. Edited by JO Armitage. Philadelphia, Current Medicine, 2004.

• Complete blood count (CBC) and reticulocyte count

• Bone marrow examination with cytogenetic and molecular testing

• Flow cytometry for paroxysmal nocturnal hemoglobinuria (PNH) clone

• Consideration of genetic testing especially in young patients or those with suggestive family history or characteristic dysmorphia

Detection of a PNH clone can exclude an inherited syndrome (1).

Aplastic anemia is suspected in patients, particularly young patients, with pancytopenia. Severe aplastic anemia is defined by a bone marrow with < 25% cellularity (hypocellularity) and the presence of ≥ 2 of the following:

• Absolute neutrophil count < 500/microL (< 0.5 × 10⁹/L)

• Absolute reticulocyte count < 60,000/microL (< 60 × 10⁹/L)

• Platelet count < 20,000/microL (< 20 × 10⁹/L)

Very severe aplastic anemia is defined as absolute neutrophil count < 200/microL (< 0.2 x 10⁹/L).

• Hematopoietic stem cell transplantation

In aplastic anemia, hematopoietic stem cell transplantation can be curative and is the treatment of choice, particularly in younger patients with a matched donor. At diagnosis, siblings are evaluated for HLA (human leukocyte antigen) compatibility.

hematopoietic stem cell transplantation (1, 2, 3).