Aplastic Anemia

Chapter: Aplastic Anemia
McMaster Section Editor(s): Mark Crowther
Section Editor(s) in Interna Szczeklika: Andrzej Hellmann, Bogdan Ochrem
McMaster Author(s): Mark Crowther
Author(s) in Interna Szczeklika: Maria Podolak-Dawidziak
Additional Information

See also: Anemia: General Considerations.

Definition, Etiology, PathogenesisTop

Aplastic anemia (AA) is bone marrow hypoplasia or aplasia causing pancytopenia.

The primary cause of AA is either an inherited anomaly or acquired injury of hematopoietic stem cells or the bone marrow microenvironment, which leads to the inhibition of cellular proliferation and differentiation.

Classification of AA:

1) Inherited AA (20% of cases): Fanconi anemia.

2) Acquired AA (80% of cases): Idiopathic (>70% of cases), prior acute hepatitis (5%-10%), physical factors (radiation), chemicals (benzene and other organic solvents, trinitrotoluene, pesticides, herbicides), drugs (busulfan, cyclophosphamide, anthracyclines, nitrosoureas, phenylbutazone, methotrexate, chloramphenicol, sulfonamides, gold compounds, chloroquine, chlorpropamide, phenytoin, allopurinol, thiazides), viral infections (retroviruses, hepatitis A virus, hepatitis B virus, hepatitis C virus, HIV, Epstein-Barr virus, herpesviruses, parvovirus B19, dengue virus), systemic connective tissue diseases, thymoma, other blood diseases (paroxysmal nocturnal hemoglobinuria [PNH], myelodysplastic syndrome [MDS], aplastic crisis in the course of various types of hemolytic anemia), and pregnancy (very rare).

Clinical Features Top

Symptoms of AA may develop rapidly (within several days) or slowly (several weeks or months). Clinical manifestations of AA result from anemia, neutropenia, and thrombocytopenia.


Diagnostic Tests

1. Complete blood count: Normocytic (sometimes macrocytic) and normochromic anemia, very low reticulocyte counts (<10,000/microL), leukopenia with neutropenia (usually <1500/microL), thrombocytopenia (<10,000/microL in patients with severe disease).

2. Bone marrow examination: The aspirate usually reveals decreased numbers of hematopoietic cells (<30%), a proportion of fat cells to hematopoietic cells >3, and no malignant cells; trephine biopsy specimens reveal few cellular fields in a generally hypocellular marrow.

3. Other studies: Flow cytometry to detect a PNH clone, cytogenetic studies, cobalamin and folate levels, virology, liver function tests, antinuclear antibodies and anti-dsDNA antibodies, chest radiographs, abdominal ultrasonography.

Diagnostic Criteria

Peripheral blood cytopenia (affecting ≥2 of the 3 lineages) and hypocellular bone marrow, after other causes have been excluded (see below). The diagnosis of severe AA is confirmed if ≥1 of the following 3 criteria are fulfilled:

1) Neutrophil count <500/microL.

2) Platelet count <20,000/microL.

3) Reticulocyte count <20,000/microL.

Differential Diagnosis

Acute leukemia (particularly acute lymphoblastic leukemia), hairy cell leukemia, MDS, severe megaloblastic anemia, PNH, hypersplenism, bone marrow infiltrates (cancer, amyloidosis), lymphomas.


1. General measures:

1) Promptly refer patients with severe AA to a hematology center.

2) Transfuse leukoreduced packed red blood cells (PRBCs) and platelets only when this is considered essential. Hematopoietic stem cell transplantation (HSCT) may be compromised by a prior transfusion therapy.

3) Consider prophylactic antibacterial and antifungal treatment (this is usually necessary in patients with neutropenia <200/microL), granulocyte colony-stimulating factor (G-CSF) (see Immunodeficiency Disorders) (in patients with severe infections, particularly caused by antibiotic- and/or antifungal-resistant pathogens), and antiviral prophylaxis.

4) Treat the probable underlying condition(s).

2. Allogeneic HSCT is the treatment of choice for otherwise eligible patients <40 years with severe AA for whom a related donor is available. Allogeneic HSCT is curative in 60% to 90% of patients. In case of no response to a 6-month immunosuppressive treatment, allogeneic HSCT should be considered. Related donors are generally preferred to unrelated donors

3. Immunosuppressive treatment is indicated in patients who are not planned for allogeneic HSCT and results in improvement in 60% to 80% of cases. Use antithymocyte globulin (ATG) combined with glucocorticoids and cyclosporine (INN ciclosporin). In patients treated with ATG, all the transfused PRBCs and platelet concentrates must be irradiated.

4. Androgens (eg, oxymetholone 2.5 mg/kg/d) may be effective in Fanconi anemia and acquired AA with refractoriness or contraindications to immunosuppressive treatment; however, they should be discontinued if no improvement is achieved within 4 to 6 months. In patients with good response to treatment, the dose is tapered down slowly to discontinuation.

5. Alemtuzumab: In patients with recurrent AA, the drug has an efficacy similar to ATG combined with cyclosporine.


In patients with severe AA who have not been treated with allogeneic HSCT, 2-year mortality rates are 80%. The most frequent causes of death are severe bacterial or fungal infections. AA may transform to MDS, acute leukemia, or PNH.

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