Aplastic anemia is a disorder of the hematopoietic stem cell that results in a loss of blood cell precursors, hypoplasia or aplasia of bone marrow, and cytopenias in two or more cell lines (red blood cells, white blood cells, and/or platelets). Symptoms result from anemia, thrombocytopenia (petechiae, bleeding), or leukopenia (infections). Diagnosis requires demonstration of peripheral pancytopenia and a bone marrow biopsy revealing a hypocellular marrow. Treatment usually involves immunosuppression with equine antithymocyte globulin and cyclosporine, or bone marrow transplantation.
(See also Overview of Decreased Erythropoiesis.)
The term aplastic anemia commonly implies a panhypoplasia of the marrow with cytopenias in at least two hematopoietic lineages. In contrast, pure red blood cell (RBC) aplasia is restricted to the erythroid cell line.
Etiology of 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)
- Drugs (eg, antineoplastic drugs, antibiotics, nonsteroidal anti-inflammatory drugs, antiseizure drugs, acetazolamide, gold salts, penicillamine, quinacrine)
- Viruses (Epstein-Barr virus and cytomegalovirus)
- Hepatitis (seronegative for hepatitis viruses)
The precise mechanism remains unclear but in the majority of cases involves an immune attack on the hematopoietic stem cell. Clonal hematopoiesis is frequently present, and there is a risk of progression to myeloid malignancy.
Symptoms and Signs of Aplastic Anemia
The onset of aplastic anemia usually is insidious, often occurring over weeks or months after exposure to a toxin, 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.
Diagnosis of Aplastic Anemia
- Complete blood count (CBC) and reticulocyte count
- Bone marrow examination
Aplastic anemia is suspected in patients, particularly young patients, with pancytopenia. Severe aplastic anemia is defined by a bone marrow with < 30% 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)
Treatment of Aplastic Anemia
- Hematopoietic stem cell transplantation
- If transplantation is not an option, immunosuppression with equine antithymocyte globulin and cyclosporine
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. Because transfusions pose a risk to subsequent transplantation, blood products are used only when essential.
In those patients unfit for transplant or lacking a donor, immunosuppressive treatment with equine antithymocyte globulin (ATG) combined with cyclosporine produces overall response rates of approximately 60 to 80%. Allergic reactions and serum sickness may occur. In refractory cases, thrombopoietin agonists have shown some efficacy in clinical trials, as have haploidentical bone marrow transplants (1, 2).
- 1. DeZern AE, Zahurak M, Symons H, et al: Alternative donor transplantation with high-dose post-transplantation cyclophosphamide for refractory severe aplastic anemia. Biol Blood Marrow Transplant 23(3):498–504, 2017. doi: 10.1016/j.bbmt.2016.12.628
- 2. Winkler T, Fan X, Cooper J, et al: Treatment optimization and genomic outcomes in refractory severe aplastic anemia treated with eltrombopag. Blood 133(24):2575–2585, 2019. doi: 10.1182/blood.2019000478
Key Points about Aplastic Anemia
- Aplastic anemia involves panhypoplasia of the marrow with anemia, leukopenia, and thrombocytopenia.
- Many cases are idiopathic, but chemicals, drugs, or radiation may be causes.
- Bone marrow examination shows a variable degree of hypocellularity.
- Treatment is with stem cell transplant or immunosuppression with equine antithymocyte globulin and cyclosporine.
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