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Aplastic Anemia

(Hypoplastic Anemia)


Gloria F. Gerber

, MD, Johns Hopkins School of Medicine, Division of Hematology

Reviewed/Revised Jun 2023
Topic Resources

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.

The term aplastic anemia commonly implies a panhypoplasia of the bone marrow with cytopenias in at least two hematopoietic lineages. In contrast, pure red blood cell (RBC) aplasia Pure Red Blood Cell Aplasia Acquired pure red blood cell aplasia is a disorder of erythroid precursors that results in an isolated normocytic anemia. White blood cells and platelets are not affected. Symptoms result from... read more 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

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.

Symptoms and Signs of Aplastic Anemia

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.

Diagnosis of Aplastic Anemia

  • 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

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).

Diagnosis reference

Treatment of Aplastic Anemia

  • Hematopoietic stem cell transplantation

  • If transplantation is not an option, immunosuppression with equine antithymocyte globulin and cyclosporine and sometimes eltrombopag

In aplastic anemia, hematopoietic stem cell transplantation Hematopoietic Stem Cell Transplantation Hematopoietic stem cell (HSC) transplantation is a rapidly evolving technique that offers a potential cure for hematologic cancers ( leukemias, lymphomas, myeloma) and other hematologic disorders... read more 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.

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. Long-term relapse or clonal evolution to myeloid malignancy occurs in up to half of patients.

Treatment references

  • 1. Peffault de Latour R, Kulasekararaj A, Iacobelli S, et al. Eltrombopag Added to Immunosuppression in Severe Aplastic Anemia. N Engl J Med 2022;386(1):11-23. doi:10.1056/NEJMoa2109965

  • 2. DeZern A, Zahurak ML, Symons HJ, et al. Alternative donor BMT with post-transplant cyclophosphamide as initial therapy for acquired severe aplastic anemia [published online ahead of print, 2023 Apr 21]. Blood 2023;blood.2023020435. doi:10.1182/blood.2023020435

  • 3. 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

  • Aplastic anemia involves panhypoplasia of the bone 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.

Drugs Mentioned In This Article

Drug Name Select Trade
Atgam, Thymoglobulin
Cequa, Gengraf , Neoral, Restasis, Sandimmune, SangCya, Verkazia
Diamox, Diamox Sequels
Cuprimine, Depen, D-PENAMINE
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