(See also Overview of Decreased Erythropoiesis Overview of Decreased Erythropoiesis Anemia, a decrease in the number of red blood cells (RBCs), hemoglobin (Hb) content, or hematocrit (Hct), can result from decreased RBC production (erythropoiesis), increased RBC destruction... read more .)
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
Chemicals (eg, benzene, inorganic arsenic)
Medications (eg, antineoplastic drugs, antibiotics, nonsteroidal anti-inflammatory drugs, antiseizure medications, acetazolamide, gold salts, penicillamine, quinacrine) or toxins
Hepatitis (seronegative for hepatitis viruses)
Viruses (Epstein-Barr virus and cytomegalovirus)
Inherited disorders of bone marrow failure due to genetic mutations (eg, Fanconi anemia Decreased red blood cell (RBC) production Anemia is a reduction in red cell mass or hemoglobin and is usually defined as hemoglobin or hematocrit > 2 standard deviations below the mean for age. Some authorities also consider a relative... read more , 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.
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.
In aplastic anemia, anemia may cause weakness and easy fatigability while severe thrombocytopenia Symptoms and Signs Platelets are circulating cell fragments that function in the clotting system. Thrombopoietin helps control the number of circulating platelets by stimulating the bone marrow to produce megakaryocytes... read more may cause petechiae, ecchymosis, and bleeding from the gums, into the conjunctivae, or other tissues. Agranulocytosis Neutropenia Neutropenia is a reduction in the blood neutrophil count. If it is severe, the risk and severity of bacterial and fungal infections increase. Focal symptoms of infection may be muted, but fever... read more 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 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 Diagnosis reference 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 ... read more ).
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).
1. DeZern AE, Symons HJ, Resar LS, Borowitz MJ, Armanios MY, Brodsky RA. Detection of paroxysmal nocturnal hemoglobinuria clones to exclude inherited bone marrow failure syndromes. Eur J Haematol 2014;92(6):467-470. doi:10.1111/ejh.12299
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.
Eltrombopag, a thrombopoietin receptor agonist, has shown potential efficacy in clinical trials in the upfront and refractory settings with immunosuppression, and haploidentical bone marrow transplants are promising to expand access to 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 (1, 2, 3 Treatment references 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 ... read more ).
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
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|
|Cequa, Gengraf , Neoral, Restasis, Sandimmune, SangCya, Verkazia|
|Diamox, Diamox Sequels|
|Cuprimine, Depen, D-PENAMINE|