Aplastic anemia is a severe hematological syndrome characterized by peripheral pancytopenia associated with bone marrow hypocellularity. It results from a quantitative or qualitative impairment of hematopoietic stem cells, leading to decreased production of red blood cells, white blood cells, and platelets. Clinically, it presents as normocytic normochromic anemia with low reticulocyte count, along with signs of leukopenia and thrombocytopenia. If untreated, it carries a high risk of severe infections, hemorrhage, and death, although recent therapeutic advances have significantly improved the prognosis.
Aplastic anemia may be idiopathic (no identifiable cause, about 70% of cases) or secondary to environmental, pharmacologic, or infectious factors.
Secondary forms are associated with exposure to myelotoxic agents such as benzene, ionizing radiation, drugs like chloramphenicol and carbamazepine, or viral infections including Epstein-Barr virus, non-A-B-C hepatitis, and HIV. Rare genetic causes include disorders such as Fanconi anemia and dyskeratosis congenita.
The pathogenesis is predominantly immune-mediated: activated cytotoxic T lymphocytes target normal hematopoietic stem cells, inducing apoptosis through the release of interferon-gamma and TNF-alpha. This aberrant immune response leads to progressive stem cell depletion and a reduction in all hematopoietic lineages.
Bone marrow biopsy typically reveals hypocellularity replaced largely by adipose tissue, with no evidence of neoplastic infiltration or significant fibrosis. This histological finding helps distinguish it from other causes of pancytopenia, such as acute leukemias or myelodysplastic syndromes (see myelodysplastic anemia).
Clinical severity is determined by the rate and extent of marrow destruction: in severe cases, the depletion may prevent any spontaneous hematopoietic recovery.
The clinical presentation ranges from mild, incidental findings to rapidly progressive bone marrow failure.
History and physical examination should investigate environmental exposures, medication history, recent infections, autoimmune conditions, and family history of hematologic disorders.
The main symptoms relate to deficiencies in all three cell lines:
On physical examination, signs of anemia and bleeding tendency may be observed. The absence of splenomegaly or lymphadenopathy helps differentiate aplastic anemia from leukemias or infiltrative disorders.
The diagnosis relies on identifying peripheral pancytopenia with hypocellular bone marrow, in the absence of malignant infiltration or fibrosis.
The diagnostic workup includes:
Additional tests are used to exclude alternative diagnoses or associated conditions:
Treatment choice depends on age, severity of pancytopenia, and availability of an HLA-compatible donor.
In young patients with a suitable donor, allogeneic hematopoietic stem cell transplantation is the treatment of choice, offering a curative option with 5-year survival rates exceeding 70–80%.
For patients not eligible for transplant, immunosuppressive therapy with antithymocyte globulin (ATG) and cyclosporine A is standard of care, with response rates of 60–70%.
Supportive care includes transfusions, antimicrobial prophylaxis, and the use of hematopoietic stimulants such as eltrombopag, which are essential in the management of critical phases.
Prognosis has significantly improved thanks to therapeutic advances, but risks remain for relapse, clonal evolution to MDS or acute leukemia, and emergence of PNH clones.
Complications arise primarily from pancytopenia and the use of immunosuppressive agents:
Regular hematologic follow-up is essential for early detection and management of these complications.