Clinical Pearls & Morning Reports
Published October 13, 2021
Aplastic anemia is characterized by pancytopenia and the loss of hematopoietic stem cells, progenitor cells, and precursor cells in the bone marrow. Read the NEJM Case Records of the Massachusetts General Hospital here.
Q: What are some of the extrinsic causes of aplastic anemia?
A: Aplastic anemia results from one of three main mechanisms: damage by extrinsic factors, manifestations of familial genetic mutations, and autoimmune attack on hematopoietic stem cells and progenitor cells. Extrinsic causes of aplastic anemia are usually obvious and include major accidental or therapeutic exposure to radiation, chemotherapy, or massive exposure to benzene or pesticides such as organochlorines and organophosphates.
Q: Name the genetic disorder most commonly associated with aplastic anemia.
A: The genetic disorder most commonly associated with aplastic anemia is Fanconi’s anemia, a DNA repair defect that results from a mutation in 1 of at least 15 known genes. Patients with Fanconi’s anemia typically have bone marrow failure in the first or second decade of life, as well as other congenital abnormalities, including thumb and facial deformities and short stature. The second most common genetic cause of bone marrow failure is dyskeratosis congenita, which is due to mutations in genes involved in telomere repair or protection.
A: Up to 70% of cases of aplastic anemia occur sporadically, resulting from the sudden onset of T-cell–mediated destruction of hematopoietic stem cells and progenitor cells. Most cases of aplastic anemia are designated as idiopathic because the triggers for the immune attack on hematopoiesis are obscure. The most common known trigger for aplastic anemia is seronegative hepatitis, which precedes 5 to 10% of cases of aplastic anemia by approximately 2 to 3 months. The median age at the onset of hepatitis-associated aplastic anemia is 20 years. Aplastic anemia is also thought to occur after infection with common hepatitis viruses and other viruses, including HIV and parvovirus B19, but at a much lower frequency than with seronegative hepatitis.
A: Management of aplastic anemia depends on the severity of illness, the patient’s age, the availability of an appropriate stem-cell donor, and the presence of coexisting conditions that could limit the patient’s ability to undergo allogeneic stem-cell transplantation. The criteria for severe aplastic anemia are a bone marrow cellularity of less than 25% and at least two of the following features: an absolute neutrophil count in peripheral blood of less than 500 per microliter, a platelet count of less than 20,000 per microliter, or a reticulocyte count of less than 20,000 per microliter. Other than stem-cell transplantation, standard intensive approaches include combination immunosuppressive therapy. Although this approach is promising, rates of relapse and clonal evolution to myelodysplastic syndrome or acute myeloid leukemia are often higher in patients treated with immunosuppressive therapy alone than in those treated with stem-cell transplantation, with rates of failure-free survival beyond 10 years of less than 50% in some series. For this reason, the use of allogeneic stem-cell transplantation in medically fit patients with appropriate stem-cell donors has increased.