- Description
- Pancytopenia caused by bone marrow insufficiency
- Should not be confused with aplastic crisis, a condition in which erythropoiesis is temporarily suppressed (e.g., due to parvovirus B19 infection in patients with hemolytic anemias)
- Etiology
- Idiopathic in > 50% of cases
- Possibly immune-mediated
- May follow acute hepatitis (hepatitis-associated aplastic anemia)
- Medication side effects: carbamazepine, methimazole, NSAIDs, chloramphenicol, propylthiouracil, sulfa drugs, cytostatic drugs (esp. alkylating agents and antimetabolites)
- Dose-dependent reactions are caused by medications (eg, chemotherapy, immunosuppressives) that are toxic to the bone marrow when drug levels exceed a certain concentration for a certain period. They tend to be predictable in onset.
- Idiosyncratic reactions are often caused by antiseizure medications (eg, carbamazepine, valproic acid), sulfonamides, or nifedipine. They are unpredictable, unrelated to the dose of the drug, and may occur at any point during or after therapy. Although the mechanism is unclear, patients often have genetic mutations in drug-metabolizing enzymes or efflux pumps, which may promote toxicity.
- Toxins: benzene, cleaning solvents, insecticides, toluene
- Ionizing radiation
- Viruses: HBV, EBV, CMV, HIV
- Fanconi anemia
- Hereditary autosomal recessive disorder due to a DNA crosslink repair defect resulting in bone marrow failure
- Skeletal and organ abnormalities: short stature, hypo- and hyperpigmentation, cafe-au-lait spots, microcephaly, developmental delay, thumb and forearm malformations, kidney, GI, heart, eye, and ear abnormalities
- Laboratory tests show pancytopenia and normocytic or macrocytic anemia.
- ∼ 50% of patients with Fanconi anemia will develop acute myeloid leukemia or myelodysplastic syndromes in early adulthood.
- Pathophysiology
- Multipotent hematopoietic stem cells are destroyed by cytotoxic T cells or direct cytotoxic injury → bone marrow aplasia/hypoplasia → lack of circulating peripheral blood cells