Description

• Pancytopenia due to hypocellular bone marrow without the presence of infiltrates or fibrosis; classified as acquired (much more common) and congenital
• Acquired aplastic anemia: insidious onset; due to exogenous insult triggering an autoimmune reaction; often responsive to immunosuppression
• Congenital forms: rare, mostly present in childhood (exception is atypical presentation of Fanconi syndrome in adults; 30s for males and 40s for females)
• The occurrence of specific mutations in genes of the telomere complex in acquired aplastic anemia has blurred the distinction between the congenital and acquired forms.
• System(s) affected: heme/lymphatic/immunologic
• Synonym(s): hypoplastic anemia; panmyelophthisis; refractory anemia; aleukia hemorrhagica; toxic paralytic anemia

Geriatric Considerations
The elderly are often exposed to large numbers of drugs and therefore may be more susceptible to acquired aplastic anemia.

Pediatric Considerations

• Congenital forms of aplastic anemia require different treatment regimens than acquired forms.
• Acquired aplastic anemia is seen in children exposed to ionizing radiation or treated with cytotoxic chemotherapeutic agents.

Pregnancy Considerations

• Pregnancy is a real but rare cause of aplastic anemia. Symptoms may resolve after delivery and with termination.
• Complications in pregnancy can occur from low platelet counts and paroxysmal nocturnal hemoglobinuria–associated aplastic anemia.

Epidemiology

• Predominant age: biphasic 15 to 25 years (more common) and >60 years
• Predominant sex: male = female

Incidence

• 2 to 3 new cases per million per year in Europe and North America
• The incidence is 3-fold higher in Thailand and China versus the Western world.

Etiology and Pathophysiology

• Idiopathic (~70% of the cases)
• Drugs: phenylbutazone, chloramphenicol, sulfonamides, gold, cytotoxic drugs, antiepileptics (felbamate, carbamazepine, valproic acid, phenytoin)
• Viral: HIV, Epstein-Barr virus (EBV), nontypeable postinfectious hepatitis (not A, B, or C), parvovirus B19 (mostly in the immunocompromised), atypical mycobacterium
• Toxic exposure (benzene, pesticides, arsenic)
• Radiation exposure
• Immune disorders (systemic lupus erythematosus, eosinophilic fasciitis, graft versus host disease)
• Pregnancy (rare)
• Congenital (Fanconi anemia, dyskeratosis congenita, Shwachman-Diamond syndrome, amegakaryocytic thrombocytopenia)
• The immune hypothesis: activation of T cells with associated cytokine production leading to destruction or injury of hematopoietic stem cells. This leads to a hypocellular bone marrow without marrow fibrosis.
• The activation of T cells likely occurs because of both genetic and environmental factors. Exposure to specific environmental precipitants, diverse host, genetic risk factors, and individual differences in characteristics of immune response likely account for variations in its clinical manifestations and patterns of responsiveness to treatment.
• Telomerase deficiency leads to short telomeres. This leads to impaired regenerative capacity and hence a reduction in marrow progenitors and qualitative deficiency in the repair capacity of hematopoietic tissue.
• Reduction of natural killer cells in the bone marrow
• A somatic mutation of the PIGA gene underlies the clonal disease paroxysmal nocturnal hemoglobinuria: There is direct evidence that the expansion of the PIGA mutant clone results from Darwinian selection exerted by a glycosylphosphatidylinositol (GPI)-specific autoimmune attack (1).

Genetics

• Telomerase mutations found in a small number of patients with acquired and congenital forms. These mutations render carriers more susceptible to environmental insults.
• Mutations in genes called TERC and TERT were found in pedigrees of adults with acquired aplastic anemia who lacked the physical abnormalities or a family history typical of inherited forms of bone marrow failure. These genes encode for the RNA component of telomerase.
• HLA-DR2 incidence in aplastic anemia is twice that in the normal population.

Risk Factors

• Treatment with high-dose radiation or chemotherapy
• Exposure to toxic chemicals
• Use of certain medications
• Certain blood diseases, autoimmune disorders, and serious infections
• Tumors of thymus (red cell aplasia)
• Pregnancy, rarely

General Prevention

• Avoid possible toxic industrial agents.
• Use safety measures when working with radiation.