Hematology / Oncology

Aplastic Anemia


Aplastic anemia (AA) is peripheral pancytopenia of all three blood cell lines and bone marrow aplasia caused by the absence or decline of hematopoietic stem cells.  As a result, the symptoms of aplastic anemia include those of anemia, but also the more concerning and potentially dangerous symptoms of leukocytopenia and thrombocytopenia, namely infection and bleeding.



AA has a triphasic incidence with peaks at 2-5 y/o (congenital cases), 20-25 y/o, and 55-60 y/p (the later typically due to acquired causes).



AA is most often the result of acquired direct destruction or previously well-functioning hematopoietic stem cells, though more rarely may also be caused by congenital disorders.


  • idiopathic
  • autoimmune disorders
  • Pregnancy: rare, self-limited cases of aplastic anemia in pregnancy that resolved with delivery have been reported
  • drugs: chloramphenicol (no longer in use in the United States, but apparently important for exams), gold, sulfonamides, anti-epileptic drugs (carbamazepine, felbamate, phenytoin, valproic acid), nifedipine, quinine, phenylbutazone (NSAID, now rarely used).
  • Toxins: benzene, possibly also solvents/degreasing agents, pesticides, industrial chemicals
  • ionizing radiation: exposure from radioactive materials, or radiation-producing devices.
  • infectious causes: aplastic anemia can occur in immunocompromised or sickle-cell patients infected with parvovirus B19 (a.k.a. erythema infectiosum, fifths disease) and more rarely with acute viral hepatitis or HIV


The four major congenital causes of AA may result in physical malformations in addition to the pancytopenia, though patients may not present with complete pancytopenia during the early disease stages.

  • Fanconi anemia: Autosomal recessive or X-linked familial condition with several genes implicated, causes pancytopenia, macrocytic anemia, congenital malformations, as well as propensity to malignancies (AML, MDS, Head & Neck SCC).
  • Dyskeratosis congenita: rare disorder with marrow failure, cancer predisposition (AML, solid tumors, especially SCC), and somatic abnormalities including short stature, pulmonary fibrosis, and ectodermal dysplasia (triad of reticulated hyperpigmented rash of face & trunk, nail dystrophy, and mucosal leukoplakia)
  • Shwachman-Diamond syndrome: usually presents in infancy with exocrine pancreatic dysfunction, bone marrow failure, and skeletal anomalies.
  • Amegakaryocytic thrombocytopenia: autosomal recessive disorder with isolated thrombocytopenia in infancy and absent/reduced megakaryocytes in bone marrow that presents typically as bleeding into skin, mucous membranes and GI tract, with development of pancytopenia around 4 years of age.


Symptoms and Signs

May reflect the decreased population of RBCs, WBCs or platelets, but lymphadenopathy or hepatosplenomegally are generally not present.

  • Anemia: pallor, fatigue, SOB.
  • Leukocytopenia: recurrent, typically bacterial infections, including pneumonia, UTI, and sepsis, as well as possible invasive fungal infections in immunocompromised patients.
  • thrombocytopenia: fever, petechiae, mucosal hemorrhage and/or ulceration, increased menstrual flow.


Differential Diagnosis

Differential for pancytopenia without splenomegaly includes AA, bone marrow failure (leukemia, myelodysplastic syndromes, bone marrow infiltration by tumor or fibrosis), paroxysmal nocturnal hemoglobinuria, severe megaloblastic anemia, and overwhelming infection by HIV



A careful review of family history for any cytopenias, congenital anomalies, cancer or infection predisposition, and exposure to toxins, drugs or radiation is important to try to distinguish between acquired or congenital AA.  Physical exam and history should include a careful history of medications and exposures, and special attention should be paid to physical features of specific inherited AA or other alternative causes of the pancytopenia, such as infections, rheum disorders or infections.

Diagnostic work-up: should consist of CBC, Bone marrow biopsy, testing for viral agents, serum folate and B12, CD 55/59 (red blood cell test for PNH), and chromosomal studies (Fanconi anemia, other inherited disorders).

  • CBC: pancytopenia and concurrent reduction in absolute number of reticulocytes, but no morphological abnormalities or abnormal cells should be present.
  • Bone Marrow: aspiration and biopsy of an undamaged site should show:
    • Profound hypocellularity and infiltration of marrow space with fat cells, lymphocytes, and marrow stroma
    • Residual hematopoietic cells may manifest dysplastic features such as multinucleated red cells, hyponucleated megakaryocytes, and hypolobulated and hypogranular myeloid cells.
    • No evidence of fibrosis, malignant or otherwise abnormal cells



Treatment course is dictated by the underlying etiology of the aplastic anemia.

Removal of the offending agent is appropriate if exposure to a toxic agent or drug is thought to be the underlying cause. 

Patients with acquired aplastic anemias tend to respond favorably to immunosuppressive therapy, e.g. antithymocyte globulin, cyclosporine, corticosteroids.

The only curative treatment option for patients in bone marrow failure is hematopoetic cell transplantation.  Outcomes are improved in younger patients (decreased incidence of complications related to the AA) with HLA-identical sibling donors or from autologous transplantation from stored cord-blood. 

Patients for whom transplant is not an option may also be considered for androgen therapy to alleviate the pancytopenia, though this treatment seems to be most effective at improving the anemia, then the thrombocytopenia, and last the neutropenia.

Hematopoetic growth factors such as granulocyte colony-stimulating factor or granulocyte-macrophage colony stimulating factor may be useful for raising the neutrophil count, but are less effective at treating the thrombocytopenia or anemia.



  1. Rosenthal, J, Woolfrey AE, Pawlowska A et al., Hematopoietic cell transplantation with autologous cord blood in patients with severe aplastic anemia: An opportunity to revisit the controversy regarding cord blood banking for private use. Pediatric Blood & Cancer 2011; 56(7), 1009-1012.
  2. Sanders, Jean E., et al. Late effects among pediatric patients followed for nearly 4 decades after transplantation for severe aplastic anemia. Blood 118.5 (2011): 1421-1428.
  3. Howard, Scott C., et al. Natural history of moderate aplastic anemia in children. Pediatric blood & cancer 43.5 (2004): 545-551.
  4. Young, Neal S., Phillip Scheinberg, and Rodrigo T. Calado. Aplastic anemia. Current opinion in hematology 15.3 (2008): 162.
  5. Young N, and Maciejewski G The Pathophysiology of Acquired Aplastic Anemia NEJM 1999;336:1365-72