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Aplastic Anemia

A. Idiopathic

B. Constitutional (congenital Fanconi's aplastic anemia)

C. Chemical & physical agents

  1. Dose related: chloramphenicol, benzene, ionizing radiation, alkylating agents, antimetabolites, mitotic inhibitors, anthracyclines, inorganic arsenical
  2. Idiosyncratic: chloramphenicol, phenylbutazone, sulfa drugs, gold compounds, organic arsenical, insecticides, hydantoin

D. Hepatitis

E. Immunologically mediated aplasia

F. Pregnancy

G. Paraxymal nocturnal hemoglobinuria

H. Misc: SLE, pancreatitis, miliary TB, viral infections, Simmond's disease.

Grand Round: Acquired Aplastic Anemia  (NEJM July 21, 1999;282:   - Neal S. Young, MD )


REF:  ACP  PIER 2002

Differential Diagnosis of Severe Aplastic Anemia




Pancytopenia and hypocellular marrow due to hypoplastic MDS Hypocellular marrow mimics severe AA, but subtle dysplastic morphologic features and abnormal cytogenetics may help distinguish between hypoplastic MDS and severe AA The most useful test is cytogenetics of bone marrow. However, normal cytogenetics may be seen in both MDS and severe AA. If abnormal, a diagnosis of MDS is favored
Pancytopenia and hypocellular marrow due to paroxysmal nocturnal hemoglobinuria History of hemolytic anemia with dark urine. Positive PNH test distinguishes from severe AA Flow cytometry is most useful test for detecting the presence or absence of PNH. Positive urine hemosiderin in Ham or sucrose lysis test support diagnosis of PNH  
Pancytopenia and hypocellular marrow due to FA or dyskeratosis congenita Presentation in childhood. Characteristic physical abnormalities, particularly bony abnormalities (Fanconi) and skin disease (dyskeratosis congenita). Abnormal cytogenetics tests showing chromosome fragility characteristic of FA   Patients with FA may evolve into severe AA. Therefore, all patients under age 40 with severe AA should have chromosome fragility testing done to exclude FA as cause of severe AA  
Pancytopenia due to severe megaloblastic anemia Deficiencies of vitamin B12 or folic acid may result in severe pancytopenia. Bone marrow aspiration and biopsy result show cellular marrow   Normal B12, folate, and cellular bone marrow aspirate and biopsy result differentiates from severe AA  
Pancytopenia due to myelophthisic (marrow invasive) condition The bone marrow biopsy shows cellular marrow with malignant cells, including acute myelogenous and lymphoblastic leukemia, myelodysplastic syndrome, Hodgkin disease, non-Hodgkin lymphoma, and multiple myeloma. Occasionally, metastatic solid tumors for breast, lung, or other cancers may cause pancytopenia excluding diagnosis of severe AA. Physical exam may show hepatosplenomegaly or lymphadenopathy, which is rare in severe AA   Invasion of bone marrow by any solid tumor or by any hematologic malignancy may result in pancytopenia. Review of blood smear and bone marrow aspirate and biopsy result excludes severe AA. Blood smear may show teardrops, nucleated erythrocytes, and immature cells consistent with marrow-invasive tumor or leukemia, lymphoma, or chronic inflammatory disease  
Pancytopenia due to chronic bacterial or viral infections Positive serologic test results for viruses and evidence of hepatitis with elevated liver function test (AST, ALT) results suggesting chronic viral infection from hepatitis B, C, infectious mononucleus, cytomegalovirus, or parvovirus. Bone marrow aspirate and biopsy result show cellular marrow   Chronic viral diseases, granulomatous diseases (tuberculosis), or, rarely, bacterial infections may cause pancytopenia with cellular marrow or may evolve into true aplastic anemia  
Pancytopenia due to hypersplenism Blood counts are not usually severely depressed. Spleen is enlarged. Frequent hepatomegaly. Cellular marrow on biopsy Liver disease commonly associated with hypersplenism
Autoimmune pancytopenia Patients with severe pancytopenia with maturation arrest due to antiprogenitor cell or stem cell antibodies; bone marrow aspirate is usually cellular   Rare condition caused by anti-stem cell antibodies distinguishable by presence of cellular marrow on biopsy and evidence of maturation arrest in all three lineages (12)  

AA = aplastic anemia; ALT = alanine aminotransferase; AST = aspartate aminotransferase; FA = Fanconi anemia; MDS = myelodysplastic syndrome; PNH = paroxysmal nocturnal hemoglobinuria.

Non-drug Therapy    

Consider one of several non-drug therapies for the treatment of severe AA, depending on the individual clinical situation.

Drug Therapy    

Use immunosuppressive therapy as the treatment of choice for patients with severe AA who are not candidates for allogeneic bone marrow transplantation.

Drug Treatment for Severe Aplastic Anemia



High-dose cyclophosphamide

Androgens oxymetholone (Anadrol-50)

High dose methylprednisolone

Hematopoietic growth factors (G-CSF, GM-CSF)

Mycophenolate mofetil (CellCept)

*AA = aplastic anemia; ALG = antilymphocyte globulin; ATG = antithymocyte globulin; bid = twice daily;
G-CSF = granulocyte colony-stimulating factor; GM-CSF = granulocyte-macrophage colony-stimulating factor; iv = intravenous; po = oral;
PNH = paroxysmal nocturnal hemoglobinuria; qod = every other day; qd = once daily.