Stem cell failure may involve either the pluripotential
stem cell or the erythroid committed stem cell.
Aplastic anemia is the failure of pluripotential stem cells
to produce red cells, white cells, and megakaryocytes. In aplastic anemia,
the CD 34 cell population (hematopoietic stem cells and progenitors)
is deficient in number.
If only the progenitor cell of the BFU-E is affected the disorder is
known as pure red cell aplasia.
Stem cells may be damaged by radiation, infection, drugs, chemicals,
and immune mechanisms. Cytokines inhibiting hematopoiesis (IFN-gamma;
TNF from T cells) may suppress hematopoiesis resulting in an aplastic
The cause of stem cell failure is often unknown. You should be familiar
with the following causes:
-parvovirus; hepatitis (non-A, non-B); EBV
-marrow suppressive chemotheraputic agents -alkylating agents;
-chloramphenicol; quinacrine; phenylbutazone;
-benzene; weed killers/insecticides; arsenic
Hematopoietic cells are particularly sensitive to high energy (gamma;
X-ray) radiation. Total-body irradiation of 300-500 Grays can cause
complete hematopoietic failure as occurred with the Chernoble disaster.
Severe, but limited (4-6 weeks) anemia, leukopenia, and thrombocytopenia
can result from sublethal radiation. Long term low energy radiation
(alpha and beta particles) may damage hematopoietic cells if ingested.
Radium watch dial painters in Waterbury, CT ingested radium by pointing
their brushes on their lips.
Aplasia usually presents with pancytopenia - decreased
numbers of erythrocytes, leukocytes, and platelets in the peripheral
Aplasia must be confirmed by bone marrow biopsy. Other hematopoietic
disorders can present with pancytopenia and must be distinguished from
aplastic anemia. These include paroxysmal nocturnal hemoglobinuria,
myelodysplasia, and acute leukemia.
Note that hypersplenism can cause a pancytopenia, but that the marrow
would be hyperplastic, rather than hypocellular as in aplasia.
Patients with aplastic anemia suffer from anemia, hemorrhage, and
The degree of severity is judged by several factors including:
-marrow cellularity < 25%
- absolute recticulocyte count < 40,000/mml
-platelets < 20,000/mml
-granulocyte count < 500/ml (some use < 200/mml)
In severe aplastic anemia the 1-year survival is approximately 30%.
A few instances of spontaneous recovery are reported. With mild-moderate
disease survival may be as high as 80% at one year.
In the early stages of aplastic anemia, the first line
of therapy is to attempt to stimulate the marrow by giving the patient
erythropoietin and GM-CSF. Others favor a combination of antithymocyte
globulin, high-dose corticosteroids, and cyclosporine as the therapy
of choice although bone marrow transplant is an option to reestablish
In the early stages of aplastic anemia the first line of therapy
is to attempt to stimulate the marrow by giving the patient erythropoietin
If this fails thymocyte gamma globulin and/or androgen therapy may
Others favor a combination of antithymocyte globulin, high-dose corticosteroids,
and cyclosporine as the therapy of choice.