Pathology

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 state.

The cause of stem cell failure is often unknown. You should be familiar with the following causes:

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 blood.

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 infection.

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 normal hematopoiesis.

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.

If this fails thymocyte gamma globulin and/or androgen therapy may be tried.

Others favor a combination of antithymocyte globulin, high-dose corticosteroids, and cyclosporine as the therapy of choice.