The over-expression of Epo may be associated with certain pathophysiological conditions (1,
2). Polycythemia exists when there is an overproduction of red blood cells (RBCs). Primary
polycythemias, such as polycythemia vera, are caused by Epo-independent growth of
erythrocytic progenitors from abnormal stem cells and low to normal levels of Epo are found in
the serum of affected patients. On the other hand, various types of secondary polycythemias
are associated with the production of higher than normal levels of Epo. The overproduction of
Epo may be an adaptive response associated with conditions that produce tissue hypoxia, such
as living at high altitude, chronic obstructive pulmonary disease, cyanotic heart disease, sleep
apnea, high-affinity hemoglobinopathy, smoking, or localized renal hypoxia (1, 2). In other
instances, excessive Epo levels are the result of production by neoplastic cells. Cases of
increased Epo production and erythrocytosis have been reported for patients with renal
carcinomas (3), benign renal tumors (4), Wilms' tumors, hepatomas (5), liver carcinomas (6),
cerebellar hemangioblastomas (3, 7, 8), adrenal gland tumors (9), smooth muscle tumors (3, 9),
and leiomyomas (10).
Deficient Epo production is found in conjunction with certain forms of anemias. These include
anemia of renal failure and end-stage renal disease (1, 2, 11), anemias of chronic disorders
[chronic infections (1), autoimmune diseases (1), rheumatoid arthritis (12), AIDS (13),
malignancies (14)], anemia of prematurity (2), anemia of hypothyroidism (2), and anemia of
malnutrition (2). Many of these conditions are associated with the generation of IL-1 and TNF-alpha,
factors that have been shown to be inhibitors of Epo activity (1, 15). Other forms of anemias, on
the other hand, are due to Epo-independent causes and affected individuals show elevated
levels of Epo (2). These forms include aplastic anemias, iron deficiency anemias, thalassemias,
megaloblastic anemias, pure red cell aplasias, and myelodysplastic syndromes.
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