Specimen:

Serum or Plasma

Collection Medium:

Alternate
Collection Media:

Plasma separator tube, Call laboratory for additional acceptable 
specimen collection containers.

Minimum:

Adult recommended minimum: 1.0 mL serum
Adult absolute minimum:    0.5 mL serum
Pediatric minimum:         0.4 mL serum

If additional tests are going to be ordered, extra red top tubes may be 
needed.  Please call the lab for consultation.

Rejection Criteria:

EDTA plasma specimens and hemolyzed specimens.

Delivery Instructions:

Deliver to laboratory immediately after collection.

Analytic Time:

4 working days

Reference Range:

Normal serum concentrations of erythropoietin for 95% of individuals 
with normal hematocrits range from 4-27 mU/mL.

As the hematocrit is lowered by iron deficiency, aplastic or hemolytic 
anemia, the concentration of erythropoietin increases as shown in the 
graph below. In the absence of anemia, elevated concentrations are seen 
in renal tumors, as a manifestation of renal transplant rejection, and 
in secondary polycythemia. Low values may be observed in 
hemochromatosis.

Decreased erythropoietin concentrations with an elevated hematocrit are 
observed in patients with polycythemia rubra vera, and with a decreased 
hematocrit in patients with HIV infection who are receiving AZT. 
Patients on AZT who have anemia and erythropoietin concentrations of 
less than or equal to 500 mU/mL, may benefit from therapy with 
recombinant EPO (NEJM 322:1488-1493, 1990).

EXPECTED ERYTHROPOIETIN CONCENTRATIONS IN PATIENTS WITH UNCOMPLICATED 
ANEMIA

          ERYTHROPOIETIN (mU/mL)

100,000|
       |
       |
       |
 10,000|.............
       |   .............
       |     .............
       |       .............
  1,000|        .............
       |           .............
       |             .............
       |               .............
    100|                .............
       |                   .............
       |                     .............
     10|                        .............
       |                           .............
       |______________________________________________
                10    20    30    40    50    60    70
                           (HEMATOCRIT %)

Source: Caro J and Erslev AJ. Erythropoietin assays and their use in 
the study of anemias. Contrib Nephrol 1988; 66:54-62. Review.

Test
Limitations:

Erythropoietin (EPO), a glycoprotein produced primarily by the kidney, 
is the factor regulating red blood cell (RBC) production in mammals. 
Renal production of EPO is regulated by changes in oxygen availability. 
Under conditions of hypoxia, the level of EPO in the circulation 
increases, leading to increased production of RBCs.

The overproduction of EPO may be associated with certain 
pathophysiological conditions. Polycythemia exists when there is an 
overproduction of RBCs. Primary polycythemias, such as polycythemia 
vera, are caused by EPO-independent growth of erythrocytic progenitors 
from abnormal stem cells. Low-to-normal levels of EPO are found in the 
serum of affected patients.

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. 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, benign renal 
tumors, Wilms' tumors, hepatomas, liver carcinomas, cerebellar 
hemangioblastomas, adrenal gland tumors, smooth muscle tumors, and 
leiomyomas.

Deficient levels of EPO production are found in conjunction with 
certain forms of anemias. These include anemia of renal failure and 
end-stage renal disease, anemias of chronic disorders, chronic 
infections, autoimmune diseases, rheumatoid arthritis, AIDS, 
malignancies, anemia of prematurity, anemia of hypothyroidism, and 
anemia of malnutrition. Many of these conditions are associated with 
the generation of interleukin 1 (IL-1) and tumor necrosis factor (TNF- 
alpha), factors that have been shown to be inhibitors of EPO activity. 
AIDS patients suffering from zidovudine-induced anemia have been 
reported to benefit from treatment with recombinant human 
erythropoietin if the baseline erythropoietin level is is less than or 
equal to 500 mU/mL.

Normal serum concentrations of erythropoietin for 95 percent of 
individuals with normal hematocrits range from 4-27 mU/mL. As the 
hematocrit is lowered by iron deficiency, aplastic, or hemolytic 
anemia, the concentration of erythropoietin increases as shown in the 
diagram above. In the absence of anemia, elevated concentrations are 
seen in renal tumors as a manifestation of renal transplant rejection 
and in secondary polycythemia. Low values may be observed in 
hemochromatosis.

Deceased erythropoietin concentrations with an elevated hematocrit are 
observed in patients with polycythemia rubra vera and with a decreased 
hematocrit in patients with HIV infection who are receiving AZT. 
Patients on AZT who have anemia and erythropoietin concentrations of 
less than or equal to 500 mU/mL may benefit from therapy with 
recombinant EPO.

Other forms of anemias are EPO-independent and affected individuals 
will show elevated levels of EPO. These include aplastic anemias, iron 
deficiency anemias, thalassemias, megaloblastic anemias, pure red-cell 
aplasias, and myelodysplastic syndromes.

Patients suffering from uncomplicated, EPO-independent anemia will have 
elevated concentrations of erythropoietin that are appropriate for the 
level of anemia. These values fall within the shaded area of the 
diagram above. Patients suffering from EPO-deficient anemias have 
erythropoietin levels that are inappropriately low for the degree of 
anemia. These values fall below the shaded area of the diagram above.

Methodology:

Chemiluminescent Immunoassay

CPT Code:

82668

See Additional Information:
Specimens Requiring Immediate Delivery