A patient who does not respond to erythropoietin as expected should be evaluated for a possible explanation.


Indications for evaluation:

(1) fails to respond

(2) unable to maintain hemoglobin levels after an initial response

(3) higher than expected doses required


Mechanisms associated with failure to respond to erythropoietin:

(1) nutritional

(2) blood loss

(3) erythroid production failure

(4) toxic

(5) infection

(6) endocrine disorders

(7) an occult infection or inflammatory condition (which may result in hemolysis, failure of red blood cell production or blood loss)


NOTE: Rare patients treated with recombinant erythropoietin may develop red cell aplasia, which is discussed later in another section.


Nutritional causes:

(1) iron deficiency

(2) folic acid and/or vitamin B12 deficiency



• Iron deficiency is common in candidates for erythropoietin and may be absolute (low body iron stores) or functional (unable to mobilize iron stores). The transferrin saturation should be >= 20% and the serum ferritin should be >= 100 ng/mL.


Blood loss:

(1) hemolysis

(2) occult blood loss


Failure in red blood cell production:

(1) thalassemia or sickle cell disease (hemoglobinopathy)

(2) myelodysplasia

(3) myelotoxic effect therapy

(4) progression in underlying malignancy



(1) aluminum toxicity (in patients with renal failure)


Endocrine disorders:

(1) osteitis fibrosa cystica (in patients with renal failure)


It is also important to make sure that there is not a problem in the erythropoietin therapy:

(1) inadequate dose

(2) improper administration

(3) inactive (or counterfeit) drug


To read more or access our algorithms and calculators, please log in or register.