A patient-oriented approach to the clinical use of rHuEpo in anemic patients or individuals who are very likely to become anemic. The use of rHuEpo should be limited to patients with symptomatic anemia and those who are transfusion-dependent or candidates for blood transfusion. This approach does not apply to the anemia of prematurity (see the pertinent section). Treatment should be considered only after the nature of the anemia has been clearly established. Furthermore, before using rHuEpo, other concomitant, correctable causes of anemia such as iron deficiency or folate/vitamin B₁₂ deficiency should be recognized and remedied. Treatment should be started only after an inadequate Epo production has been documented, with the exception of patients undergoing chemotherapy, who may still have adequate endogenous Epo production but are likely to develop a defective one. Several studies have shown that a cutoff for serum Epo of 100 mU/mL allows the best discrimination between responders and nonresponders.51,54,154,156 This threshold has a high predictive power for Hb values less than 10 g/dL.54 For higher Hb values, the use of a threshold of 0.9 for the O/P ratio should be preferred. For AIDS patients, the most useful serum Epo level for deciding treatment has been found to be 500 mU/mL.132 Iron supplements should be routinely provided to prevent functional iron deficiency during the first 4 to 6 weeks, except in patients with iron overload and increased transferrin saturation. A safe preparation of IV iron is superior to oral iron. If iron saccharate is available, 100 mg should be administered by IV infusion three times weekly for 3 to 4 weeks. An impaired iron supply to the erythroid marrow will blunt the erythropoietic response to rHuEpo; “unresponsive” patients may become “responsive” after correction of the functional iron deficiency. Indicators of early response might allow clinicians to decide whether to continue or terminate rHuEpo therapy after 4 weeks. Changes in Hb concentration51,178 and reticulocyte count54 proved to be useful indicators for this purpose. These changes should be examined after 4 weeks of treatment in patients who do not receive concomitant chemotherapy and/or blood transfusion; for those who receive these concomitant treatments and are less likely to respond quickly, a second check after 8 weeks may be appropriate.