EPO — Erythropoiesis-stimulating agent (ESA) — recombinant glycoprotein hormone

Boxed warnings added 2007 after CHOIR (CKD) and TREAT (diabetic CKD) trials showed increased mortality and cardiovascular events when targeting normal hemoglobin (13-14 g/dL). Current standard: target Hgb 10-12 g/dL, NEVER exceed 12 g/dL in cancer patients (increased tumor progression risk). Darbepoetin (Aranesp) has approximately 3x longer half-life vs epoetin enabling once-weekly or once-every-3-weeks dosing — this is the preferred formulation for convenience. Iron deficiency is the most common cause of EPO hyporesponsiveness — TSAT >20% and ferritin >100 ng/mL required before and during therapy. In performance doping context: EPO dramatically increases VO2max and was directly linked to multiple cycling deaths in the 1990s from nocturnal bradycardia with RBC sludging. The biological passport system (longitudinal tracking of hemoglobin and reticulocyte parameters) has largely eliminated overt EPO doping at elite athletic levels.