Clinical meaning
Iron homeostasis is regulated by the hepcidin-ferroportin axis. Hepcidin, a hepatic peptide hormone, is the master regulator: it binds to ferroportin (the sole iron exporter on enterocytes and macrophages), causing its internalization and degradation, thereby reducing iron absorption and release from stores. In iron deficiency, hepcidin is suppressed, maximizing iron absorption. In anemia of chronic disease (ACD), inflammatory cytokines (IL-6) upregulate hepcidin, trapping iron in macrophages despite adequate stores—creating functional iron deficiency. The clinician must differentiate IDA from ACD, thalassemia trait, and sideroblastic anemia using advanced iron studies, prescribe appropriate iron formulations (oral vs. parenteral), investigate underlying etiology, and manage refractory cases.
Diagnosis & workup
Diagnostics & workup: - Order and interpret complete iron panel: serum iron, ferritin, TIBC, transferrin saturation (TSAT) - Differentiate IDA from ACD: IDA has low ferritin, high TIBC, low TSAT; ACD has normal/high ferritin, low TIBC, low TSAT - Order soluble transferrin receptor (sTfR) and calculate sTfR/log ferritin index to differentiate IDA from ACD in mixed presentations - Evaluate peripheral smear: microcytic hypochromic RBCs, anisocytosis (elevated RDW), target cells, pencil cells - Order hemoglobin electrophoresis if MCV is disproportionately low relative to anemia severity (consider thalassemia trait) - Order GI evaluation: upper endoscopy and colonoscopy for men, postmenopausal women, or anyone >40 with unexplained IDA - Order celiac panel (anti-tTG IgA) and H. pylori testing if malabsorption suspected - Consider hepcidin level in complex cases to guide oral vs. IV iron decision