Delayed hepcidin response explains the lag period in iron absorption following a stimulus to increase erythropoiesis

Abstract

Introduction: The delay of several days between an erythropoietic stimulus and the subsequent increase in intestinal iron absorption is commonly believed to represent the time required for body signals to programme the immature crypt enterocytes and for these cells to migrate to the villus. Recent data however suggest that signals from the body to alter absorption are mediated by circulating hepcidin and that this peptide exerts its effect on mature villus enterocytes. Methods: We have examined the delay in the absorptive response following stimulated erythropoiesis using phenylhydrazine induced haemolysis and correlated this with expression of hepcidin in the liver and iron transporters in the duodenum. Results: There was a delay of four days following haemolysis before a significant increase in iron absorption was observed. Hepatic hepcidin expression did not decrease until day 3, reaching almost undetectable levels by days 4 and 5. This coincided with the increase in duodenal expression of divalent metal transporter 1, duodenal cytochrome b, and Ireg1. Conclusion: These results suggest that the delayed increase in iron absorption following stimulated erythropoiesis is attributable to a lag in the hepcidin response rather than crypt programming, and are consistent with a direct effect of the hepcidin pathway on mature villus enterocytes.

3rd Mediterranean Multidisciplinary Course on Iron Anemia

“…The procedures in orthopedic and trauma surgery (OST), vascular or oncological surgery can cause significant blood loss and provoke a postoperative acute anemia, or aggravate previous preoperative anemia, which often requires ABT. The clinical, financial and logistical disadvantages of ABT have promoted the development of generically known as Patient Blood Management programs (PBM) multidisciplinary and multimodal programs whose aim is to reduce or eliminate the need for ABT and improve clinical outcome [3,6,7]. These programs are supported by the application of four groups of perioperative measures: use of "restrictive" transfusion criteria (administer the minimum effective dose guided by clinical signs o symptoms); stimulation of erythropoiesis (diagnosing and treating the perioperative anemia); reducing bleeding (improving the hemostasis and avoiding the hyperfibrinolysis); and autologous blood transfusion [3].…”

“…Standard operating procedures, multimodal strategies and protocols are needed to improve the Hb perioperative levels to avoid (or to reduce to minimum) ABT and to achieve the best clinical outcome. Patient blood management [3,6,7]: PBM is an evidencebased approach to optimizing the care of patients who could or might need transfusion. A focus on improved patient outcomes and economic and operational pressures are leading key industry thinkers to examine appropriate blood usage with new interest.…”

“…Hospitals are eager to improve patient safety and clinical outcomes, while also reducing the need for allogeneic blood components. PBM programs can achieve these goals by reducing variation in transfusion practice and managing patients with nontransfusionand, if appropriate, transfusion -treatment modalities [7].…”

“…Thus, hepcidin levels may be useful in differentiating between FID and FID+ID and have been also shown useful in predicting non-responsiveness to oral iron salts in patients with IDA [7]. As for individuals resistant to conventional oral iron therapy, the use of iv.…”

“…The reason of failure of oral iron formulation in cancer anemic patients seems related to the hepcidin protein, an acute phase protein produced primarily by the liver. Several observation suggest that hepcidin, and perhaps other regulatory molecules produced in the liver [3][4][5], plays a major role as a negative regulator of intestinal iron absorption and iron release from macrophages [6,7], by interacting with, and inactivating, the iron export protein ferroportin [8]. If chemotherapy and radiotherapy are the main reasons for cancer-associated anemia, several other agents or conditions in cancer patients can interfere with erythropoiesis.…”