22/02/2026
Hepcidin — the iron gatekeeper
Hepcidin is the liver-derived peptide hormone that controls systemic iron: it binds ferroportin and blocks iron export from enterocytes and macrophages. When hepcidin is high, serum iron and transferrin-saturation fall even if body iron stores are normal — the core mechanism behind anemia of inflammation.
Why labs should care:
• Differential diagnosis power. Measured hepcidin helps distinguish true iron-deficiency anemia (low hepcidin) from anemia of chronic disease / functional iron deficiency (high or normal hepcidin), which directly affects whether oral iron will work. Multiple recent reviews and cohort studies support hepcidin as a useful adjunct in this problem set.
• Therapeutic prediction. Elevated hepcidin predicts poor response to oral iron and may help guide choice of IV iron or anti-inflammatory strategies in complex patients.
Assays — what labs should know before promising clinicians results:
• Two main families: mass-spectrometry (LC-MS/MS) and immunoassays. LC-MS methods are specific and harmonizable; commercial immunoassays are convenient but tend to read higher than MS and vary between platforms, especially in high inflammatory states. Know which method your lab will use and don’t mix numbers from different platforms.
• Standardization is improving but not perfect. Proficiency studies show intermethod variability — if you adopt hepcidin testing, plan a method comparison and participate in external QC.
Pre-analytics & reporting:
• Use the specimen and processing validated for your chosen assay (EDTA plasma vs serum), lock time-to-centrifuge, avoid hemolysis, aliquot and store at −80 °C for batch testing. Report specimen type and method with every result. Clinical interpretation without those metadata is risky.
How clinicians will use a hepcidin result:
• Low hepcidin + low ferritin/low TSAT → true iron deficiency — oral iron usually appropriate.
• High/normal hepcidin + low TSAT but normal/elevated ferritin → functional iron sequestration (inflammation, CKD) — consider IV iron or treat inflammation; oral iron likely to fail.
• Borderline cases → use hepcidin alongside ferritin, CRP, transferrin saturation and clinical context (infection, CKD, pregnancy, recent transfusion).
Practical rollout checklist for labs:
Decide use case (diagnostic reflex for borderline anemia, research, or clinic-requested test).
Choose method and run method-comparison against an external reference lab.
Lock pre-analytic SOPs and train collection staff.
Implement QC (pooled QCs, participate in proficiency testing).
Provide clear LIS guidance so clinicians know how to act on the result.
Does your lab run hepcidin? what single validation or pre-analytic snag would you warn others about?
