Iron Deficiency

The answer first

Iron deficiency is the commonest cause of anaemia in the world, the most over-investigated-yet-under-diagnosed number on the FBC, and — in an adult man or postmenopausal woman — a malignancy signal first and a haematinic deficiency second [1] [2]. Three rules carry you through almost every DWE question and every clinic letter:

1. Diagnose with ferritin and TSAT together, and never trust ferritin alone in inflammation. Ferritin below about 30 µg/L confirms iron deficiency; but ferritin is an acute phase reactant, so in any inflamed patient a "normal" ferritin means nothing — read it beside CRP and transferrin saturation, where TSAT below 20% unmasks deficiency the ferritin is hiding [1] [5].
2. Find the cause, and let the demographics choose the scope. Menstrual loss explains iron deficiency in a premenopausal woman until you prove otherwise; in men and postmenopausal women, occult GI blood loss is assumed and bidirectional endoscopy is the standard of care — iron tablets without gastroscopy and colonoscopy is the classic examination and medicolegal failure [5] [6].
3. Replace iron physiologically, and match the route to the gut. Oral iron first for most — once daily or alternate days, because each dose spikes hepcidin and blocks the next one. Intravenous iron when the gut cannot absorb it or the loss outruns it: active IBD, bariatric surgery, CKD, heart failure, intolerance or non-response [11] [12] [14].

---

References23Show ledgerHide ledger

1. [1]Camaschella C. Iron-deficiency anemia N Engl J Med, 2015.PMID 25946282
2. [2]Lopez A, Cacoub P, Macdougall IC, et al. Iron deficiency anaemia Lancet, 2016.PMID 26314490
3. [3]Ganz T. Systemic iron homeostasis Physiol Rev, 2013.PMID 24137020
4. [4]Camaschella C, Nai A, Silvestri L. Iron metabolism and iron disorders revisited in the hepcidin era Haematologica, 2020.PMID 31949017
5. [5]Snook J, Bhala N, Beales ILP, et al. British Society of Gastroenterology guidelines for the management of iron deficiency anaemia in adults Gut, 2021.PMID 34497146
6. [6]Rockey DC, Cello JP. Evaluation of the gastrointestinal tract in patients with iron-deficiency anemia N Engl J Med, 1993.PMID 8179652
7. [7]Ludvigsson JF, Bai JC, Biagi F, et al. Diagnosis and management of adult coeliac disease: guidelines from the British Society of Gastroenterology Gut, 2014.PMID 24917550
8. [8]Thomas DW, Hinchliffe RF, Briggs C, et al. Guideline for the laboratory diagnosis of functional iron deficiency Br J Haematol, 2013.PMID 23573815
9. [9]Punnonen K, Irjala K, Rajamäki A. Serum transferrin receptor and its ratio to serum ferritin in the diagnosis of iron deficiency Blood, 1997.PMID 9028338
10. [10]Mentzer WC Jr. Differentiation of iron deficiency from thalassaemia trait Lancet, 1973.PMID 4123424
11. [11]Moretti D, Goede JS, Zeder C, et al. Oral iron supplements increase hepcidin and decrease iron absorption from daily or twice-daily doses in iron-depleted young women Blood, 2015.PMID 26289639
12. [12]Stoffel NU, Cercamondi CI, Brittenham G, et al. Iron absorption from oral iron supplements given on consecutive versus alternate days and as single morning doses versus twice-daily split dosing in iron-depleted women: two open-label, randomised controlled trials Lancet Haematol, 2017.PMID 29032957
13. [13]Hershko C, Camaschella C. How I treat unexplained refractory iron deficiency anemia Blood, 2014.PMID 24215034
14. [14]Dignass AU, Gasche C, Bettenworth D, et al. European consensus on the diagnosis and management of iron deficiency and anaemia in inflammatory bowel diseases J Crohns Colitis, 2015.PMID 25518052
15. [15]Macdougall IC, Bock AH, Carrera F, et al. FIND-CKD: a randomized trial of intravenous ferric carboxymaltose versus oral iron in patients with chronic kidney disease and iron deficiency anaemia Nephrol Dial Transplant, 2014.PMID 24891437
16. [16]Macdougall IC, White C, Anker SD, et al. Intravenous Iron in Patients Undergoing Maintenance Hemodialysis N Engl J Med, 2019.PMID 30365356
17. [17]Anker SD, Comin Colet J, Filippatos G, et al. Ferric carboxymaltose in patients with heart failure and iron deficiency N Engl J Med, 2009.PMID 19920054
18. [18]Ponikowski P, Kirwan BA, Anker SD, et al. Ferric carboxymaltose for iron deficiency at discharge after acute heart failure: a multicentre, double-blind, randomised, controlled trial Lancet, 2020.PMID 33197395
19. [19]Kalra PR, Cleland JGF, Petrie MC, et al. Intravenous ferric derisomaltose in patients with heart failure and iron deficiency in the UK (IRONMAN): an investigator-initiated, prospective, randomised, open-label, blinded-endpoint trial Lancet, 2022.PMID 36347265
20. [20]Wolf M, Chertow GM, Macdougall IC, et al. Randomized trial of intravenous iron-induced hypophosphatemia JCI Insight, 2018.PMID 30518682
21. [21]Schaefer B, Tobiasch M, Viveiros A, et al. Hypophosphataemia after treatment of iron deficiency with intravenous ferric carboxymaltose or iron isomaltoside-a systematic review and meta-analysis Br J Clin Pharmacol, 2021.PMID 33188534
22. [22]Allen RP, Picchietti DL, Auerbach M, et al. Evidence-based and consensus clinical practice guidelines for the iron treatment of restless legs syndrome/Willis-Ekbom disease in adults and children: an IRLSSG task force report Sleep Med, 2018.PMID 29425576
23. [23]Aills L, Blankenship J, Buffington C, et al. ASMBS Allied Health Nutritional Guidelines for the Surgical Weight Loss Patient Surg Obes Relat Dis, 2008.PMID 18490202