HUSAIN ALKHALDY · HOW I TREAT  —  IRON DEFICIENCY ANAEMIA

How I treat iron deficiency anaemia

Husain Alkhaldy

HaematologyEvidence to September 2026

Introduction

Iron deficiency anaemia affects more than 1.2 billion people worldwide, and iron deficiency without anaemia is even more common 1. It is also a condition in which the diagnosis, the cause and the treatment are separate tasks, and each can be missed while the others are done well.

In Saudi Arabia the burden is large. A national epidemiological survey of 981 people in four regions found iron deficiency in 28.6% and iron deficiency anaemia in 10.7%; 94.1% of those with iron deficiency anaemia were women 2. A 2026 systematic review brought together eight cross-sectional studies, with 26,412 participants, on the prevalence of anaemia and iron deficiency anaemia in the Kingdom and the factors behind them 3. A private-sector laboratory dataset of 420,956 people from 13 regions, using a ferritin threshold of 30 µg/L, reported iron deficiency anaemia in 19.8% and iron deficiency without anaemia in 23.7% 4. In the southern highlands, a study of 200 female medical students found iron deficiency in 63% 5.

This article follows four cases: a young woman whose poor diet adds to her menstrual losses; a woman with heavy menstrual bleeding and a suspected bleeding disorder; a pregnant woman; and a patient awaiting surgery. The four cases are illustrative composites, not individual patients. Each is answered from what the guidelines recommend and from the evidence behind them, and where the guidelines differ, the difference is stated.

What the guidelines say

Five current documents shape the management of iron deficiency in adults, and each was written for a different reader. Two come from gastroenterology societies, one from a haematology society, one from an obstetric federation and one from a peri-operative consensus group. All five read iron stores from serum ferritin, with or without transferrin saturation (TSAT). They differ on the ferritin threshold, and they differ on how far they address treatment at all (Table 1).

Most guidelines recommend oral iron first. BSG 2021 and FIGO 2023 do so for the populations they cover, and the peri-operative consensus does so when surgery is at least six to eight weeks away 6–8. AGA 2020 places the choice of route outside its scope, and ASH's 2026 guideline covers diagnosis only 9,10. No guideline on iron deficiency anaemia from the Saudi Ministry of Health or the Saudi Commission for Health Specialties could be found. The Saudi literature on the subject consists of prevalence studies.

Table 1 · Five current guidelines on iron deficiency: population, diagnostic thresholds and route of treatment

GuidelineScope and populationFerritin threshold(s)Other criteriaFirst-line routeWhen intravenous
BSG 2021 6Adults with iron deficiency anaemia; gastroenterology<15 µg/L highly specific; <30 µg/L generally indicative; 45 µg/L the optimal trade-off; lower limit of normal in the range 15–30 µg/LFerritin >150 µg/L makes deficiency unlikely even with inflammationOral: one tablet a day of a ferrous salt; if not tolerated, alternate days, another oral preparation, or parenteral ironOral iron contraindicated, ineffective or not tolerated; early when correction is urgent
AGA 2020 9,11Adults with iron deficiency anaemia; gastrointestinal evaluation45 µg/L preferred over 15 µg/LCoeliac serology; non-invasive H. pylori testing after a negative bidirectional endoscopyOutside scopeOutside scope
ASH 2026 10Diagnosis only; children, adults, menstruating and pregnant individuals≤20 µg/L children 9 months–4 years; ≤30 µg/L most adults, menstruating and pregnant individuals; ≤50 µg/L high-risk groups (heavy menstrual bleeding, anaemic pregnancy)With inflammation: ferritin <100 µg/L or TSAT <20%Not addressed; treatment guideline expected in 2027Not addressed
FIGO 2023 7Women and girls, from menarcheFerritin and/or TSAT; no single numeric threshold in the recommendationsAnaemia described as a late sign of iron deficiencyOral for iron deficiency and mild to moderate anaemia; alternate-day dosing for intolerance or non-responseIn pregnancy, from the second trimester, for non-response, intolerance, poor compliance, moderate to severe anaemia, anaemia within 4–6 weeks of delivery, or malabsorption; not advised in the first trimester
International peri-operative consensus 2017 8Adults before and after surgery<30 µg/L: iron deficiency; 30–100 µg/L with TSAT <20% and/or CRP >5 mg/L: functional deficiency; <100 µg/L: treatment trigger before surgery with moderate to high expected blood lossFerritin >100 µg/L with TSAT <20%: iron sequestration; target Hb ≥13.0 g/dL in both sexesOral if surgery is ≥6–8 weeks awaySurgery <6 weeks away; intolerance, contraindication or no response to oral iron

AGA 2020 and ASH 2026 report ferritin in ng/mL, which is numerically the same as µg/L. BSG, British Society of Gastroenterology; AGA, American Gastroenterological Association; ASH, American Society of Hematology; FIGO, International Federation of Gynecology and Obstetrics; TSAT, transferrin saturation; CRP, C-reactive protein.

Two guidelines for particular groups sit beside these five: heart failure and inflammatory bowel disease (Table 2).

Table 2 · Guidelines for two particular groups

GuidelineScope and populationDiagnostic criteriaFirst-line routeWhen intravenous
ESC 2023 12Heart failureIndependent of anaemia: ferritin <100 µg/L, or 100–299 µg/L with TSAT <20%Intravenous; oral iron not recommended for this indicationFerric carboxymaltose or ferric derisomaltose: recommended for symptoms and quality of life, considered to reduce heart failure admissions
ECCO 2015 13Inflammatory bowel diseaseNot summarised hereIntravenous in active or moderate to severe diseaseActive disease, Hb <10 g/dL, or oral iron ineffective or not tolerated — each an independent trigger

ESC, European Society of Cardiology; ECCO, European Crohn's and Colitis Organisation.

British Society of Gastroenterology, 2021

The BSG guideline covers adults with iron deficiency anaemia and is the most detailed of the five on diagnosis and treatment 6. It gives a graded set of ferritin thresholds. A ferritin below 15 µg/L is highly specific (specificity 0.99); below 30 µg/L is generally indicative; and 45 µg/L is suggested as the optimal trade-off (specificity 0.92). It places the lower limit of normal in the range 15–30 µg/L and treats a ferritin above 150 µg/L as making deficiency unlikely even when inflammation is present.

On treatment, BSG recommends oral iron first, one tablet a day of a ferrous salt. If that is not tolerated, it suggests alternate-day dosing, a different oral preparation, or parenteral iron. Parenteral iron is for patients in whom oral iron is contraindicated, ineffective or not tolerated, and it may be started early when correction is urgent. The guideline sets no numeric ferritin target for repletion and names this as an unresolved question.

American Gastroenterological Association, 2020

The AGA guideline, with its companion technical review, addresses one question: how to evaluate the gastrointestinal tract in a patient with iron deficiency anaemia 9,11. It prefers a ferritin cut-off of 45 µg/L to 15 µg/L, with a sensitivity of about 85% and a specificity of about 92% 9. It recommends coeliac serology for all patients with iron deficiency anaemia and non-invasive testing for Helicobacter pylori after a negative bidirectional endoscopy 11. Treatment is excluded by design: "addressing the type of iron therapy and route of treatment … was outside the scope of this review" 9. No separate guideline from the American College of Gastroenterology was found; AGA 2020 is the position of US gastroenterology on this topic.

American Society of Hematology, 2026

ASH's 2026 diagnosis guideline, published in September 2026, is the society's first guideline on iron deficiency 10. It deals with diagnosis only; a treatment guideline is expected in 2027. It sets thresholds by group rather than one number for everyone: ferritin ≤20 µg/L in children aged 9 months to 4 years; ≤30 µg/L in most adults and in menstruating and pregnant individuals; and ≤50 µg/L in groups at high risk, including heavy menstrual bleeding and pregnancy with anaemia. When inflammation is present, it accepts a ferritin below 100 µg/L or a TSAT below 20%.

International Federation of Gynecology and Obstetrics, 2023

FIGO's statement covers women and girls from menarche onward 7. It recommends assessing iron status with ferritin and/or TSAT and gives no single numeric threshold in its recommendations. It describes anaemia as a late sign of iron deficiency. On treatment it is explicit: "The first-line intervention for ID and mild to moderate IDA is oral iron therapy," with alternate-day dosing offered for intolerance or non-response. In pregnancy it does not advise parenteral iron in the first trimester, and from the second trimester it lists the indications for intravenous iron shown in Table 1. Its wording on the first trimester is quoted under Pregnancy.

International consensus on peri-operative anaemia, 2017

The 2017 international consensus statement, published in Anaesthesia, covers adults before and after surgery 8. It defines iron deficiency as a ferritin below 30 µg/L (sensitivity 92%, specificity 98%), sets two further bands for functional iron deficiency and iron sequestration, and uses a ferritin below 100 µg/L as a treatment trigger before surgery with moderate to high expected blood loss (Table 1). The bands are set out under Transferrin saturation and inflammation, and the trigger and the haemoglobin target under Before surgery.

The consensus recommends oral iron (40–60 mg a day, or 80–100 mg on alternate days) when surgery is six to eight weeks or more away. It recommends intravenous iron when surgery is less than six weeks away or when oral iron is not tolerated, contraindicated or ineffective. It keeps the Ganzoni formula for the total iron deficit. The statement grew out of a workshop sponsored by Pharmacosmos, a manufacturer of intravenous iron, and several of its authors disclose honoraria.

European Society of Cardiology, 2023 (heart failure)

The ESC defines iron deficiency in heart failure without reference to haemoglobin: a ferritin below 100 µg/L, or 100–299 µg/L with a TSAT below 20% 12. Treatment is intravenous only. Intravenous iron supplementation is recommended in patients with heart failure and iron deficiency to improve symptoms and quality of life, and should be considered to reduce the risk of hospitalisation for heart failure; oral iron is not recommended for this indication 12.

European Crohn's and Colitis Organisation, 2015 (inflammatory bowel disease)

ECCO's statement 2C recommends intravenous iron first line in patients with clinically active inflammatory bowel disease, in those with a haemoglobin below 10 g/dL, and in those with previous intolerance to oral iron — each an independent trigger, not a combination 13.

Where the guidelines agree and differ

The guidelines agree that iron stores are read from serum ferritin, with TSAT when inflammation may raise the ferritin. They differ on the ferritin threshold (Table 1) and on the route of treatment. BSG 2021 and FIGO 2023 recommend oral iron first, and the peri-operative consensus does so when surgery is six to eight weeks or more away 6–8. The ESC recommends intravenous iron, not oral iron, in heart failure 12, and ECCO puts intravenous iron first in active inflammatory bowel disease 13. AGA 2020 places the route outside its scope, and ASH 2026 covers diagnosis only 9,10. The evidence on the two routes is set out under Oral or intravenous iron, and the evidence on treating iron deficiency without anaemia under Iron deficiency without anaemia.

Four cases

Each of these four patients raises a different question about when and how to replace iron. Case 1 is taken up under Diet, Case 2 under Heavy menstrual bleeding and bleeding disorders, Case 3 under Pregnancy and Case 4 under Before surgery.

Case 1 — A student who is always tired

A 20-year-old university student has felt tired for six months and can no longer keep up with her friends on the stairs. Her periods are regular and last six days; she does not think they are heavy. She skips breakfast, eats meat perhaps once a week. She is pale but otherwise well. Haemoglobin is 10.6 g/dL, MCV 73 fL and ferritin 6 µg/L. Her diet and her periods both take iron away from her. Does the diet change how she should be treated?

Case 2 — Heavy periods since menarche

A 31-year-old teacher has had heavy periods since her first one at the age of 12. She passes clots, changes pads through the night and misses work on the first two days of each cycle. Her pictorial blood loss chart scores well above 100. As a child she had nosebleeds that needed packing, and she bled for two days after a dental extraction. Her sister has the same kind of periods. Haemoglobin is 9.8 g/dL and ferritin 4 µg/L. Her iron can be replaced, but it will run out again. Does she have a bleeding disorder, and who treats what?

Case 3 — Nine weeks pregnant

A 27-year-old woman in her second pregnancy is nine weeks pregnant. Her first child is 14 months old and she breastfed until recently. She is breathless climbing to her flat and has little appetite because of nausea. Haemoglobin is 9.2 g/dL, MCV 71 fL and ferritin 5 µg/L. Her obstetrician has asked whether iron can wait until the second trimester. Can it, and if not, which iron is acceptable this early?

Case 4 — Four weeks before a colectomy

A 58-year-old man had a colonoscopy for iron deficiency anaemia, which found a cancer in the right colon. He is booked for a right hemicolectomy in four weeks. He is well apart from tiredness. Haemoglobin is 10.4 g/dL, ferritin 14 µg/L, transferrin saturation 8% and CRP normal. The cause of his iron deficiency is known and is about to be removed. The surgeon wants him in the best state for theatre. Is four weeks long enough, and will correcting his iron change what happens to him?

Diagnosis

The diagnosis rests on serum ferritin, read with TSAT when inflammation is present, and it is not complete until the cause is known. At altitude, WHO adjusts the haemoglobin threshold for anaemia; its adjustment does not apply to ferritin.

Ferritin

Serum ferritin settles the diagnosis in most patients. The thresholds differ between sources (Table 1), and the difference reflects a trade between sensitivity and specificity. BSG treats a ferritin below 15 µg/L as highly specific, below 30 µg/L as generally indicative, and 45 µg/L as the optimal trade-off 6. AGA prefers 45 µg/L to 15 µg/L 9. The peri-operative consensus uses 30 µg/L 8. ASH's 2026 guideline uses ≤30 µg/L for most adults and ≤50 µg/L for high-risk groups 10. If the young woman in Case 1 has heavy periods, ASH places her in the high-risk group, and the threshold that applies to her rises from 30 to 50 µg/L.

None of these numbers is a fact of biology. Each is an agreed point on a continuous curve, and a patient whose ferritin sits just above one threshold may sit below another. WHO's 2024 altitude adjustment applies to haemoglobin, not to ferritin (Altitude).

Transferrin saturation and inflammation

Ferritin rises with inflammation, so a normal ferritin does not exclude iron deficiency in a patient with an inflammatory illness. TSAT is then read alongside it. The peri-operative consensus gives three bands: ferritin below 30 µg/L is iron deficiency; 30–100 µg/L with a TSAT below 20% and/or a CRP above 5 mg/L is functional iron deficiency; and above 100 µg/L with a TSAT below 20% is iron sequestration 8. ASH accepts a ferritin below 100 µg/L or a TSAT below 20% as diagnostic when inflammation is present 10. BSG regards a ferritin above 150 µg/L as making deficiency unlikely even with inflammation 6. The sequestration band points toward anaemia of inflammation, which is outside this article (Anaemia of inflammation).

Finding the cause

Iron deficiency has a cause, and the diagnosis is not complete until the cause is known. AGA 2020 recommends coeliac serology for every patient with iron deficiency anaemia, and that includes a young woman whose menstrual history and diet seem to explain the deficiency 11. AGA also recommends non-invasive testing for Helicobacter pylori when bidirectional endoscopy is negative 11. If her history suggests heavy menstrual bleeding or a bleeding tendency, the approach in Case 2 applies.

When iron deficiency is unexplained, or fails to respond to treatment, the list of causes widens. In their Blood review of unexplained refractory iron deficiency anaemia, Hershko and Camaschella report coeliac disease in 4–6% of such patients, autoimmune gastritis in 20–27%, and active H. pylori infection in more than half; they report that 64–75% of those with H. pylori were permanently cured after treatment 14.

Altitude

People who live at altitude have higher haemoglobin concentrations, and WHO's 2024 guideline on haemoglobin cut-offs adjusts its thresholds for elevation 15. WHO gives its adjustment in bands of 500 m; for the band of 2,000–2,499 m, which includes Abha at about 2,270 m, it adds 14 g/L, about 1.4 g/dL, to the sea-level threshold 15. The adjustment applies to haemoglobin. WHO's 2020 guideline on the use of ferritin to assess iron status does not address altitude 66.

The study of 200 female medical students in high-altitude southern Saudi Arabia chose its own altitude-adjusted threshold, haemoglobin below 13 g/dL for women, and kept ferritin cut-offs unadjusted 5. On those definitions it found iron deficiency anaemia (haemoglobin below 13 g/dL with ferritin below 15 µg/L) in 17.5%, iron deficiency in 63%, and a ferritin below 15 µg/L in 52.5% 5.

The figures differ because each is a choice. A haemoglobin threshold for anaemia is a convention, and an altitude adjustment is a convention placed on top of it.

The approach in brief

Figure 1 brings the pathway together, from suspicion to follow-up.

The approach to iron deficiency in brief Flow chart. Suspected iron deficiency leads to a full blood count and ferritin, with transferrin saturation and CRP where inflammation may hide a low ferritin. The haemoglobin threshold for anaemia is adjusted for altitude; WHO 2024 adds 1.4 g/dL at 2,000–2,499 m. The ferritin threshold depends on the guideline, with transferrin saturation read alongside it when inflammation is present. Iron deficiency with or without anaemia leads to a search for the cause; BSG regards treatment of symptomatic iron deficiency without anaemia as reasonable. Iron is then replaced: oral iron first in most guidelines, with intravenous iron first in heart failure and active inflammatory bowel disease, and used for intolerance, failure, urgency or surgery less than six weeks away. Every intravenous dose is followed by at least 30 minutes of observation. Two branches join here: pregnancy, where FIGO places intravenous iron from the second trimester and there are no safety data for the first, and the pre-operative patient, with a target haemoglobin of at least 13 g/dL. Follow-up comes last. Suspected iron deficiency FBC and ferritin TSAT and CRP where inflammation may hide a low ferritin Haemoglobin threshold Altitude-adjusted (WHO 2024) +1.4 g/dL at 2,000–2,499 m Ferritin Threshold by guideline with TSAT if inflamed Iron deficiency, with or without anaemia Find the cause; treat symptomatic NAID (BSG) Find the cause History: diet, menstrual loss, gastrointestinal symptoms Coeliac serology Gastrointestinal investigation as indicated Bleeding-disorder screen in heavy menstrual bleeding Replace iron Most guidelines: oral first; IV first in HF, active IBD IV for intolerance, failure, urgency, surgery <6 wk Observe at least 30 min after each IV dose Pregnancy IV from 2nd trimester (FIGO) 1st trimester: no safety data Before surgery Target haemoglobin at least 13 g/dL Follow-up Maximal response at about 3 weeks · cause dealt with
Figure 1 · The approach to iron deficiency in brief. The altitude adjustment for haemoglobin is WHO's 2024 guideline 15; the ferritin thresholds are in Table 1 6–10. Treatment of symptomatic iron deficiency without anaemia (NAID) follows BSG 2021 6. The route follows BSG, FIGO, the peri-operative consensus, the ESC heart failure guideline (HF) and ECCO for inflammatory bowel disease (IBD) 6–8,12,13; the observation after each dose is the EMA requirement 30. The pregnancy branch follows FIGO 2023 and the iron sucrose labels 7,25,31. The pre-operative target and the response timeline are from the 2017 international consensus 8. The dashed boxes are special situations that feed into the same treatment.

Intravenous iron

Iron replacement treats the deficit but not its cause, so the work-up comes first. Once the cause is found or being dealt with, the questions are practical: which route, which product, how much, and where to give it.

Oral or intravenous iron

Most guidelines recommend oral iron first: BSG 2021 and FIGO 2023 for the populations they cover, and the peri-operative consensus when surgery is six to eight weeks or more away 6–8. Intravenous iron comes first in heart failure and in active inflammatory bowel disease 12,13. The evidence that bears on the choice concerns tolerance, absorption and efficacy.

On tolerance, the clearest figure is from a meta-analysis of randomised trials in adults. Ferrous sulphate caused significantly more gastrointestinal side effects than placebo (odds ratio 2.32, 95% CI 1.74–3.08; 20 trials, 3,168 patients) and than intravenous iron (odds ratio 3.05, 95% CI 2.07–4.48; 23 trials, 3,663 patients) 17. The pooled rates were 12% for constipation, 11% for nausea and 8% for diarrhoea 17. A meta-analysis of 103 randomised trials of intravenous iron found the same pattern from the other side: against oral iron, intravenous iron gave fewer gastrointestinal adverse events (relative risk 0.33, 95% CI 0.29–0.38) and more infusion reactions (relative risk 3.49, 95% CI 2.22–5.49) 61.

On absorption, the studies explain why a tablet a day is an inefficient way to replace iron. In iron-depleted young women, single oral doses of 60 mg or more raised hepcidin, and fractional absorption of the next day's dose fell by 35–45%. A six-fold increase in dose, from 40 to 240 mg, gave only about three times as much absorbed iron 18. A second trial found cumulative fractional absorption of 21.8% with alternate-day dosing against 16.3% with consecutive-day dosing 19. Both papers argue for alternate-day dosing as the more efficient schedule 18,19.

On efficacy, a Cochrane review of anaemic adults without chronic kidney disease found haemoglobin higher with parenteral than with oral iron, by a mean difference of 0.50 g/dL (95% CI 0.27–0.73; six studies, 769 participants), on very low-quality evidence 63. All the trials were at high risk of bias, and the authors concluded that parenteral iron gives a modest increase in haemoglobin without demonstrated clinical benefit 63. The evidence in pregnancy is set out under Pregnancy.

Studies of iron and the gut microbiome come mostly from iron fortification in infants and children in low-income countries, where the effects were more pronounced in settings with poor hygiene 16; their relevance to adults treated for iron deficiency anaemia is uncertain.

Indications

BSG 2021 regards treatment of symptomatic iron deficiency without anaemia as reasonable 6; the trials behind that view are in Iron deficiency without anaemia.

For intravenous iron, BSG 2021 advises parenteral iron when oral iron is "contraindicated, ineffective or not tolerated", and earlier when oral iron is judged unlikely to work or correction is urgent 6. The 2017 international consensus on peri-operative anaemia advises intravenous iron when surgery is less than six weeks away, when oral iron is not tolerated, is contraindicated or has failed, and when there is functional iron deficiency with inflammation 8. The European Society of Cardiology's 2023 heart failure update recommends intravenous iron, not oral iron, for iron deficiency in heart failure, and defines deficiency there as a ferritin below 100 µg/L, or 100–299 µg/L with a transferrin saturation below 20% 12. The 2015 European consensus on inflammatory bowel disease puts intravenous iron first in active disease, when haemoglobin is below 10 g/dL, or when oral iron has failed or is not tolerated — each its own trigger 13.

Three randomised trials give evidence in particular groups. In AFFIRM-AHF, ferric carboxymaltose given at discharge after acute heart failure reduced heart failure hospitalisations, 217 against 294 with placebo (rate ratio 0.74, 95% CI 0.58–0.94) 20. In IRONMAN, ferric derisomaltose in heart failure with iron deficiency gave a rate ratio of 0.82 (95% CI 0.66–1.02) for the primary endpoint. That result was not significant, and the trial was affected by the COVID-19 pandemic 21. In PIVOTAL, among patients on maintenance haemodialysis, a proactive high-dose intravenous iron regimen was non-inferior to a reactive low-dose regimen for death and major cardiovascular events, with no increase in infections 22. These trials were done in heart failure and dialysis, not in the patients this article is about.

Choosing a formulation

Three products carry most of the evidence: ferric carboxymaltose, ferric derisomaltose and iron sucrose. They differ in how much iron each label allows at one visit. The ferric carboxymaltose label allows a single dose of up to 15 mg/kg by injection or 20 mg/kg by infusion, to a maximum of 1,000 mg, and no more than 1,000 mg in a week 23. The ferric derisomaltose label allows a single infusion of up to 20 mg/kg, or a single bolus injection of up to 500 mg 24. The iron sucrose label limits a single dose to 200 mg, given up to three times a week 25.

The clearest difference between products is hypophosphataemia. In the PHOSPHARE-IDA trials, serum phosphate fell below 2.0 mg/dL in 74.4% of patients given ferric carboxymaltose and in 8.0% of those given ferric derisomaltose. Severe hypophosphataemia, 1.0 mg/dL or less, occurred in 11.3% and 0% 26.

On hypersensitivity the evidence does not agree. A meta-analysis of randomised trials found serious or severe reactions in 1.08% of patients given ferric carboxymaltose (29 of 2,683, 7 trials) and in 0.14% of those given ferric derisomaltose (5 of 3,474, 10 trials), a statistically significant difference 27. A ten-year cohort from the US Veterans Health Administration, covering 162,457 exposures, points the other way: ferric carboxymaltose had the lowest rate of documented adverse reactions of the products compared, at 0.24% 28. The two sources differ in design. One pools trials; the other counts reactions recorded in routine care. Neither settles the question. For ferric derisomaltose against iron sucrose, the FERWON-IDA and FERWON-NEPHRO trials are the direct randomised comparison of safety 29.

No peer-reviewed trial comparing all three products head to head was found. The choice weighs the convenience of giving the whole dose at one visit against the risk of hypophosphataemia, and the hypersensitivity data remain unsettled. The first trimester of pregnancy is discussed under Pregnancy.

Total dose

The 2017 international consensus calculates the deficit with the Ganzoni formula 8:

Total iron deficiency [mg] = (Target Hb − Baseline Hb [g/L]) × 0.24 × Body weight [kg] + 500

The formula uses haemoglobin in g/L, so 13.0 g/dL is entered as 130. Before surgery the consensus target is at least 130 g/L in both sexes 8. Outside surgery there is no agreed target, and BSG 2021 calls the question of repletion unresolved 6.

As arithmetic only, with illustrative inputs: a 60 kg patient with a haemoglobin of 90 g/L and a target of 130 g/L has a calculated deficit of (130 − 90) × 0.24 × 60 + 500 = 576 + 500 = 1,076 mg. The label limits of the chosen product then decide whether that dose is given at one visit or divided.

Setting

The European Medicines Agency's 2013 review sets the conditions for any setting. Trained staff and resuscitation facilities must be available. Patients are observed for hypersensitivity during each injection and for at least 30 minutes after it 30.

Pregnancy

In Case 3, the woman is iron deficient and anaemic at nine weeks, and her obstetrician has asked whether iron can wait until the second trimester.

The European and UK summary of product characteristics for Venofer, the reference iron sucrose product, states: "There is no data from the use of iron sucrose in pregnant women in the first trimester." It adds: "Venofer should not be used during pregnancy unless clearly necessary," and confines use to the second and third trimesters "if the benefit is judged to outweigh the potential risk" 25. The US Venofer label states: "Available reports of intravenous iron sucrose use in pregnant women during the first trimester are insufficient to assess the risk of major birth defects and miscarriage" 31. The Saudi Food and Drug Authority leaflet for Ferosac, which is iron sucrose made in Saudi Arabia, states: "Ferosac has not been tested in women who are in the first three months of their pregnancy." The same leaflet recommends restricting use to the second and third trimesters when the benefit justifies the risk 32. Neither Venofer label lists the first trimester as a contraindication; both describe an absence of data 25,31.

FIGO's 2023 statement on iron deficiency in women and girls says: "Parenteral iron is not advised in the first trimester owing to a lack of safety data" 7. It places intravenous iron from the second trimester, for non-response, intolerance, poor compliance, moderate-to-severe iron deficiency anaemia, iron deficiency anaemia within four to six weeks of expected delivery, or malabsorption 7. Ferric carboxymaltose's UK summary of product characteristics likewise confines treatment in pregnancy to the second and third trimester, when the benefit is judged to outweigh the risk, and notes that iron deficiency occurring in the first trimester can often be treated with oral iron 23.

Beyond the first trimester there is randomised evidence. A three-arm trial in India randomised about 4,368 women at 14–17 weeks of gestation to ferric carboxymaltose, ferric derisomaltose or oral iron. Low birthweight occurred in 25.2% after ferric carboxymaltose against 29.3% after oral iron, a significant reduction; the rate after ferric derisomaltose was 29.1%, not significantly different from oral iron 33. On tolerance, Tolkien's meta-analysis found that ferrous sulphate caused significantly more gastrointestinal side effects than placebo or intravenous iron, and the excess held in its subgroup of pregnant women (odds ratio 3.33, p=0.02) 17.

Two meta-analyses compare intravenous with oral iron in pregnancy. A 2024 Cochrane review of 13 randomised trials, with 3,939 women at 13–37 weeks, found haemoglobin 0.49 g/dL higher with intravenous iron at 3–6 weeks (95% CI 0.28–0.69; moderate certainty). It found little or no difference in blood transfusion (risk ratio 0.97, 95% CI 0.58–1.60), and the effect on serious adverse events was uncertain (risk ratio 1.25, 95% CI 0.61–2.59; one trial, low certainty) 64. A 2026 meta-analysis of 29 randomised trials, with 11,771 participants, found haemoglobin at delivery 0.59 g/dL higher with intravenous iron (95% CI 0.31–0.87), fewer transfusions (risk ratio 0.63, 95% CI 0.49–0.82) and fewer mild adverse effects (risk ratio 0.56, 95% CI 0.41–0.76) 65. The two disagree on transfusion. Neither gives an estimate for the first trimester 64,65.

For Case 3, FIGO does not advise parenteral iron in the first trimester because of a lack of safety data, the iron sucrose labels report no data for that period, and the ferric carboxymaltose label notes that iron deficiency in the first trimester can often be treated with oral iron 7,23,25,31,32. On these documents, the first-trimester option is oral iron, and intravenous iron becomes available from the second trimester for non-response, intolerance, poor compliance or moderate to severe anaemia 7. FIGO adds that in severe anaemia, a haemoglobin below 7 g/dL, in the second or third trimester, "IV iron should be administered", and that when iron deficiency anaemia is found at the beginning of the third trimester, intravenous iron "should be considered" 7.

Before surgery

In Case 4, the patient has absolute iron deficiency, anaemia, a known cause and four weeks. The reference document for this situation is the 2017 international consensus statement on peri-operative anaemia and iron deficiency 8. It is distinct from the earlier NATA consensus on pre-operative anaemia 34.

The consensus diagnoses iron deficiency by the bands set out under Transferrin saturation and inflammation. Separately, it uses a ferritin below 100 µg/L as a trigger to treat low iron stores before surgery where moderate-to-high blood loss is expected 8. That figure is a treatment trigger, not a diagnostic cut-off; it says when to give iron before an operation, not who is iron deficient. The consensus sets a pre-operative haemoglobin target of at least 130 g/L (13.0 g/dL) for both men and women 8. A single target for both sexes is a choice the consensus makes; it is not the same as the sex-specific thresholds used to define anaemia.

On route, the consensus offers oral iron when surgery is six to eight weeks or more away, and intravenous iron when oral iron is not tolerated, is contraindicated or has failed, or when surgery is less than six weeks away 8. In Case 4 the interval is four weeks, so the consensus points to intravenous iron. His cause is already known. In a patient whose cause is not yet found, BSG 2021 recommends that iron replacement should not be deferred while awaiting investigations unless colonoscopy is imminent 6. The consensus puts the maximal haemoglobin response at about three weeks after intravenous iron 8, so a dose given at a pre-assessment visit a week before theatre has little time to act.

Raising the haemoglobin is not the same as improving the outcome. PREVENTT, a randomised, double-blind, controlled trial of intravenous ferric carboxymaltose before major abdominal surgery (Richards and colleagues, Lancet 2020), found no significant difference on its primary endpoint, the composite of blood transfusion or death, even though iron raised haemoglobin 35. In PREVENTT, 1,000 mg of ferric carboxymaltose was given 10–42 days before surgery; the composite of blood transfusion or death by 30 days occurred in 28% of the placebo group and 29% of the iron group (risk ratio 1.03, 95% CI 0.78–1.37) 35. Readmissions to hospital in the first 8 weeks after surgery, a secondary endpoint, were fewer with iron than with placebo: 13% against 22% (risk ratio 0.61, 95% CI 0.40–0.91) 35. This is a real limit on the case for pre-operative intravenous iron. PREVENTT tested whether iron changes surgical outcomes. It did not test whether iron deficiency anaemia should be treated, which BSG and the peri-operative consensus both recommend 6,8; the man in Case 4 is iron deficient and anaemic in his own right.

Pre-operative iron is one part of patient blood management, which also covers bleeding during surgery and the threshold for transfusion. A programme-wide report from Western Australia gives the scale of the effect: across 605,046 patients, units transfused per admission fell by 41%, with an odds ratio for mortality of 0.72 (95% CI 0.67–0.77) and an incidence rate ratio for length of stay of 0.85 36. A study of implementers in several countries placed Saudi Arabia at the initiation stage of adoption, driven by individual hospitals rather than a national programme, on interviews with four Saudi implementers 37. There is no published outcomes study of a Saudi programme.

Heavy menstrual bleeding and bleeding disorders

In Case 2, heavy periods since menarche come with nosebleeds, bleeding after a dental extraction and a sister with the same periods, and together they raise the question of a bleeding disorder. The link between heavy menstrual bleeding, iron deficiency and iron deficiency anaemia is the subject of Munro's 2023 review 38. FIGO's 2023 statement asks that heavy menstrual bleeding be actively investigated and treated when iron deficiency is found 7.

Iron deficiency is common in this group. A 2025 study found that 66% of women with von Willebrand disease had heavy menstrual bleeding, and that among menstruating women with heavy bleeding, 62% had a ferritin below 30 µg/L and 31% a haemoglobin below 12 g/dL 39.

The menstrual history matters in every woman with iron deficiency, including the student in Case 1, whose periods she did not think heavy. FIGO notes that heavy menstrual bleeding "is often normalised by society, HCPs and even the patient and their family" 7, a point Munro's review also makes 38. Two published tools give the history structure. The pictorial blood loss assessment chart (PBAC) measures the amount of bleeding, and a score above 100 defines heavy bleeding 40. The ISTH bleeding assessment tool screens for a bleeding disorder; it scores 14 bleeding domains, each from 0 to 4 41. The PBAC cut-off of 100 is a convention: it is where the chart's authors drew the line, not a point where physiology changes. The woman in Case 2 scores above 100 on the PBAC, and her history reaches several ISTH-BAT domains: heavy periods from menarche, nosebleeds needing packing, bleeding after a dental extraction, and a sister with the same history. A positive screen goes to formal haemostasis testing. ACOG's committee opinion on adolescents with heavy menstrual bleeding recommends obtaining a serum ferritin routinely in every adolescent who presents with it 42.

Treating the bleeding and treating the iron deficiency are two tasks. The bleeding belongs to the gynaecologist and, where a disorder is confirmed, to the haemostasis service. The iron deficiency is treated while the bleeding is investigated. BSG 2021 recommends that iron replacement "should not be deferred while awaiting investigations for IDA unless colonoscopy is imminent" (strong recommendation, high-quality evidence), and allows treatment to be delayed if colonoscopy is within 2 weeks 6. On route, one randomised trial addresses this setting directly: in women with iron deficiency anaemia from heavy uterine bleeding, ferric carboxymaltose raised haemoglobin by at least 2.0 g/dL in 82% of patients against 62% with oral ferrous sulphate (p<0.001) 43. If the bleeding is not controlled, the deficiency returns, and the ferritin is the measure that shows it.

Diet

In Case 1, the student has two causes, not one. A study of 250 non-pregnant women in Riyadh found a low haemoglobin in 28.4%, and a mean dietary iron intake of 2.28 mg a day against a requirement of 8.10 mg a day; anaemia was associated with both menstrual pattern and nutritional inadequacy 44. Haem iron is absorbed better than non-haem iron: 15–35% against 2–20%. Yet a 2024 analysis found no significant difference between the two in women of reproductive age, on evidence of very low certainty 45.

No study measures diet and menstrual loss together as a single cause; the link is reasoning, not a trial result. Menstruation takes iron out every month. A diet that supplies well under the requirement leaves no margin to replace it, so a loss that would be tolerated on a good diet becomes a deficit on a poor one. The deficiency itself is replaced as in any other patient. The diet matters for what happens afterwards: if neither cause changes, the ferritin will fall again.

Iron deficiency without anaemia

FIGO describes anaemia as a late sign of iron deficiency 7.

BSG 2021 gives the question its own section 6. Its statement 9 holds that the cancer risk in iron deficiency without anaemia is low (high-quality evidence, 92% consensus, strong recommendation). Its statement 22 finds insufficient evidence to support invasive investigation in non-anaemic iron deficiency unless there are other indications, and suggests periodic monitoring of the blood count instead (low-quality evidence, 92% consensus, weak recommendation). It adds that the threshold for investigation should be low in men, in postmenopausal women, and in those with gastrointestinal symptoms or a relevant family history. On treatment, BSG calls the efficacy of iron replacement unclear. It cites a meta-analysis that found no objective physiological benefit, measured by maximal oxygen uptake, respiratory exchange ratio or maximal heart rate, and it notes evidence of subjective improvement in fatigue, mental quality of life and cognitive function in premenopausal women. It concludes that "given the safety of the available iron preparations, it would be reasonable to offer treatment for NAID if symptomatic" 6.

Four randomised trials test treatment in non-anaemic iron deficiency. In 198 menstruating women with a haemoglobin of at least 12.0 g/dL and a ferritin below 50 µg/L, twelve weeks of oral iron reduced the fatigue score by 47.7%, against 28.8% with placebo; the difference between groups was 3.5 points (95% CI 0.3–6.7; p=0.02), with no effect on anxiety, depression or overall quality of life 46. In 90 premenopausal women with fatigue and a low ferritin, 800 mg of intravenous iron was compared with placebo; in those with a baseline ferritin of 15 µg/L or less, the trial reports a fall in fatigue score of 1.8 with iron against 0.4 with placebo (p=0.005), and more adverse events with iron (21% against 7%), none of them serious 47. The PREFER trial gave a single dose of ferric carboxymaltose to fatigued, iron-deficient women with a haemoglobin of at least 11.5 g/dL; it reports a reduction in fatigue of at least one point by day 56 in 65.3%, against 52.7% with placebo (p=0.03) 48.

The fourth trial was negative. In repeat blood donors with a ferritin of 50 µg/L or less and no anaemia, 800 mg of ferric carboxymaltose corrected ferritin and haemoglobin but made no difference to self-rated fatigue at 6–8 weeks (3.9 ± 1.8 with iron, 4.0 ± 2.2 with placebo; p=0.813) 49. Those donors were not selected for fatigue, whereas the women in the three positive trials were. The trials therefore show subjective benefit in symptomatic women and no benefit in one unselected group, and the meta-analysis cited by BSG found no objective physiological gain 6.

Correcting non-anaemic iron deficiency before surgery has been the subject of a published exchange of letters following the 2017 peri-operative consensus 50. In heart failure, the ESC defines iron deficiency by ferritin and TSAT alone, without reference to anaemia, and treats it with intravenous iron 12.

Children and adolescents

The American Academy of Pediatrics published a new clinical report on iron deficiency and iron deficiency anaemia in infants, children and adolescents in June 2026, replacing its report of 2010 51. The report's key recommendation is universal screening with a full blood count and ferritin at 9–12 months in infants who are mainly breastfed, or at 15–18 months in formula-fed infants after the change to cow's milk, with rescreening by risk up to the age of 4 years 51. ASH's 2026 guideline sets the ferritin threshold for children aged 9 months to 4 years at 20 µg/L or less 10. WHO's 2024 revision lowers the anaemia threshold for children aged 6–23 months to a haemoglobin below 10.5 g/dL, down from 11.0 g/dL; it leaves the threshold unchanged at 11.0 g/dL for children aged 24–59 months and at 11.5 g/dL for children aged 5–11 years 52.

Saudi paediatric data are limited. A retrospective review of 498 children aged 7 months to 17 years at a private hospital group in Riyadh found iron deficiency anaemia, defined as haemoglobin below 11 g/dL with ferritin below 10 µg/L, in 9.2% 53. Prevalence was highest in infants (16.9%) and fell with age: 12.0% in toddlers, 7.2% in preschool children and 0.8% in school-age children. Of the affected children, 72.3% had mild and 27.7% moderate anaemia; none had severe anaemia 53. These are hospital records from one city, not a population survey.

In adolescent girls, menarche brings menstrual loss. FIGO's statement applies from menarche onward and recommends assessing iron status with ferritin and/or TSAT 7. ASH places heavy menstrual bleeding among the high-risk groups for which the ferritin threshold is 50 µg/L or less 10. ACOG Committee Opinion 785 reports that a bleeding disorder is found in about 20% of adolescent girls who present for evaluation of heavy menstrual bleeding and in 33% of those hospitalised for it, and it recommends measuring serum ferritin routinely in adolescents who present with heavy menstrual bleeding 42.

The AAP report sets its ferritin threshold at 20 ng/mL or less in young and school-aged children and 30 ng/mL or less in adolescents and all menstruating individuals 51. On treatment it puts oral iron first: "In young children, initial therapy should consist of ferrous sulfate, 3 mg/kg elemental iron, administered once daily. In adolescents, initial therapy should consist of ferrous sulfate, 65 mg elemental iron, administered once daily" 51. It notes that "IV iron therapy is now far safer than it was several decades ago", but that its efficacy and safety data in children are limited to case series 51. Its potential indications for intravenous iron are persistent or refractory anaemia despite at least 3 months of oral iron; barriers to taking medication or to accessing care; ongoing losses, gastrointestinal or menstrual, where hormonal therapy fails or is not taken; anatomic causes such as bariatric or intestinal surgery, coeliac disease or inflammatory bowel disease; and inflammation with excess hepcidin 51. Children being considered for intravenous iron should usually be referred to a paediatric specialty centre 51.

In the United States, ferric carboxymaltose has been approved since December 2021 for iron deficiency anaemia in children from the age of 1 year who are intolerant of, or have not responded to, oral iron and have normal renal function; the labelled dose for children under 50 kg is 15 mg/kg per dose, given as two doses at least 7 days apart, to a maximum cumulative dose of 1,500 mg per course 54.

Safety of intravenous iron

Serious reactions to current intravenous iron products are uncommon. The trial figures for ferric carboxymaltose and ferric derisomaltose are given under Choosing a formulation. In the Veterans Health Administration cohort of 133,588 patients and 162,457 exposures, the overall rate of documented adverse reactions was 0.79%, and 0.63% were classed as potentially serious. Iron dextran had the highest rates in that cohort: 1.89% for any reaction, 1.53% for serious reactions and 0.36% for anaphylaxis 28.

Two larger analyses put numbers on the risk. A meta-analysis of 103 randomised trials, with 10,390 patients given intravenous iron, found no increase in serious adverse events against all comparators (relative risk 1.04, 95% CI 0.93–1.17) or against oral iron (relative risk 1.13, 95% CI 0.95–1.35) 61. Severe infusion reactions were more frequent with intravenous iron (relative risk 2.47, 95% CI 1.43–4.28; number needed to harm 292). There were 35 such reactions in 9,223 patients, none fatal, and no trial reported anaphylaxis or death 61. In the obstetric and gynaecological trials, serious adverse events were more frequent with intravenous iron (relative risk 2.00, 95% CI 1.15–3.62) 61. Eighty per cent of the trials had no valid grading of adverse events 61. In US Medicare data on 688,183 new users between 2003 and 2013, anaphylaxis at first exposure occurred in 68 per 100,000 with iron dextran and in 24 per 100,000 with the non-dextran products combined (iron sucrose, ferric gluconate and ferumoxytol), an adjusted odds ratio of 2.6 (95% CI 2.0–3.3) 62. Ferric carboxymaltose and ferric derisomaltose were not studied 62.

Most acute reactions are not allergic in the classical sense. Rampton and colleagues state: "CARPA may be the most common mechanism of acute HSRs provoked by any infusion containing nanoparticles, of which all existing IV iron preparations consist... There are, however, no data to support the concept that IgE-mediated hypersensitivity commonly accounts for reactions to current formulations of IV iron" 55. CARPA is complement activation-related pseudo-allergy.

A separate, minor reaction is often called the Fishbane reaction. The name comes from a 1996 safety series of 573 haemodialysis patients given iron dextran, in which 27 (4.7%) had an adverse reaction and 4 (0.7%) had a serious one 56. The paper does not itself use the eponym. The reaction is transient flushing, chest or back tightness and myalgia, without hypotension, wheeze or stridor. Auerbach and Macdougall attribute these minor reactions to the release of labile iron into the plasma, and note a normal tryptase 57. They settle without treatment. The risk lies in treating them as anaphylaxis: "unnecessary intervention with pressors or antihistamines can turn these minor symptoms into haemodynamically significant serious adverse events" 57.

The EMA no longer recommends a test dose, and asks instead for caution "with every dose of intravenous iron that is given, even if previous administrations have been well tolerated" 30. Rampton and colleagues give the reason: "No test dose of IV iron is necessary, because it can give false reassurance" 55.

Premedication with an antihistamine carries its own risks. Diphenhydramine can itself cause somnolence, sweating, hypotension and tachycardia. In a prospective study of 285 patients given iron dextran, antihistamine premedication accounted for most of the adverse events that had been attributed to the iron 57. Rampton and colleagues make the same point: H1 antagonists can make a reaction look more haemodynamically significant than it is 55.

Hypophosphataemia is the main non-allergic adverse effect that differs between products. It is common after ferric carboxymaltose and uncommon after ferric derisomaltose 26; the figures are in Choosing a formulation. The US label for ferric carboxymaltose carries a boxed warning for symptomatic hypophosphataemia: "INJECTAFER can cause severe, prolonged hypophosphatemia associated with serious outcomes, including hospitalization, osteomalacia and fractures requiring clinical intervention" 54. It adds that "Hypophosphatemia has occurred in patients with normal baseline phosphate levels and without apparent risk factors" 54. The UK summary of product characteristics reports, from the post-marketing setting, "Symptomatic hypophosphataemia leading to osteomalacia and fractures requiring clinical intervention including surgery" 23. According to the AAP report, low-molecular-weight iron dextran and ferumoxytol also carry boxed warnings 51.

Management of infusion reactions

Table 3 and Figure 2 follow the Rampton grading 55, with the minor Fishbane-type reaction described by Auerbach and Macdougall as a separate first step 57. The first task at the bedside is to tell the two apart. A minor reaction needs no drugs. A true hypersensitivity reaction needs to be graded and treated. The objective signs decide it: hypotension, wheeze or stridor move a reaction out of the minor category, and the grade then sets the response (Table 3, Figure 2).

Table 3 · Grading and management of acute reactions to intravenous iron

GradeFeaturesAction
Fishbane-type (minor, non-allergic)Transient flushing, chest or back tightness, myalgia. No hypotension, wheeze or stridorNo drugs; no antihistamine, no pressor. Symptoms settle on their own; resume once they have abated 57
Mild hypersensitivityMore subjective than objectiveStop the infusion for at least 15 minutes and assess. If improving, resume after 15 minutes at no more than 50% of the initial rate. If not resolved in 5–10 minutes, or worsening, treat as moderate 55
Moderate hypersensitivityTransient cough is a common first feature; more marked chest tightness or shortness of breath, with or without tachycardia or hypotensionStop immediately. Give isotonic fluid, for example 500 mL of 0.9% saline. IV hydrocortisone 100–500 mg can be considered. Monitor for at least 1 hour if improving 55
Severe, life-threatening (anaphylaxis)Increasing wheeze or bronchospasm, with or without stridor or laryngeal oedema, progressing to loss of consciousness, shock, or cardiac or respiratory arrestStop. Adrenaline: 0.1 mg IV (1 mL of 1:10,000) over 5 minutes in a monitored setting, or 0.3–0.5 mg IM (1:1000) into the anterolateral thigh. High-flow oxygen above 10 L/min. Rapid volume load, 1–2 L of 0.9% saline. Observe for at least 4 hours, and up to 24 hours if needed 55

Grades and actions follow Rampton et al. 2014; the Fishbane-type row follows Auerbach and Macdougall 2014. Every patient is observed for at least 30 minutes after each dose, whether or not a reaction occurs 30.

For adrenaline, the World Allergy Organization's 2020 guidance gives a weight-based IM dose of 0.01 mg/kg, to a maximum of 0.5 mg, repeated every 5–15 minutes if the response is inadequate. For cardiovascular instability it advises a fluid bolus of 20 mL/kg of crystalloid 58. The WAO guidance does not itself give an infusion rate for refractory anaphylaxis 58. Resuscitation Council UK's 2021 guidance gives 500 micrograms IM for adults and children aged 12 and over, repeated after 5 minutes if there is no improvement, and, for anaphylaxis that persists after two IM doses, a low-dose intravenous adrenaline infusion — 1 mg made up in 100 mL, starting at 0.5 mL/kg/h, about 0.1 µg/kg/min, and titrated to blood pressure 59.

In a published series of patients who had reacted to intravenous iron, recommencing the same infusion was tolerated in all 33 Fishbane-type, mild or moderate reactions, and rechallenge with an alternative product was tolerated in 68 of 69 reactions across all grades, including all 3 severe reactions 60.

Managing an acute reaction to intravenous iron Flow chart. Start the infusion with no test dose and no routine antihistamine. If there are no symptoms, observe for at least 30 minutes. If there are symptoms, classify the reaction as Fishbane-type, mild, moderate or severe, and act by grade: no drugs for Fishbane-type; stop and resume at half rate for mild; stop, fluids and consider hydrocortisone for moderate; stop, adrenaline, oxygen and fluids for severe. Observation then follows by grade. Start the infusion No test dose · no routine antihistamine Symptoms? No Yes: classify Observe at least 30 min after the dose Fishbane-type Flushing, chest or back tightness, myalgia; no low BP, wheeze or stridor Mild More subjective than objective Moderate Cough, chest tightness, short of breath ± fast pulse, low BP Severe Wheeze, stridor, laryngeal oedema, shock, collapse (anaphylaxis) No drugs No antihistamine, no pressor Settles on its own; resume once symptoms abate Stop ≥15 min Improving: resume at ≤50% of the initial rate Not settled in 5–10 min, or worse: treat as moderate Stop 500 mL 0.9% saline Consider IV hydrocortisone 100–500 mg Stop Adrenaline IM 0.3–0.5 mg (1:1000), or IV 0.1 mg over 5 min if monitored Oxygen >10 L/min 0.9% saline 1–2 L Observation At least 30 min after every dose · at least 1 h after a moderate reaction At least 4 h, up to 24 h, after anaphylaxis
Figure 2 · Managing an acute reaction to intravenous iron. Grades and actions follow Rampton et al. 55; the Fishbane-type branch follows Auerbach and Macdougall 57; the 30-minute observation after every dose is the EMA requirement 30. Adrenaline doses are for adults; the weight-based IM dose is 0.01 mg/kg, to a maximum of 0.5 mg 58.

Follow-up

The response to intravenous iron has a known time course. The 2017 international consensus reports that about half of the haemoglobin response is seen by day 5, about three-quarters by days 10–14, and the maximum at about three weeks after the dose 8. The response is judged against that timeline, so a haemoglobin checked too early is not read as a failure.

How long to follow a patient, and what counts as full repletion, is not settled. BSG 2021 states that "the duration required and indeed the appropriate measure of true iron repletion are both unclear", and it sets no numeric ferritin target 6. The ferritin cut-offs in the diagnostic guidelines are thresholds for diagnosis; ASH's 2026 figure of 50 ng/mL (50 µg/L) for high-risk groups, for example, is a diagnostic threshold and not a treatment target 10.

After ferric carboxymaltose, phosphate deserves attention at follow-up. In PHOSPHARE-IDA, three in four patients given that product had a serum phosphate below 2.0 mg/dL 26. The labels set out when to measure it. The UK summary of product characteristics asks for serum phosphate to be monitored in patients who receive multiple administrations at higher doses or long-term treatment, and in those with existing risk factors for hypophosphataemia, and for treatment to be re-evaluated if hypophosphataemia persists 23. The US label asks for serum phosphate to be checked before a repeat course in patients at risk of a low phosphate and in any patient who receives a repeat course within three months, and for pre-existing hypophosphataemia to be corrected before the dose 54.

If the cause persists, so does the loss. Follow-up is also the point at which to confirm that the cause has been treated.

Anaemia of inflammation

Anaemia of inflammation is a separate subject and outside this article. It meets iron deficiency in the functional-deficiency and sequestration bands of the 2017 consensus, described under Transferrin saturation and inflammation 8.

Conclusion

Iron deficiency is diagnosed from serum ferritin, read with TSAT when inflammation is present. The ferritin thresholds differ between guidelines, and each is a convention rather than a fact of biology. The diagnosis is not complete until the cause is known. At altitude, WHO's 2024 guideline raises the haemoglobin threshold for anaemia, by 1.4 g/dL at 2,000–2,499 m; WHO's 2020 ferritin guideline does not address altitude. Most guidelines recommend oral iron first: BSG 2021 and FIGO 2023, and the peri-operative consensus when surgery is six to eight weeks or more away. Intravenous iron comes first in heart failure and in active inflammatory bowel disease, and is used elsewhere for intolerance, failure, urgency and surgery less than six weeks away. It raises haemoglobin more than oral iron, by a modest margin and on low-certainty evidence. BSG regards treating symptomatic iron deficiency without anaemia as reasonable. In pregnancy, FIGO does not advise parenteral iron in the first trimester, and the iron sucrose labels report no data for that period. Two meta-analyses in pregnancy, neither with a first-trimester estimate, agree that intravenous iron raises haemoglobin more than oral iron and disagree on transfusion. Before surgery, intravenous iron raised haemoglobin in PREVENTT but did not reduce transfusion or death. Serious reactions to current products are uncommon, severe infusion reactions are more frequent than with oral iron, and the US label for ferric carboxymaltose carries a boxed warning for symptomatic hypophosphataemia. The personal note below sets out where the author's practice departs from these recommendations.

Personal note

I do not use oral iron. In my practice it is of historical interest only, and I treat iron deficiency with intravenous iron. My objection to oral iron is not the risk to the gut microbiota. The first reason is convenience. Most patients do not tolerate it, and those who do cannot be expected to stay on it for ever.

Oral iron would be the logical choice if the deficiency came from the diet. Here it does not: the local diet is rich in iron. It is blood loss that causes most iron deficiency, and oral iron cannot keep pace with losses that are still going on. The fear that keeps intravenous iron from being used is not grounded in science. In my view it is a myth.

I investigate and treat iron deficiency without anaemia in the same way as iron deficiency anaemia. I take a ferritin below 20 µg/L as the cut-off, and I aim for a ferritin above 50 µg/L after treatment. BSG 2021 sets no repletion target, and ASH 2026 uses a ferritin of 30 µg/L or less for most adults.

I do not use the Ganzoni formula. The haemoglobin and the patient's weight are enough to set the dose, and the products come with their own dosing tables built on those two values 23,24.

In Abha, at about 2,270 m, I define anaemia at a haemoglobin 0.5 g/dL above the sea-level threshold, for men and women alike. WHO 2024 adds 1.4 g/dL at 2,000–2,499 m, so my adjustment is smaller. Altitude changes nothing about the ferritin threshold.

In the first trimester of pregnancy, iron sucrose (Ferosac) is acceptable to me. FIGO 2023 does not advise parenteral iron in the first trimester, and the product labels report an absence of data for this period.

When there is no dedicated infusion unit, I give intravenous iron in the clinic itself, and I consider that the better arrangement.

Anaemia of inflammation is a separate topic. There too I give intravenous iron.

Disclosure and attribution

I have no conflicts of interest to declare. This article was researched and drafted with the help of AI. Every reference was checked against its PubMed record or the publisher's or regulator's own document. It is written for clinicians and is not a substitute for a guideline, a specialist opinion, or the judgement of the physician treating the patient.

References

  1. Camaschella C. Iron deficiency. Blood 2019; 133: 30–39. doi:10.1182/blood-2018-05-815944 PMID 30401704
  2. Owaidah T, Al-Numair N, Al-Suliman A, et al. Iron Deficiency and Iron Deficiency Anemia Are Common Epidemiological Conditions in Saudi Arabia: Report of the National Epidemiological Survey. Anemia 2020; 2020: 6642568. doi:10.1155/2020/6642568 PMID 33936813
  3. Algahtani FH, Ezzat HM, Alabdulaali MK, et al. Anemia and Iron Deficiency Anemia in Saudi Arabia: A Systematic Review of Prevalence and Contributing Factors. J Clin Med 2026; 15: 6074. doi:10.3390/jcm15156074 PMID 42590176
  4. Radhwi OO, Raslan OM, Almoshary MA, et al. Unmasking iron deficiency and iron deficiency anemia in Saudi Arabia: data from a large private-sector lab. Saudi Med J 2025; 46: 1000–1007. doi:10.15537/smj.2025.46.9.20240970 PMID 40897424
  5. Alkhaldy HY, Hadi RA, Alghamdi KA, et al. The pattern of iron deficiency with and without anemia among medical college girl students in high altitude southern Saudi Arabia. J Fam Med Prim Care 2020; 9: 5018–5025. doi:10.4103/jfmpc.jfmpc_730_20 PMID 33209838
  6. Snook J, Bhala N, Beales ILP, et al. British Society of Gastroenterology guidelines for the management of iron deficiency anaemia in adults. Gut 2021; 70: 2030–2051. doi:10.1136/gutjnl-2021-325210 PMID 34497146
  7. International Federation of Gynecology and Obstetrics. FIGO Statement: "Iron deficiency and anaemia in women and girls." 12 September 2023. https://www.figo.org/resources/figo-statements/iron-deficiency-and-anaemia-women-and-girls
  8. Muñoz M, Acheson AG, Auerbach M, et al. International consensus statement on the peri-operative management of anaemia and iron deficiency. Anaesthesia 2017; 72: 233–247. doi:10.1111/anae.13773 PMID 27996086
  9. Rockey DC, Altayar O, Falck-Ytter Y, et al. AGA Technical Review on Gastrointestinal Evaluation of Iron Deficiency Anemia. Gastroenterology 2020; 159: 1097–1119. doi:10.1053/j.gastro.2020.06.045 PMID 32828801
  10. Powers JM, Lim MY, Achebe MO, et al. American Society of Hematology 2026 guidelines for diagnosis of iron deficiency. Blood Adv 2026 (published online ahead of print). doi:10.1182/bloodadvances.2025015950 PMID 42747316
  11. Ko CW, Siddique SM, Patel A, et al. AGA Clinical Practice Guidelines on the Gastrointestinal Evaluation of Iron Deficiency Anemia. Gastroenterology 2020; 159: 1085–1094. doi:10.1053/j.gastro.2020.06.046 PMID 32810434
  12. McDonagh TA, Metra M, Adamo M, et al. 2023 Focused Update of the 2021 ESC Guidelines for the diagnosis and treatment of acute and chronic heart failure. Eur Heart J 2023; 44: 3627–3639. doi:10.1093/eurheartj/ehad195 PMID 37622666
  13. 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; 9: 211–222. doi:10.1093/ecco-jcc/jju009 PMID 25518052
  14. Hershko C, Camaschella C. How I treat unexplained refractory iron deficiency anemia. Blood 2014; 123: 326–333. doi:10.1182/blood-2013-10-512624 PMID 24215034
  15. World Health Organization. "Guideline on haemoglobin cutoffs to define anaemia in individuals and populations." Geneva: WHO, 5 March 2024. https://iris.who.int/handle/10665/376196
  16. Paganini D, Uyoga MA, Zimmermann MB. Iron Fortification of Foods for Infants and Children in Low-Income Countries: Effects on the Gut Microbiome, Gut Inflammation, and Diarrhea. Nutrients 2016; 8: 494. doi:10.3390/nu8080494 PMID 27529276
  17. Tolkien Z, Stecher L, Mander AP, et al. Ferrous sulfate supplementation causes significant gastrointestinal side-effects in adults: a systematic review and meta-analysis. PLoS One 2015; 10: e0117383. doi:10.1371/journal.pone.0117383 PMID 25700159
  18. 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; 126: 1981–1989. doi:10.1182/blood-2015-05-642223 PMID 26289639
  19. 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; 4: e524–e533. doi:10.1016/S2352-3026(17)30182-5 PMID 29032957
  20. 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; 396: 1895–1904. doi:10.1016/S0140-6736(20)32339-4 PMID 33197395
  21. 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; 400: 2199–2209. doi:10.1016/S0140-6736(22)02083-9 PMID 36347265
  22. Macdougall IC, White C, Anker SD, et al. Intravenous Iron in Patients Undergoing Maintenance Hemodialysis. N Engl J Med 2019; 380: 447–458. doi:10.1056/NEJMoa1810742 PMID 30365356
  23. Ferinject (ferric carboxymaltose 50 mg iron/mL), Vifor France. Summary of Product Characteristics, revised 22 May 2025. https://www.medicines.org.uk/emc/product/5910/smpc
  24. Monofer (ferric derisomaltose), Pharmacosmos UK Limited. Summary of Product Characteristics, last updated 28 March 2025. https://www.medicines.org.uk/emc/product/5676/smpc
  25. Venofer (iron sucrose), Vifor Pharma UK Limited. Summary of Product Characteristics, last revised 13 December 2021. https://www.medicines.org.uk/emc/product/5911/smpc
  26. Wolf M, Rubin J, Achebe M, et al. Effects of Iron Isomaltoside vs Ferric Carboxymaltose on Hypophosphatemia in Iron-Deficiency Anemia: Two Randomized Clinical Trials. JAMA 2020; 323: 432–443. doi:10.1001/jama.2019.22450 PMID 32016310
  27. Kennedy NA, Achebe MM, Biggar P, et al. A systematic literature review and meta-analysis of the incidence of serious or severe hypersensitivity reactions after administration of ferric derisomaltose or ferric carboxymaltose. Int J Clin Pharm 2023; 45: 604–612. doi:10.1007/s11096-023-01548-2 PMID 37010731
  28. Khalaf A, Lane M, Reid JM. Documented Adverse Reactions to Different Intravenous Iron Formulations in the Veterans Health Administration: A 10-Year Retrospective Study. Pharmacoepidemiol Drug Saf 2026; 35: e70411. doi:10.1002/pds.70411 PMID 42289295
  29. Wolf M, Auerbach M, Kalra PA, et al. Safety of ferric derisomaltose and iron sucrose in patients with iron deficiency anemia: the FERWON-IDA/NEPHRO trials. Am J Hematol 2021; 96: E11–E15. doi:10.1002/ajh.26015 PMID 33027541
  30. European Medicines Agency, Committee for Medicinal Products for Human Use. "New recommendations to manage risk of allergic reactions with intravenous iron-containing medicines." 28 June 2013, EMA/377372/2013. https://www.ema.europa.eu/en/news/new-recommendations-manage-risk-allergic-reactions-intravenous-iron-containing-medicines
  31. Venofer (iron sucrose injection), American Regent, Inc. US Prescribing Information. https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=626dc9e5-c6b4-4f9c-9bf4-774fd3ae619a
  32. Ferosac (iron sucrose), SPIMACO Addwaeih. Package leaflet, Saudi Food and Drug Authority drug directory. https://sdi.sfda.gov.sa/home/Result?drugId=4728
  33. Derman RJ, Bellad MB, Somannavar MS, et al. Single-dose intravenous iron vs oral iron for treatment of maternal iron deficiency anemia: a randomized clinical trial. Am J Obstet Gynecol 2025; 233: 120.e1–120.e18. doi:10.1016/j.ajog.2025.01.037 PMID 39909327
  34. Goodnough LT, Maniatis A, Earnshaw P, et al. Detection, evaluation, and management of preoperative anaemia in the elective orthopaedic surgical patient: NATA guidelines. Br J Anaesth 2011; 106: 13–22. doi:10.1093/bja/aeq361 PMID 21148637
  35. Richards T, Baikady RR, Clevenger B, et al. Preoperative intravenous iron to treat anaemia before major abdominal surgery (PREVENTT): a randomised, double-blind, controlled trial. Lancet 2020; 396: 1353–1361. doi:10.1016/S0140-6736(20)31539-7 PMID 32896294
  36. Leahy MF, Hofmann A, Towler S, et al. Improved outcomes and reduced costs associated with a health-system-wide patient blood management program: a retrospective observational study in four major adult tertiary-care hospitals. Transfusion 2017; 57: 1347–1358. doi:10.1111/trf.14006 PMID 28150313
  37. Hofmann A, Spahn DR, Holtorf AP; PBM Implementation Group. Making patient blood management the new norm(al) as experienced by implementors in diverse countries. BMC Health Serv Res 2021; 21: 634. doi:10.1186/s12913-021-06484-3 PMID 34215251
  38. Munro MG. Heavy menstrual bleeding, iron deficiency, and iron deficiency anemia: framing the issue. Int J Gynaecol Obstet 2023; 162(Suppl 2): 7–13. doi:10.1002/ijgo.14943 PMID 37538011
  39. Myrin-Westesson L, Elfvinge P, Zetterberg E, et al. Prevalence of heavy menstrual bleeding, iron deficiency, iron deficiency anemia, and treatment in women with von Willebrand disease—a cohort study. Res Pract Thromb Haemost 2025; 9: 102949. doi:10.1016/j.rpth.2025.102949 PMID 40697484
  40. Higham JM, O'Brien PM, Shaw RW. Assessment of menstrual blood loss using a pictorial chart. Br J Obstet Gynaecol 1990; 97: 734–739. doi:10.1111/j.1471-0528.1990.tb16249.x PMID 2400752
  41. Rodeghiero F, Tosetto A, Abshire T, et al. ISTH/SSC bleeding assessment tool: a standardized questionnaire and a proposal for a new bleeding score for inherited bleeding disorders. J Thromb Haemost 2010; 8: 2063–2065. doi:10.1111/j.1538-7836.2010.03975.x PMID 20626619
  42. American College of Obstetricians and Gynecologists Committee on Adolescent Health Care. Screening and Management of Bleeding Disorders in Adolescents With Heavy Menstrual Bleeding: ACOG Committee Opinion No. 785. Obstet Gynecol 2019; 134: e71–e83. doi:10.1097/AOG.0000000000003411 PMID 31441825
  43. Van Wyck DB, Mangione A, Morrison J, et al. Large-dose intravenous ferric carboxymaltose injection for iron deficiency anemia in heavy uterine bleeding: a randomized, controlled trial. Transfusion 2009; 49: 2719–2728. doi:10.1111/j.1537-2995.2009.02327.x PMID 19682342
  44. AlFaris N, ALTamimi J, AlKehayez N, et al. Prevalence of Anemia and Associated Risk Factors Among Non-Pregnant Women in Riyadh, Saudi Arabia: A Cross-Sectional Study. Int J Gen Med 2021; 14: 765–777. doi:10.2147/IJGM.S299450 PMID 33707967
  45. Gallo Ruelas M, Alvarado-Gamarra G, Aramburu A, et al. A comparative analysis of heme vs non-heme iron administration: a systematic review and meta-analysis of randomized controlled trials. Eur J Nutr 2024; 64: 51. doi:10.1007/s00394-024-03564-y PMID 39708071
  46. Vaucher P, Druais PL, Waldvogel S, et al. Effect of iron supplementation on fatigue in nonanemic menstruating women with low ferritin: a randomized controlled trial. CMAJ 2012; 184: 1247–1254. doi:10.1503/cmaj.110950 PMID 22777991
  47. Krayenbuehl PA, Battegay E, Breymann C, et al. Intravenous iron for the treatment of fatigue in nonanemic, premenopausal women with low serum ferritin concentration. Blood 2011; 118: 3222–3227. doi:10.1182/blood-2011-04-346304 PMID 21705493
  48. Favrat B, Balck K, Breymann C, et al. Evaluation of a single dose of ferric carboxymaltose in fatigued, iron-deficient women: PREFER, a randomized, placebo-controlled study. PLoS One 2014; 9: e94217. doi:10.1371/journal.pone.0094217 PMID 24751822
  49. Keller P, von Känel R, Hincapié CA, et al. The effects of intravenous iron supplementation on fatigue and general health in non-anemic blood donors with iron deficiency. Sci Rep 2020; 10: 14219. doi:10.1038/s41598-020-71048-0 PMID 32848185
  50. Miles LF, Story DA, Litton E. Peri-operative correction of non-anaemic iron deficiency. Anaesthesia 2017; 72: 910–911. doi:10.1111/anae.13918 PMID 28608383
  51. Powers JM, Heeney MM, Hord J, et al. Prevention, Screening, Diagnosis, and Treatment of Iron Deficiency and Iron Deficiency Anemia in Infants, Children, and Adolescents: Clinical Report. Pediatrics 2026; 158: e2026077414. doi:10.1542/peds.2026-077414 PMID 42324084
  52. World Health Organization. "Guideline on haemoglobin cutoffs to define anaemia in individuals and populations." Geneva: WHO, 5 March 2024. https://iris.who.int/handle/10665/376196
  53. Almutairi AM, Alwehaibi SA, Almousa AY, et al. A Multicenter Retrospective Chart Review Study Estimating the Prevalence of Iron Deficiency Anemia Among Infants, Toddlers, and Children in Riyadh, Saudi Arabia. Cureus 2024; 16: e70031. doi:10.7759/cureus.70031 PMID 39449868
  54. Injectafer (ferric carboxymaltose injection), American Regent, Inc. US Prescribing Information, revised August 2026. https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=517b4a19-45b3-4286-9f6a-ced4e10447de
  55. Rampton D, Folkersen J, Fishbane S, et al. Hypersensitivity reactions to intravenous iron: guidance for risk minimization and management. Haematologica 2014; 99: 1671–1678. doi:10.3324/haematol.2014.111492 PMID 25420283
  56. Fishbane S, Ungureanu VD, Maesaka JK, et al. The safety of intravenous iron dextran in hemodialysis patients. Am J Kidney Dis 1996; 28: 529–534. doi:10.1016/S0272-6386(96)90463-1 PMID 8840942
  57. Auerbach M, Macdougall IC. Safety of intravenous iron formulations: facts and folklore. Blood Transfus 2014; 12: 296–300. doi:10.2450/2014.0094-14 PMID 25074787
  58. Cardona V, Ansotegui IJ, Ebisawa M, et al. World allergy organization anaphylaxis guidance 2020. World Allergy Organ J 2020; 13: 100472. doi:10.1016/j.waojou.2020.100472 PMID 33204386
  59. Working Group of Resuscitation Council UK. "Emergency treatment of anaphylaxis: Guidelines for healthcare providers." Resuscitation Council UK, May 2021 (review date May 2026). https://www.resus.org.uk/sites/default/files/2021-05/Emergency%20Treatment%20of%20Anaphylaxis%20May%202021_0.pdf
  60. Stojanovic S, Graudins LV, Aung AK, et al. Safety of Intravenous Iron Following Infusion Reactions. J Allergy Clin Immunol Pract 2021; 9: 1660–1666. doi:10.1016/j.jaip.2020.11.028 PMID 33248279
  61. Avni T, Bieber A, Grossman A, Green H, Leibovici L, Gafter-Gvili A. The safety of intravenous iron preparations: systematic review and meta-analysis. Mayo Clin Proc 2015; 90: 12–23. doi:10.1016/j.mayocp.2014.10.007 PMID 25572192
  62. Wang C, Graham DJ, Kane RC, et al. Comparative risk of anaphylactic reactions associated with intravenous iron products. JAMA 2015; 314: 2062–2068. doi:10.1001/jama.2015.15572 PMID 26575062
  63. Gurusamy KS, Nagendran M, Broadhurst JF, Anker SD, Richards T. Iron therapy in anaemic adults without chronic kidney disease. Cochrane Database Syst Rev 2014; 2014(12): CD010640. doi:10.1002/14651858.CD010640.pub2 PMID 25550190
  64. Nicholson L, Axon E, Daru J, Rogozińska E. Effect and safety of intravenous iron compared to oral iron for treatment of iron deficiency anaemia in pregnancy. Cochrane Database Syst Rev 2024; 12: CD016136. doi:10.1002/14651858.CD016136 PMID 39651609
  65. Sales SK, Rajprohat S, Simon L, et al. Intravenous vs oral iron for treating iron deficiency anemia in pregnancy: a systematic review and meta-analysis. JAMA Netw Open 2026; 9: e2630657. doi:10.1001/jamanetworkopen.2026.30657 PMID 42776532
  66. World Health Organization. "WHO guideline on use of ferritin concentrations to assess iron status in individuals and populations." Geneva: WHO, 2020. https://iris.who.int/handle/10665/331505