Iron deficiency anaemia in a post-menopausal woman or a man of any age is a red flag that generally warrants gastrointestinal investigation, not dietary counselling — the BSG guideline on iron deficiency anaemia (Snook et al, Gut 2021) recommends bidirectional investigation in men and post-menopausal women with unexplained IDA because of the risk of underlying GI malignancy, and states that FIT should not be used to exclude significant pathology in confirmed IDA. The investigation should be bidirectional (both upper and lower GI) because occult upper GI bleeding (gastric cancer, oesophageal cancer, gastric ulcer, oesophagitis with Cameron lesion in hiatus hernia) and lower GI bleeding (colorectal cancer, angiodysplasia, polyps) can both cause IDA. The practical guidance: OGD + colonoscopy or CT colonography should be arranged simultaneously (not sequentially) for these patients, as some have both upper and lower GI pathology. If only one investigation is performed and normal, the other must still be arranged. Pre-menopausal women with IDA (the most common group) — investigation is guided by symptoms: clear heavy menstrual bleeding and no red flags = treat and monitor; GI symptoms, family history of CRC, age approaching menopause, or anaemia that is disproportionate, recurrent, unexplained or refractory = investigate.

The coeliac disease-IDA connection is one of the most important and most frequently missed associations in primary care — coeliac disease damages the villous epithelium of the duodenum and proximal jejunum, which is the primary site of iron absorption (dietary iron is absorbed as Fe2+ in the duodenum via DMT1 transporter). In coeliac disease, villous atrophy dramatically reduces the absorptive surface area for iron, causing iron deficiency even when dietary iron intake is adequate. Approximately 5% of patients with IDA in primary care have coeliac disease as the cause. The critical clinical implication: anti-tTG IgA + total IgA should be checked in every patient with unexplained IDA, even without GI symptoms (silent coeliac is common). Starting a patient on iron supplementation without excluding coeliac disease means: (1) the iron may be poorly absorbed (wasted treatment); (2) the underlying cause remains undiagnosed; (3) if untreated coeliac disease is present, the patient continues to have GI inflammation and increased risk of complications (osteoporosis, lymphoma, infertility). The diagnosis is made on raised anti-tTG IgA + duodenal biopsy (Marsh 3 lesion) — GFD leads to villous recovery and iron absorption normalises within 3-6 months of strict adherence.

Ferritin interpretation in inflammatory disease is one of the most practically important clinical skills in interpreting iron studies — ferritin is an acute phase reactant that rises in response to inflammation, infection, malignancy, and liver disease. In a patient with rheumatoid arthritis, IBD, CKD, or any inflammatory condition, the ferritin may be 'normal' while the patient is actually iron-depleted (true iron stores are low, but the inflammatory stimulus has raised ferritin to a falsely reassuring level). In this context, the additional iron studies are essential for diagnosis: a low transferrin saturation supports iron deficiency even if ferritin appears normal (serum iron alone is subject to substantial diurnal and biological variation). The soluble transferrin receptor (sTfR) is the most sensitive marker for iron-deficient erythropoiesis in inflammatory conditions — it is elevated in iron deficiency but not affected by inflammation. The sTfR/log ferritin ratio (Thomas plot) is the gold standard for distinguishing IDA from anaemia of chronic disease, but is not widely available in primary care. In practice: interpret a normal or raised ferritin with CRP, transferrin saturation, red-cell indices, reticulocyte haemoglobin where available and the clinical context — in inflammatory disease, iron deficiency may coexist with anaemia of inflammation despite a non-low ferritin. There is no universal ferritin diagnostic threshold.

The Mentzer index (MCV divided by RBC count) is a quick screening aid — not a diagnostic test — that may help distinguish iron deficiency anaemia from thalassaemia trait — both conditions cause microcytic hypochromic anaemia and can be confused without further testing. The calculation: MCV (fl) / RBC count (x10^12/L). Result below 13 = thalassaemia trait likely (the RBC count is maintained or elevated because the bone marrow compensates for small cells by making more of them). Result above 13 = iron deficiency anaemia likely (the RBC count falls in proportion to the MCV). This index has a sensitivity and specificity of approximately 75-85% for distinguishing the two conditions — it should trigger haemoglobin electrophoresis (for beta-thalassaemia trait: HbA2 >3.5%) or referral for haematology in cases where the distinction matters (particularly for reproductive counselling in patients of South/Southeast Asian, Middle Eastern, or Mediterranean origin where thalassaemia trait prevalence is high).

The BSG guideline on iron deficiency anaemia (Snook et al, Gut 2021, replacing Goddard et al 2011) recommends bidirectional endoscopy (upper GI endoscopy plus colonoscopy or CT colonography) for men and post-menopausal women with IDA, and GI investigation in pre-menopausal women when there are GI symptoms, a strong family history of colorectal cancer, or IDA that persists despite treatment and correction of menstrual loss. The simultaneous bidirectional investigation principle: a normal upper GI endoscopy does not exclude a lower GI lesion, and vice versa — performing only one investigation misses these patients. GPs who refer for OGD only (assuming upper GI cause) and do not arrange colonoscopy are following an incomplete investigation pathway.

Ferric carboxymaltose (Ferinject) IV iron has transformed the management of significant iron deficiency anaemia — IV iron can replete stores rapidly, but the dose must be calculated using the product-specific method and local protocol. The main complication to monitor is hypophosphataemia — ferric carboxymaltose stimulates FGF23 (fibroblast growth factor 23), which reduces renal phosphate reabsorption. Hypophosphataemia can be severe and may cause osteomalacia and fractures, particularly with repeated or high-dose treatment. MHRA: monitor serum phosphate in patients receiving multiple high-dose administrations or long-term treatment and in those with pre-existing risk factors; re-evaluate treatment in persistent hypophosphataemia. The NHS 'Getting It Right First Time' (GIRFT) programme has recommended expansion of IV iron use in primary care for IDA in IBD, CKD, and pre-operative patients — many ICBs now have pathways for GP-initiated IV iron infusion in day units without specialist referral. GPs should check local pathways.

The levonorgestrel-releasing IUS (Mirena) for menorrhagia is one of the most evidence-based interventions in primary care gynaecology — the NICE NG88 (Heavy Menstrual Bleeding) guideline recommends the LNG-IUS as the first-line pharmacological treatment for menorrhagia without structural pathology. It is not suitable for every patient — the choice depends on fibroids, uterine cavity distortion, adenomyosis, contraception requirements and patient preference. The mechanism: progestogen-mediated endometrial atrophy reduces endometrial proliferation and vascularity. The additional contraceptive benefit is relevant for women seeking both menorrhagia treatment and contraception. For women who decline IUS: tranexamic acid 1 g TDS for up to 4 days during the menstrual period (BNF) (combined with mefenamic acid 500 mg TDS if dysmenorrhoea coexists) is the most effective non-hormonal option. The GP should document: menorrhagia managed, iron supplementation prescribed, follow-up planned to confirm Hb response, and IUS/hormonal management initiated or referral made for refractory cases.

The alternate-day iron dosing strategy (Stoffel et al, Lancet Haematology 2017) is an evidence-based approach that improves tolerability of oral iron supplementation without significantly compromising efficacy — the reason is hepcidin physiology. After each oral iron dose, the liver increases production of hepcidin (the master regulator of iron homeostasis), which blocks the ferroportin channel in duodenal enterocytes for approximately 24 hours, preventing further iron absorption. This means that twice-daily dosing results in partial inhibition of absorption for the second dose (taken when hepcidin is still elevated). By dosing every other day, hepcidin has time to fall back to baseline before the next dose, allowing maximum absorption. The practical advice: if a patient finds daily ferrous sulphate intolerable, alternating-day dosing is an evidence-based alternative that maintains adequate Hb response with significantly fewer GI side effects.

The recurrence of IDA as a safety-net principle is clinically important — a significant proportion of patients who are treated successfully for IDA relapse within 12-24 months, often because the underlying cause has not been adequately addressed. The most common reasons for IDA recurrence: ongoing unrecognised GI blood loss (particularly from angiodysplasia in elderly — missed on initial colonoscopy), suboptimal menorrhagia management (LNG-IUS removed, hormonal treatment discontinued), undiagnosed or inadequately treated coeliac disease (dietary compliance poor), and ongoing NSAID use. An individualised, documented follow-up plan allows early detection of recurrence. In recurrent or refractory IDA despite adequate-quality bidirectional endoscopy, refer to gastroenterology for small-bowel assessment (usually capsule endoscopy; detects small bowel angiodysplasia, Crohn, tumour) and consider renal-tract evaluation; any long-term iron should be documented and periodically reviewed.