Iron deficiency anaemia in a post-menopausal woman or a man of any age is a red flag that mandates gastrointestinal investigation, not dietary counselling — the BSG guidelines on investigation of iron deficiency anaemia are explicit: IDA in a post-menopausal woman or in a man has an approximately 15% chance of underlying GI malignancy (colorectal or gastric cancer). 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 approximately 10% 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 menorrhagia and normal diet = treat and monitor; any GI symptoms, family history CRC, or age approaching menopause = 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' (e.g., 50-100 mcg/L) 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: transferrin saturation below 20% + serum iron below 10 mcg/dl + elevated TIBC = iron deficiency even if ferritin appears normal. 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: transferrin saturation <20% + clinical context = iron deficiency regardless of ferritin level.

The Mentzer index (MCV divided by RBC count) is a quick bedside calculation that helps 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 (Goddard et al. 2011, updated regularly) states: 'Investigation with both upper and lower GI endoscopy should be arranged in all patients with IDA who are male or post-menopausal female. All pre-menopausal women and those with an obvious cause for blood loss (e.g., menorrhagia) should have further investigation if symptoms suggest GI pathology or if there is poor or no response to treatment.' The simultaneous bidirectional investigation principle: approximately 10% of patients with IDA who have a normal upper GI endoscopy have 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 — a single 1,000 mg IV infusion given over 15 minutes repletes iron stores completely in most patients and produces Hb responses of 15-25 g/L within 4 weeks. The main complication to monitor is hypophosphataemia — ferric carboxymaltose stimulates FGF23 (fibroblast growth factor 23), which reduces renal phosphate reabsorption. Serum phosphate should be checked 2-4 weeks after infusion — levels below 0.5 mmol/L require oral phosphate supplementation. Symptomatic hypophosphataemia (muscle weakness, bone pain, respiratory failure) occurs rarely but is a recognised complication. 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. Its efficacy is superior to all other medical treatments: it reduces menstrual blood loss by approximately 90% at 12 months (compared to approximately 50% for tranexamic acid and approximately 30-40% for combined OCP). 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 QDS during the menstrual period (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 (BALTAR trial) 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. Annual ferritin monitoring for patients who have had a single episode of IDA (with identified cause) allows early detection of recurrence before symptoms develop. In patients with unexplained IDA (no identified cause despite thorough investigation): capsule endoscopy via gastroenterology should be considered (detects small bowel angiodysplasia, Crohn, tumour) and annual ferritin monitoring is mandatory.