Anaemia is rarely a diagnosis in itself — it is a sign of an underlying condition. Missing a GI malignancy behind iron-deficiency anaemia (IDA), or failing to recognise aplastic anaemia, has life-altering consequences. NICE NG12 mandates 2WW colorectal referral for unexplained IDA aged ≥60. Hb <70 g/L is associated with increased perioperative mortality and cardiac events; these patients need same-day input. Haemolysis can be life-threatening (e.g. TTP, haemolytic uraemic syndrome) and deteriorates rapidly without specialist treatment.

MCV is the single most useful discriminating parameter in anaemia workup. It narrows a broad differential to two or three diagnoses rapidly, avoiding unnecessary investigations. Reticulocyte count is systematically underused in primary care but is highly informative: a reticulocyte production index >2 indicates haemolysis or haemorrhage; <2 with anaemia indicates underproduction. Blood film adds morphological data (e.g. target cells in thalassaemia, hypersegmented neutrophils in B12 deficiency) that automated counters miss.

Ferritin is the single most useful confirmatory test for IDA but is an acute-phase reactant — it can be falsely elevated in inflammation. A ferritin <30 μg/L in the context of elevated CRP is still likely IDA. Coeliac serology (tTG-IgA) should be checked in all new IDA — prevalence of coeliac in IDA is ~5% and it is frequently missed. B12 and folate should always be checked together as folate supplementation can mask B12 deficiency and precipitate subacute combined degeneration of the cord. MDS is a diagnosis not to miss in the elderly with macrocytosis and no reversible cause.

Examination in anaemia is often cursory in primary care. Clinical signs frequently identify the cause (glossitis = B12/iron, koilonychia = IDA, splenomegaly = haemolysis or haematological malignancy) and influence the urgency of referral. PR examination is repeatedly deferred in IDA and is a patient-safety issue — rectal malignancy is missed this way. Neurological examination in B12 deficiency is critical because subacute combined degeneration of the cord can occur at Hb levels that are near normal; delaying treatment causes irreversible damage.

NICE NG12 mandates that unexplained IDA in adults aged ≥60 warrants 2WW colorectal referral — upper and lower GI endoscopy finds a cause in ~60% of these patients, with malignancy in ~10%. Coeliac serology is commonly overlooked: prevalence of coeliac in IDA is approximately 3–5% in UK adults. Parietal cell antibodies are positive in ~90% of pernicious anaemia but are not specific; intrinsic factor antibodies are less sensitive (~50%) but highly specific. Serum B12 alone can miss functional B12 deficiency — methylmalonic acid is a more sensitive marker of cellular B12 insufficiency.

NICE NG12 (2015, updated 2023) mandates 2WW colorectal referral for IDA in patients aged ≥60 — this applies even without overt GI symptoms. Studies show ~10% of these patients have colorectal malignancy. Failure to refer is a common cause of delayed cancer diagnosis complaints. Thalassaemia trait should be referred for genetic counselling, particularly for couples planning pregnancy (if both partners are carriers, 25% risk of thalassaemia major). IDA not responding to 3 months of adequate oral iron replacement must be escalated — causes include ongoing blood loss, malabsorption, and non-adherence.

Oral iron is absorbed best every other day (alternate-day dosing reduces hepcidin-mediated absorption block), though NICE CKS still recommends BD dosing in practice — consider QD or QOD if side-effects limit adherence. IV iron corrects IDA faster than oral (Hb normalises within 1–2 weeks vs 4 weeks orally) and is preferred in IBD (where oral iron worsens mucosal inflammation), CKD, and malabsorption. For B12: oral cyanocobalamin at 1000 mcg/day is equivalent to IM injections in patients without pernicious anaemia or malabsorption, but IM is preferred when certainty of absorption is needed. Folate supplementation without checking B12 is a patient safety error — the risk of precipitating or worsening subacute combined degeneration is well-documented.

Dietary modifications alone rarely cure established anaemia but significantly aid recovery and prevent recurrence. Vitamin C co-ingestion with iron-rich meals or supplements increases non-haem iron absorption by up to 300% — this is equivalent to doubling iron intake with no additional supplementation cost. In vegan patients, B12 supplementation prevents deficiency entirely and is far preferable to treating established neurological damage later. The LNG-IUS (Mirena coil) reduces menstrual blood loss by approximately 90% at 12 months and is the most effective non-surgical treatment for menorrhagia-associated IDA. Alcohol is a nutritional triple-threat in anaemia: it reduces folate absorption, impairs erythropoiesis directly, and causes GI haemorrhage.

Follow-up in anaemia serves three purposes: (1) confirm treatment response (Hb rising ≥10 g/L per month), (2) ensure the cause has been found and treated, and (3) detect complications early. IDA that fails to respond to oral iron after 3 months is an important clinical signal — non-adherence, ongoing blood loss, and malabsorption must all be addressed. Re-emerging IDA after treatment is common and often indicates inadequate investigation of the original cause. In B12 deficiency, neurological symptoms can progress even during treatment if the interval between injections is too long — patients with neurological involvement should be on 2-monthly injections, not 3-monthly.