Anaemia — Systematic Workup: Written Clinical Reasoning

SAQ 1 — Integrated Anaemia Workup and Management (20 marks, 30 minutes)

Prompt: Classify this patient's anaemia, interpret the iron studies, construct a prioritised problem list, and outline an integrated investigation and management plan with justification for each decision. [1]

Model Answer

Classification and interpretation of results (5 marks): [1]

1. Anaemia, microcytic (MCV 71 fL), hypochromic — the morphological bucket is microcytic, which immediately narrows the differential to iron deficiency, thalassaemia trait, anaemia of chronic disease, sideroblastic anaemia, or lead poisoning.
2. The iron studies confirm iron deficiency. Ferritin is 6 micrograms per litre (markedly low, well below the threshold of 30 for uncomplicated deficiency), transferrin is high at 4.1 g/L (the body upregulates transferrin in iron deficiency), and the transferrin saturation is 7 per cent (critically low). This is the classic iron deficiency pattern and the opposite of anaemia of chronic disease (which would have a normal or high ferritin and a low transferrin).
3. The reticulocyte count is low (1.0 per cent), confirming that the marrow is not responding — consistent with iron-deficient erythropoiesis, not haemolysis or recovery.
4. The CRP is normal (8 mg/L), so the ferritin of 6 is not falsely normalised by inflammation — this is uncomplicated iron deficiency.
5. The clinical context — dark stools positive for occult blood, weight loss, daily NSAID use — points to a gastrointestinal source of blood loss. The daily ibuprofen raises the possibility of an NSAID-induced gastroduodenal ulcer, but the weight loss mandates exclusion of colorectal or gastric malignancy. [1]

Problem list (3 marks): [1]

1. Severe iron deficiency anaemia (Hb 76 g/L) from chronic gastrointestinal blood loss — symptomatic, with exertional dyspnoea.
2. Likely gastrointestinal pathology — possible malignancy. Weight loss and occult blood in a 68-year-old man mandate urgent endoscopic investigation for gastric or colorectal cancer.
3. NSAID-related gastrointestinal bleeding — daily ibuprofen may be causing or contributing to a gastroduodenal erosion or ulcer.
4. Iatrogenic contribution — the ibuprofen should be ceased immediately. [1]

Investigation plan (5 marks): [1]

1. Urgent coeliac serology — anti-tissue transglutaminase IgA plus total IgA to exclude IgA deficiency. Coeliac disease is a common, treatable and easily missed cause of iron deficiency in adults [1].
2. Urgent oesophagogastroduodenoscopy (OGD) — to identify gastritis, peptic ulcer disease, gastric cancer, or the villous atrophy of coeliac disease (duodenal biopsies taken even if the mucosa appears normal).
3. Urgent colonoscopy — to identify colorectal cancer (the weight loss and occult blood make this the most dangerous possibility), polyps, or inflammatory bowel disease.
4. If both OGD and colonoscopy are negative, capsule endoscopy to examine the small bowel for angiodysplasia, Crohn's disease, or small bowel tumour.
5. Repeat FBC and iron studies after starting iron to confirm a reticulocyte response within 7 to 10 days and a haemoglobin rise of about 20 g/L over three weeks.

Management plan (5 marks): [1]

1. Stop the ibuprofen immediately and advise paracetamol-based analgesia. If an NSAID is essential, add a proton pump inhibitor or use a COX-2 selective agent.
2. Start oral iron replacement — ferrous sulfate 200 mg three times daily (or every other day to improve tolerance and absorption), for a minimum of three months to correct the haemoglobin and replete iron stores. Counsel on side effects (constipation, dark stools, nausea) and the expected timeline of response.
3. Urgent gastroenterology referral for OGD and colonoscopy — within two weeks given the suspicion of malignancy. The iron studies confirm the deficiency; the endoscopies find the cause [1].
4. Transfusion is not indicated at this time. The patient is chronically anaemic (not acute), is haemodynamically stable, and has no ischaemic features. The restrictive transfusion threshold of 70 g/L in a stable patient applies, and this patient's Hb of 76 g/L does not meet it — treating the iron deficiency is the correct approach. If he develops ischaemic chest pain or heart failure, transfuse a single unit at a time with diuretic cover [4].
5. Longitudinal follow-up: after GI management and iron repletion, recheck the FBC and ferritin at three months to confirm correction. If the iron deficiency recurs despite adequate iron and a negative initial workup, reassess for ongoing occult blood loss.

Communication and safety (2 marks): Explain to the patient that his anaemia is from iron loss in the bowel, that the ibuprofen is a likely contributor but the weight loss means a thorough search for a more serious cause is essential, and that the endoscopies will find and, if possible, treat the source. Document the discussion about stopping NSAIDs and the plan for urgent endoscopy. [1]

SAQ 2 — Interpreting a Macrocytic Anaemia and the B12/Folate Distinction (10 marks, 20 minutes)

Prompt: A 70-year-old woman presents with progressive fatigue, sore tongue, and numbness and tingling in her feet for four months. She is a strict vegan. FBC: Hb 72 g/L, MCV 118 fL, WCC 3.2 x 10^9/L (mildly low), platelets 110 x 10^9/L (mildly low). Blood film: oval macrocytes and hypersegmented neutrophils (six lobes). B12 85 pmol/L (low), folate 12 nmol/L (normal). Outline the diagnosis, the significance of the neurological symptoms, and the management, including the critical safety point regarding folate. [1]

Model Answer

Diagnosis (3 marks): This is megaloblastic anaemia from vitamin B12 deficiency. The triad is: a macrocytic anaemia (MCV 118 fL) with mild pancytopenia, a blood film showing the morphological hallmarks of megaloblastic haematopoiesis (oval macrocytes and hypersegmented neutrophils with six or more lobes), and a low serum B12 with a normal folate. The vegan diet is the likely cause (dietary B12 deficiency), though pernicious anaemia (autoimmune gastritis with anti-intrinsic factor antibodies) must also be considered in a woman of this age. The mild pancytopenia reflects ineffective haematopoiesis from impaired DNA synthesis affecting all three cell lines [2].

Significance of the neurological symptoms (3 marks): The numbness and tingling in her feet, in the context of B12 deficiency, is early peripheral neuropathy and potentially early subacute combined degeneration of the spinal cord. This is the critical distinction between B12 and folate deficiency: B12 deficiency damages the nervous system (the dorsal columns, causing loss of vibration and proprioception, and the lateral corticospinal tracts, causing weakness and extensor plantars), while folate deficiency produces the identical blood picture but no neurological features. The neurological deficit may not fully reverse if treatment is delayed, so the presence of neurological symptoms makes the treatment more urgent and more intensive. [1]

Management (4 marks): [1]

1. Intramuscular hydroxocobalamin is the treatment. Because there are neurological features, the intensive regimen is used: 1 mg IM on alternate days for up to two weeks (or until symptoms stop improving), then lifelong maintenance of 1 mg IM every two to three months [2].
2. The critical safety point: do not give folate alone. If folate is given to a B12-deficient patient without adequate B12 replacement, it can precipitate or accelerate subacute combined degeneration of the spinal cord — the folate corrects the blood picture (the megaloblastic anaemia improves) but does not address the neurological defect, while the B12 deficiency continues to damage the cord. Always check B12 before starting folate, or treat both together if there is combined deficiency.
3. Monitor potassium in the first week of treatment. As the megaloblastic marrow recovers and new cells are produced, they take up potassium from the blood, and hypokalaemia is a recognised early complication of B12 (or folate) replacement.
4. Investigate the cause. Check anti-intrinsic factor and anti-parietal cell antibodies to identify pernicious anaemia (which carries a risk of gastric carcinoma and requires lifelong maintenance B12 and consideration of endoscopic surveillance). If the cause is purely dietary, lifelong oral B12 between meals may be adequate after initial IM repletion, but IM maintenance is safer if compliance is uncertain.