Anaemia — Systematic Workup Clinical Case

DCE Long Case

Patient brief (provided to trainee)

Patient: Mr Harjit Singh, 68 years old, retired taxi driver. [1]

Presenting complaint: Three months of progressive fatigue, exertional dyspnoea (now breathless walking up one flight of stairs), and a 6 kg unintentional weight loss. His wife has noticed he looks pale. He has noticed his stools are darker than usual but has not seen frank blood. [1]

Past history: Hypertension (10 years), osteoarthritis of both knees (15 years). No prior surgery. No family history of bowel cancer. [1]

Current medications: Amlodipine 10 mg daily, ibuprofen 400 mg three times daily for six months (self-medicated for knee pain, escalated from PRN). [1]

Social history: Never smoked, drinks 10 standard drinks per week. Migrated from India 40 years ago. Lives with his wife. Independent in activities of daily living. [1]

Examination findings (trainee elicits):

• Thin, pale-appearing man. Conjunctival pallor. No jaundice.
• Vital signs: BP 128/76, HR 92 regular, RR 18, SpO2 97 per cent room air, afebrile.
• Cardiovascular: no murmur, no signs of heart failure.
• Abdomen: soft, non-tender, no organomegaly, no masses.
• Digital rectal examination: dark brown stool, positive for occult blood.
• No lymphadenopathy. Neurological examination normal. [1]

Investigations:

• FBC: Hb 76 g/L, MCV 71 fL, MCH 22 pg, RBC 4.0 x 10^12/L, WCC 7.2 x 10^9/L, platelets 380 x 10^9/L.
• Reticulocyte count: 1.0 per cent (low).
• Ferritin 6 micrograms/L, transferrin 4.1 g/L (high), transferrin saturation 7 per cent.
• CRP 8 mg/L. U&E normal. LFTs normal. B12 180 pmol/L (low-normal), folate 15 nmol/L (normal).
• Coeliac serology: pending. [1]

Candidate's structured presentation (model)

Opening statement (SASPOP): [1]

"Mr Singh is a 68-year-old retired taxi driver who presents with three months of progressive fatigue, exertional dyspnoea, and six kilograms of unintentional weight loss, with darker-than-usual stools. He has hypertension and osteoarthritis, and he takes amlodipine and daily ibuprofen. On examination he is pale with no organomegaly, and his digital rectal examination is positive for occult blood." [1]

"His main problems are:

1. Severe iron deficiency anaemia — haemoglobin 76, microcytic, with iron studies confirming deficiency (ferritin 6, transferrin high, saturation 7 per cent) and a low reticulocyte count confirming underproduction
2. Possible gastrointestinal malignancy — the weight loss and occult blood in a 68-year-old man mandate urgent endoscopic investigation
3. NSAID-related gastrointestinal bleeding — daily ibuprofen for six months is a likely contributor to mucosal injury
4. Hypertension — relevant to transfusion decisions." [1]

"My immediate priorities are to stop the ibuprofen, start oral iron replacement, and arrange urgent coeliac serology, oesophagogastroduodenoscopy and colonoscopy to find and treat the source of bleeding." [1]

Classification and interpretation: [1]

"I classified this anaemia by the mean cell volume — it is microcytic at 71 femtolitres, which narrows the differential to iron deficiency, thalassaemia trait, anaemia of chronic disease, sideroblastic anaemia, or lead poisoning. The iron studies confirmed iron deficiency: the ferritin is 6 micrograms per litre (markedly low), the transferrin is high at 4.1 grams per litre, and the transferrin saturation is 7 per cent. The CRP is normal at 8, so the low ferritin is not falsely reassuring from inflammation — this is uncomplicated iron deficiency. The reticulocyte count is low at 1 per cent, confirming the marrow is not responding because it has no iron. The occult blood in the stool and the weight loss identify the gastrointestinal tract as the source of the iron loss [1]."

Management plan: [1]

1. Stop the ibuprofen immediately. NSAIDs inhibit cyclo-oxygenase, reducing protective gastric prostaglandins and causing mucosal erosion and ulceration. Switch to paracetamol 1 g QID for the knee pain; if an anti-inflammatory is essential, add a proton pump inhibitor or use a COX-2 selective agent.
2. Start oral ferrous sulfate 200 mg three times daily for a minimum of three months — to correct the haemoglobin and replete iron stores. Counsel that dark stools are expected, that constipation is common, and that a reticulocyte response within 7 to 10 days confirms absorption. Alternative oral salts (ferrous fumarate, ferrous gluconate) if not tolerated.
3. Urgent gastroenterology referral for OGD and colonoscopy within two weeks. The weight loss and occult blood make malignancy the most dangerous possibility. Coeliac serology is pending; the OGD should include duodenal biopsies even if the mucosa appears normal.
4. Do not transfuse at this time. He is chronically anaemic, haemodynamically stable (BP 128/76, HR 92), and has no ischaemic features. The restrictive threshold of 70 grams per litre in a stable patient is not met at 76, and the TRICC trial and AABB guideline support withholding transfusion [3] [4]. If he develops ischaemia or heart failure, the threshold rises to 80 and I would transfuse a single unit at a time.
5. Follow-up: recheck the FBC and iron studies at four weeks to confirm a response, and at three months to confirm repletion. If the iron deficiency recurs despite adequate management, reassess for ongoing occult blood loss.

Examiner discussion questions

Q: "His B12 is 180 pmol per litre — is that a problem?" [1]

"It is low-normal, not frankly deficient. In the context of iron deficiency, a borderline B12 does not change the immediate management — I would correct the iron deficiency first and recheck the B12. If the MCV rises above 100 after iron repletion, or if the haemoglobin does not recover as expected, I would investigate B12 deficiency further with methylmalonic acid and homocysteine levels, which are more sensitive than the serum B12 alone. The point is that iron deficiency can mask a coexisting B12 deficiency, because the two size effects cancel out — if his MCV normalises after iron alone, that suggests a macrocytic process was hidden [2]."

Q: "What would the colonoscopy show, and how would it change your management?" [1]

"If it shows a colorectal cancer, he would be referred to a colorectal surgeon and a multidisciplinary team for staging CT and surgical resection — and the iron deficiency would be managed as part of his perioperative and oncological care, with intravenous iron to optimise his haemoglobin before surgery under a patient blood management protocol. If it shows a large adenomatous polyp, it would be removed endoscopically and he would enter a surveillance programme. If it shows inflammatory bowel disease, that would explain the iron loss and he would be treated with specific therapy plus iron repletion. If both the OGD and colonoscopy are negative, I would arrange capsule endoscopy to examine the small bowel for angiodysplasia, Crohn's disease, or a small bowel tumour." [1]

Q: "Why not give intravenous iron rather than oral iron?" [1]

"Oral iron is first-line because it is effective, cheap, and safe. Intravenous iron is reserved for specific indications: intolerance to oral iron, non-absorption (such as in active inflammatory bowel disease, coeliac disease, or post-bariatric surgery), ongoing blood loss that outpaces oral absorption, or perioperative optimisation where there is not enough time for oral iron to work. This patient has none of those indications at present — he is an outpatient, his gut is absorbing (the reticulocyte count will confirm this), and he has time for oral iron to work. If the OGD shows active inflammatory bowel disease or severe gastritis, or if his haemoglobin does not rise as expected, I would switch to intravenous ferric carboxymaltose." [1]

Q: "What is the most dangerous error a candidate can make in this case?" [1]

"Closing the workup at the iron study. The iron study confirms the deficiency; it does not find the cause. A candidate who prescribes iron and rechecks the haemoglobin in three months has improved the blood count — but if this man has a right-sided colon cancer, three months of delay could be the difference between a curative resection and palliative care. The discipline is: confirm the deficiency, then find and treat the source. The British Society of Gastroenterology guideline is explicit that every man and every postmenopausal woman with iron deficiency anaemia is investigated for a GI source [1]."

DCE Short Case — Blood Film and FBC Interpretation

Instruction

"Interpret this full blood count and blood film and discuss your approach. You have 4 minutes to interpret and 6 minutes for discussion." [1]

Provided data: A 50-year-old man with fatigue and jaundice. Hb 65 g/L, MCV 96 fL, reticulocyte count 9 per cent. LDH 1100 U/L (raised), haptoglobin less than 0.1 g/L (undetectable), unconjugated bilirubin 72 micromol/L. Blood film: spherocytes, polychromasia. DAT positive for IgG, negative for C3d. [1]

Presentation template

"I classify this anaemia as normocytic — the MCV is 96 femtolitres. The reticulocyte count is high at 9 per cent, which is the kinetic discriminator: it tells me the marrow is responding vigorously, so the problem is loss or destruction of red cells, not underproduction. The haemolysis screen confirms haemolysis — the LDH is raised at 1100, the haptoglobin is undetectable at less than 0.1, and there is unconjugated hyperbilirubinaemia at 72. The blood film shows spherocytes (small, dense cells with no central pallor) and polychromasia (large blue cells, which are the reticulocytes seen on the film). The direct antiglobulin test is positive for IgG and negative for C3d." [1]

"This is warm autoimmune haemolytic anaemia. The IgG positivity on the DAT defines it as warm — the antibodies bind at body temperature and the coated cells are removed by splenic macrophages, producing spherocytes as the membrane is nibbled away. The first-line treatment is prednisolone 1 to 1.5 milligrams per kilogram per day. I would also look for an underlying cause — lymphoproliferative disease, a connective tissue disease, or a drug trigger — because warm AIHA is often secondary." [1]

Discussion

Examiner: "Would you transfuse this patient?" [1]

"Only if he is symptomatic or haemodynamically unstable. Transfusion in autoimmune haemolysis is difficult because the autoantibody cross-reacts with donor cells — the crossmatch may be unreliable, and the transfused cells may be destroyed as fast as the patient's own. If his haemoglobin is falling rapidly, if he has chest pain or ischaemia, or if he is haemodynamically unstable, I would transfuse using the least incompatible unit, accepting that the transfusion is a bridge to definitive treatment with steroids, not a cure. If he is stable at 65 with a high reticulocyte count, the marrow is working — I would start steroids immediately and transfuse only if he deteriorates." [1]

Examiner: "Name three non-immune causes of a haemolytic anaemia with a negative DAT." [1]

"First, hereditary spherocytosis — a membrane protein defect (ankyrin, spectrin, band 3) producing spherocytes and extravascular haemolysis; confirmed by the EMA binding test or osmotic fragility. Second, G6PD deficiency — an X-linked enzyme deficiency producing episodic oxidative haemolysis after fava beans, infections, or oxidant drugs, with bite cells and Heinz bodies on the film. Third, microangiopathic haemolytic anaemia — from DIC, TTP, HUS, HELLP, or a mechanical heart valve — producing schistocytes (fragmented cells) on the film. A fourth would be paroxysmal nocturnal haemoglobinuria, a complement-mediated intravascular haemolysis with a negative or C3-only DAT, classically presenting with morning haemoglobinuria and venous thrombosis." [1]

Examiner: "What is the role of the reticulocyte count in classifying anaemia?" [1]

"It is the kinetic discriminator. A high reticulocyte count — above 2 per cent, or an absolute count above 100 times 10 to the 9 per litre — means the marrow is responding to the anaemia by pushing out young cells, so the problem is loss or destruction (haemolysis, acute bleeding, or recovery after treatment). A low reticulocyte count means the marrow is the bottleneck — underproduction from iron, B12, or folate deficiency, anaemia of chronic disease, chronic kidney disease, or marrow failure. The reticulocyte count is the first test after the FBC and film because it divides the entire differential of anaemia into two mechanistic groups with completely different workups." [1]