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PA14.1-2 | Microcytic Anemias — PBL Case

CLINICAL SETTING

Vikram, a 40-year-old man, is referred to the internal medicine outpatient department of a tertiary care hospital in Kolkata by a factory doctor. For the past eight months he has had fatigue, mild abdominal discomfort, and intermittent nausea. He has worked for 14 years at a battery recycling plant — smelting, plate cutting, and acid handling. He denies alcohol use and has no significant medical history. On examination: pallor +, faint scleral icterus, and a bluish line along the gingival margin. His spleen is just palpable. CBC ordered: Hb 10.2 g/dL, MCV 71 fL, RDW 22% (markedly elevated), WBC 8,600/µL with normal differential, platelets 195,000/µL. The treating consultant orders iron studies and a peripheral blood smear, and asks the junior residents to present a differential diagnosis for microcytic anaemia before the results return.

Trigger 1: Vikram's Story: A Clue in the Gums

The resident notes a bluish-black discolouration along the gingival margin ('Burton's line') and asks the consultant whether this is clinically relevant. The consultant nods and asks the group to reason from first principles: 'If you see microcytic anaemia with a dramatically elevated RDW in a man with 14 years of occupational metal exposure, what is on your differential — and what is the mechanism that links his job to his blood count?'

DISCUSSION POINTS

  • List the TAILS differential diagnoses for microcytic anaemia (MCV < 80 fL). For each, state whether you would expect a HIGH or LOW RDW, and explain why.
  • Iron is required at the final step of haem synthesis — the insertion of Fe²⁺ into protoporphyrin IX by ferrochelatase. Which enzyme earlier in the same pathway does heavy metal exposure inhibit, and how does that produce a microcytic anaemia?
  • Vikram's RDW is 22%. What does a markedly elevated RDW signify on a peripheral smear, and how does this help you prioritise between IDA and thalassaemia trait as a differential?
  • What is the significance of the gingival line, and what does it tell you about the duration and severity of Vikram's occupational exposure?
Click to reveal Trigger 2: The Blood Smear and the Iron Studies (discuss previous trigger first!)

Trigger 2: The Blood Smear and the Iron Studies

The peripheral blood smear report: Two distinct red cell populations visible — one normochromic normocytic, the other hypochromic microcytic. Coarse basophilic stippling present in approximately 15% of red cells. No spherocytes. No target cells. No nucleated RBCs. Iron studies: serum iron 68 µg/dL (mildly low), TIBC 195 µg/dL (low; normal 250–370), transferrin saturation 35% (normal to mildly elevated), serum ferritin 420 ng/mL (markedly elevated). Blood lead level: 72 µg/dL (severely elevated; normal < 10 µg/dL).

DISCUSSION POINTS

  • The peripheral smear shows a DIMORPHIC red cell population. What does this mean, and why does sideroblastic anaemia produce two morphologically distinct populations of red cells rather than a single uniformly microcytic picture?
  • Coarse basophilic stippling is visible in 15% of red cells. What are basophilic stipples made of, why do they appear in lead poisoning specifically, and how does this differ from the fine stippling seen in other conditions?
  • Vikram's ferritin is 420 ng/mL despite a low serum iron. Is this contradictory? Explain the iron-study pattern in sideroblastic anaemia — specifically, why transferrin saturation is elevated rather than low as in IDA.
  • Compare Vikram's peripheral smear findings with what you would expect to see in IDA, thalassaemia trait, and anaemia of chronic disease. Identify ONE smear feature that is unique to sideroblastic/lead anaemia and not found in the other three.
Click to reveal Trigger 3: Integrating the Differential: From Smear to Management (discuss previous trigger first!)

Trigger 3: Integrating the Differential: From Smear to Management

The diagnosis of lead-induced sideroblastic anaemia is confirmed. The occupational health team is notified. The consultant explains that a bone marrow aspirate with Prussian blue staining would show ring sideroblasts. Vikram is started on chelation therapy (DMSA — dimercaptosuccinic acid). The team uses this case to review the complete diagnostic algorithm for microcytic anaemia: from MCV to ferritin to smear to HPLC — and to discuss when a bone marrow is and is not needed.

DISCUSSION POINTS

  • Outline the step-by-step diagnostic algorithm for a patient presenting with MCV < 80 fL. At which step does ferritin measurement occur, what result would direct you toward IDA vs ACD vs sideroblastic anaemia, and when would you proceed to HPLC?
  • The bone marrow Prussian blue stain shows ring sideroblasts. Define a ring sideroblast precisely: what staining pattern is required, what percentage of erythroblasts must be involved for the diagnosis, and what do the iron granules in the ring represent biologically?
  • In anaemia of chronic disease (ACD), hepcidin is elevated. Explain the hepcidin mechanism step-by-step — from the inflammatory trigger through IL-6 to ferroportin degradation — and describe how this produces a pattern of 'iron-restricted erythropoiesis' that mimics early IDA on the smear.
  • If Vikram also had a concurrent iron deficiency (from dietary lack), how would the smear appearance change? What additional laboratory parameter would you use to differentiate concurrent IDA from pure sideroblastic anaemia in this setting?

Group Task Assignments

Group 1: Iron metabolism — absorption, transport, storage, regulation

  • Draw the complete iron absorption pathway from the duodenal lumen to plasma: DMT1, ferroportin, hephaestin, transferrin, transferrin receptor. Label where hepcidin acts and what happens to ferroportin when hepcidin levels are high.
  • Explain the 'ferritin paradox': why is serum ferritin a reliable marker of iron stores in a healthy person but unreliable in the setting of inflammation, chronic disease, or liver injury? Which test should replace ferritin in these settings, and why?

Competencies: PA14.1

Group 2: Stages of iron depletion and the RDW early-warning sign

  • Describe the three stages of iron depletion (storage depletion → transport iron depletion → iron deficiency anaemia) and list the single laboratory parameter that changes at each stage, in the order it changes.
  • Explain why the RDW rises BEFORE the MCV falls in early IDA. Draw a simple graph showing the sequence: ferritin, RDW, MCV, and Hb plotted against months of progressive iron depletion.

Competencies: PA14.1

Group 3: Peripheral smear interpretation in microcytic anaemias

  • Describe the peripheral smear findings for each of the four TAILS differentials (IDA, beta-thalassaemia trait, ACD, sideroblastic anaemia) using the four-parameter RBC framework: size, colour, shape, and content/inclusions.
  • Identify the single most diagnostically valuable smear finding for EACH differential: pencil cell (IDA), disproportionate microcytosis with target cells (thal trait), mild hypochromia with few poikilocytes (ACD), dimorphic population with coarse basophilic stippling (sideroblastic). Explain the mechanism behind each.

Competencies: PA14.2

Group 4: Hepcidin axis and ACD pathogenesis

  • Trace the ACD pathway from chronic inflammation → IL-6 → liver hepcidin → ferroportin degradation → trapped iron in macrophages → iron-restricted erythropoiesis → microcytic/normocytic hypochromic anaemia.
  • Compare the iron study panel results in IDA versus ACD: fill a table with serum iron, TIBC, transferrin saturation, ferritin, and soluble transferrin receptor (sTfR) for each condition and explain the mechanism behind each difference.

Competencies: PA14.1

Group 5: Diagnostic algorithm and bone marrow interpretation

  • Construct a decision tree for microcytic anaemia starting from MCV < 80 fL, branching through ferritin, transferrin saturation, TIBC, and HPLC to arrive at each of the four TAILS diagnoses.
  • Define ring sideroblasts precisely and explain the Prussian blue staining principle. Under what two clinical scenarios (one acquired, one congenital) would you expect ring sideroblasts, and what metabolic step is blocked in each?

Competencies: PA14.1, PA14.2

Learning Issues

Research these questions and bring your findings to the discussion.

  1. [PA14.1] What is the complete iron absorption, transport, storage, and regulatory pathway (including hepcidin), what are the three stages of iron depletion and their sequential laboratory markers, and how do the iron study patterns differ across IDA, ACD, and sideroblastic anaemia?
  2. [PA14.2] What are the characteristic peripheral smear findings in each microcytic anaemia differential (IDA, thalassaemia trait, ACD, sideroblastic/lead anaemia), how is smear morphology interpreted using the size-colour-shape-content framework, and when does the smear alone direct the diagnosis?