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Classifying Anemia: A Systematic Clinical Approach

1Framing the Question: What 'Type of Anemia' Means and Why the Sequence Matters2History and Examination: Narrowing the Differential Before the Lab3The CBC and Red Cell Indices: Reading MCV, MCHC, and RDW4The Reticulocyte Count: The Central Branching Point5The Peripheral Smear: Confirming the Category and Finding the Specific Cause6Integrating the Findings: A Working Classification and Next Steps
The Peripheral Smear: Confirming the Category and Finding the Specific Cause

Shape and Chromia: What Each Finding Points To

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Each shape on this panel is a mechanism made visible. Target cells have extra membrane relative to their volume, which is why they appear in thalassemia and after splenectomy. Schistocytes are torn by mechanical shear, so they belong to microangiopathic haemolysis and mechanical valves. Spherocytes have lost membrane in pieces, which is the signature of hereditary spherocytosis and immune haemolysis. Bite cells have had a Heinz body plucked out by the spleen, pointing to oxidative haemolysis. Hypochromia is simply too little haemoglobin per cell, and it is the finding that, with the shape pattern, separates iron deficiency from thalassemia.
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Once size has been established, shape and chromia carry most of the diagnostic weight. Each named abnormality is produced by a specific mechanism, and the mechanism is what links the finding to a cause.

Target cells (codocytes) are red cells with a central haemoglobin dot surrounded by a pale ring and a second rim of haemoglobin. They form when the surface area of the membrane is increased relative to the cell volume, which happens in thalassemia, in liver disease, after splenectomy, and in haemoglobin C disease. In thalassemia trait the excess membrane is the direct result of unbalanced globin chain synthesis, so target cells appear alongside a normal or near-normal RDW.

Schistocytes are fragmented red cells — helmet shapes, triangles, and small irregular pieces. They are produced by mechanical shearing as cells pass through fibrin strands or damaged endothelium, so they point to microangiopathic haemolysis such as thrombotic thrombocytopenic purpura, haemolytic uraemic syndrome, or disseminated intravascular coagulation, and to mechanical valves. Spherocytes are round cells with no central pallor, produced when the membrane is lost in pieces; they are seen in hereditary spherocytosis and in immune haemolysis. Bite cells are red cells with a single semicircular defect, produced when the spleen removes a Heinz body from the membrane; they point to oxidative haemolysis from G6PD deficiency or oxidant drugs.

Hypochromia — central pallor wider than about one third of the cell diameter — reflects reduced haemoglobin content per cell. It is prominent in iron deficiency and in thalassemia, and it is the finding that, together with the shape pattern, separates the two.

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