Peripheral Smear Findings
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Direct answer
A peripheral smear shows red cell morphology that points toward a specific cause, and the eight findings most examined are target cells, schistocytes, Howell-Jolly bodies, basophilic stippling, teardrop cells, spherocytes, Heinz bodies and rouleaux. Target cells suggest thalassaemia, haemoglobin C or liver disease; schistocytes point to microangiopathic haemolysis; Howell-Jolly bodies indicate absent splenic function. The smear must always be read alongside the indices, the reticulocyte count and the clinical context.
What you must remember
- Target cells: Thalassaemia, haemoglobin C and liver disease; excess membrane relative to haemoglobin content gives the bullseye appearance.
- Schistocytes: Helmet cells and fragments from mechanical shearing, seen in thrombotic thrombocytopenic purpura, haemolytic uraemic syndrome, disseminated intravascular coagulation and mechanical prosthetic valves.
- Howell-Jolly bodies: Nuclear DNA remnants normally removed by the spleen; present after splenectomy or functional asplenia, and in severe megaloblastic anaemia.
- Basophilic stippling: Aggregated ribosomal RNA; seen in lead poisoning, thalassaemia and sideroblastic anaemia, where Pappenheimer bodies may also appear.
- Teardrop cells (dacrocytes): Classically myelofibrosis and other marrow infiltration; also seen in thalassaemia.
- Spherocytes: Small dense cells without central pallor, seen in hereditary spherocytosis and autoimmune haemolytic anaemia; the osmotic fragility test supports the diagnosis.
- Heinz bodies: Denatured haemoglobin visible only on a supravital stain, typical of G6PD deficiency after an oxidant exposure.
- Rouleaux: Stacked red cells in multiple myeloma and in states of raised fibrinogen or immunoglobulin.
Worked scenario: a young woman with haemolysis
A 32-year-old woman presents with fatigue, jaundice and a haemoglobin of 8.1 g/dL, and the smear shows spherocytes with a raised reticulocyte count. The reasoning starts with whether the haemolysis is intrinsic to the red cell or driven by an immune process.
- Test for immune haemolysis: Spherocytes with a positive direct antiglobulin test point to autoimmune haemolysis.
- Test for hereditary spherocytosis: Spherocytes with a negative test and high osmotic fragility point to hereditary spherocytosis.
- Consider microangiopathy: If the film instead showed schistocytes with thrombocytopenia, the question would shift to microangiopathic haemolysis and the urgent search for thrombotic thrombocytopenic purpura.
- Name the measurements: A reticulocyte count, a direct antiglobulin test and an osmotic fragility test most often decide between these diagnoses.
The same red cell abnormality can thus lead to very different diagnoses, and the candidate must link the morphology to the test that separates them. Each test answers a different question.
Where the examiner misdirects you
Four morphology traps recur in examinations.
- Trap: Mistaking artefact for schistocytes. Correct: Burr cells, which are echinocytes with regular projections, appear in uraemia and on slow drying, so crenated cells in renal failure are not a microangiopathy.
- Trap: Reading a splenectomy patient with no Howell-Jolly bodies as normal. Correct: They are the expected finding after splenectomy, so their absence in a splenectomised patient suggests an accessory spleen.
- Trap: Diagnosing myelofibrosis from teardrop cells alone. Correct: Teardrop cells are often seen with myelofibrosis but are not specific to it, so they should be paired with leucoerythroblastic changes and a dry tap.
- Trap: Diagnosing G6PD deficiency from a routine smear. Correct: Heinz bodies are not visible on routine stains, so the question is testing the need for a supravital stain.
Frequently asked questions
Which peripheral smear finding indicates asplenia?
Howell-Jolly bodies are the peripheral smear finding that most reliably indicates asplenia, because the spleen normally removes nuclear remnants from red cells. They are seen after splenectomy and in functional asplenia, such as in coeliac disease or sickle cell disease. Their presence is a useful clue when the history of splenectomy is unclear.
What does a schistocyte on a peripheral smear suggest?
Schistocytes on a peripheral smear suggest microangiopathic haemolytic anaemia, in which red cells are mechanically fragmented in small vessels or on prosthetic valves. Thrombotic thrombocytopenic purpura, haemolytic uraemic syndrome and disseminated intravascular coagulation are the main causes to consider. Urgent evaluation is needed when schistocytes come with thrombocytopenia.
Why are teardrop cells associated with myelofibrosis?
Teardrop cells are associated with myelofibrosis because marrow fibrosis distorts red cells as they pass through the bone marrow and enter the circulation. Leucoerythroblastic changes on the same film support the diagnosis. Teardrop cells alone are not specific, so the marrow biopsy is needed for confirmation.
What peripheral smear finding is characteristic of lead poisoning?
Basophilic stippling is the characteristic smear finding of lead poisoning, reflecting inhibition of ribosomal RNA degradation within red cells. It is also seen in thalassaemia and sideroblastic anaemia, so it must be interpreted with the clinical picture. Blood lead level measurement is the confirmatory test.
How are Heinz bodies identified on a blood film?
Heinz bodies are identified by a supravital stain such as new methylene blue, because they are denatured haemoglobin inclusions that do not stain on a routine Leishman film. They are typical of G6PD deficiency after oxidant exposure, such as certain drugs or fava beans. Bite cells may be seen alongside them.