When is a peripheral smear (peripheral blood smear) recommended for a patient with a history of anemia or recent blood transfusion, presenting with symptoms suggestive of a hematological disorder?

Peripheral Smear Indications in Anemia and Hematological Disorders

A peripheral blood smear is mandatory for all patients with anemia or suspected hematological disorders, and must be reviewed before initiating any treatment to identify correctable causes and evaluate for dysplasia, blasts, or other morphologic abnormalities. 1

Mandatory Indications for Peripheral Smear Review

In Patients with Anemia

• Review the peripheral smear in every anemic patient to assess red blood cell morphology (size, shape, color, inclusions, arrangement) which provides critical diagnostic information that RBC indices alone cannot provide 1, 2, 3
• Examine for specific findings including anisocytosis, poikilocytosis, basophilic stippling, and Rouleaux formation to differentiate between iron deficiency, thalassemia, hemolysis, megaloblastic causes, and plasma cell disorders 1, 2, 3
• The smear must be reviewed before starting erythropoiesis-stimulating agents to exclude myelodysplastic syndromes, bone marrow failure, or other primary hematologic malignancies 1

In Patients with Recent Blood Transfusion History

• Perform peripheral smear review before transfusion when possible, as post-transfusion samples will contain donor red cells that obscure the patient's underlying RBC morphology 1
• If the patient has already been transfused, document this in the clinical history provided to the pathologist, as it may confound morphologic interpretation 1

When Hematological Disorder is Suspected

• Peripheral smear review is mandatory when the complete blood count shows any abnormality beyond isolated thrombocytopenia, including abnormal white blood cell count, presence of blasts, or multiple cytopenias 1, 2
• The pathologist must evaluate for blasts, immature cells, dysplastic features in any cell line, and abnormal cell populations that indicate acute leukemia, myelodysplastic syndromes, or other myeloid neoplasms 1, 2

Specific Clinical Scenarios Requiring Peripheral Smear

Myelodysplastic Syndrome Evaluation

• Peripheral smear is mandatory to evaluate dysplasia in erythroid, myeloid, and megakaryocytic lineages and to enumerate blasts 1, 2
• Look specifically for granulocyte nuclear hypolobation (pseudo Pelger-Huet), cytoplasmic hypogranulation, platelet anisocytosis, and giant platelets 1

Acute Leukemia Workup

• The pathologist must review the peripheral smear to enumerate blasts and assess for morphologic features that distinguish AML from ALL 1, 2
• Peripheral blood may be used for diagnosis and ancillary studies if bone marrow aspirate is inadequate and sufficient blasts are present 1

Immune Thrombocytopenia (ITP) Diagnosis

• Review the peripheral smear to confirm the presence of large platelets and exclude other abnormalities in white blood cells or red blood cells that would suggest an alternative diagnosis 1
• If abnormalities beyond thrombocytopenia are present (abnormal WBC count, morphology, or anemia not attributed to blood loss), bone marrow examination is required before diagnosing ITP 1

Systemic Mastocytosis Evaluation

• The peripheral smear must be reviewed for circulating mast cells (≥10% indicates mast cell leukemia vs <10% for aleukemic variant) and for evidence of associated hematologic neoplasms including dysplasia, monocytosis, or eosinophilia 1

Plasma Cell Disorders

• Examine for Rouleaux formation and circulating plasma cells; ≥20% plasma cells or absolute count >2×10⁹/L indicates plasma cell leukemia 2

Critical Pre-Analytical Considerations

• Blood smears must be properly prepared with adequate cell distribution for accurate morphological assessment 2
• Provide the pathologist with complete clinical history including age, prior malignancies, chemotherapy exposure, recent growth factor therapy, transfusions, or medications that may alter morphology 1, 2
• Recent confounding factors (growth factors within days, transfusions, G-CSF, steroids) must be documented as they can obscure dysplastic features or mimic abnormalities 1

Integration with Other Diagnostic Tests

The peripheral smear must be interpreted in conjunction with:

• Complete blood count with differential 1, 2
• Bone marrow examination (aspirate and biopsy) for definitive diagnosis of MDS, acute leukemia, or other marrow-based disorders 1
• Flow cytometry immunophenotyping to distinguish AML from ALL and identify abnormal populations 1, 2
• Cytogenetic analysis for prognostic assessment and diagnostic confirmation 1

Common Pitfalls to Avoid

• Never rely on automated counts alone when hematologic disorder is suspected; automated analyzers cannot detect blasts, dysplasia, or specific morphologic abnormalities 2, 4
• Do not diagnose ITP without peripheral smear review showing only thrombocytopenia with large platelets and no other abnormalities 1
• Failing to distinguish between relative and absolute cell counts (particularly in monocytosis) can lead to misdiagnosis 2
• Not performing peripheral smear when automated counts flag abnormalities delays diagnosis of serious conditions including acute leukemia 1, 2