What can a peripheral blood smear (PBS) tell me about my blood cells?

What a Peripheral Blood Smear Can Tell You

A peripheral blood smear provides critical diagnostic information about red blood cell morphology (size, shape, color, inclusions), white blood cell differential and morphology (nuclear and cytoplasmic abnormalities), platelet characteristics, and can identify circulating abnormal cells including blasts, dysplastic cells, and circulating plasma cells. 1

Red Blood Cell Assessment

The peripheral blood smear reveals essential RBC abnormalities that guide diagnosis:

• Size variations including microcytosis and macrocytosis help differentiate causes of anemia 1, 2
• Shape abnormalities (poikilocytosis) such as anisocytosis and basophilic stippling indicate specific disease processes 3, 2
• Color changes reflect hemoglobin content and can suggest iron deficiency or thalassemia 2
• RBC inclusions and arrangement patterns provide clues to hemolytic processes, metabolic disorders, and bone marrow dysfunction 2

In patients with pyruvate kinase deficiency, the smear typically shows unremarkable morphology with anisocytosis and poikilocytosis, and occasionally 3-30% echinocytes, particularly after splenectomy 3. Nucleated RBCs (erythroblasts) in peripheral blood indicate dysplastic erythropoiesis in myelodysplastic syndromes or severe ineffective erythropoiesis 3, 4.

White Blood Cell Evaluation

At least 200 circulating nucleated cells should be systematically analyzed, including a differential count of at least 100 WBCs 3, 1:

• Granulocyte abnormalities including nuclear hypolobation (pseudo Pelger-Huet), hypersegmentation, and cytoplasmic hypogranulation/degranulation suggest myelodysplastic syndromes 3
• Blast identification is critical—myeloblasts are defined by high nuclear/cytoplasmic ratio, visible nucleoli, fine nuclear chromatin, and variable cytoplasmic basophilia 3
• Monocyte count is essential for diagnosing chronic myelomonocytic leukemia, which requires persistent monocytosis >1×10⁹/L along with dysgranulopoiesis and presence of promonocytes or blasts 3

Circulating plasma cells warrant careful attention: ≥20% plasma cells and/or absolute count >2×10⁹/L establishes plasma cell leukemia, but lower thresholds (≥5% or ≥0.5×10⁹/L) should be documented as they may represent early aggressive disease 3, 1.

Platelet Assessment

The smear reveals platelet abnormalities including:

• Platelet anisocytosis and giant platelets suggest megakaryocytic dysplasia in myelodysplastic syndromes 3
• Platelet count estimation helps verify automated counts and identify severe thrombocytopenia 1

Critical Diagnostic Applications

For Myelodysplastic Syndromes

Peripheral blood smear examination is the mainstay for MDS diagnosis 3. The smear should be examined using May-Grünwald-Giemsa staining, counting at least 200 cells to assess dysplasia in erythroid, myeloid, and megakaryocytic lineages 3.

For Hematologic Malignancies

The smear identifies circulating blasts (peripheral blasts <5% in CMML, 5-19% in MDS) 3. Flow cytometry should complement morphology to confirm clonality and distinguish malignant from reactive processes 3, 1.

For Hemolytic Anemias

In hereditary hemolytic anemias like pyruvate kinase deficiency, the smear shows nonspecific findings, making it part of a broader diagnostic workup that excludes membrane disorders, unstable hemoglobins, and immune-mediated processes 3.

Integration with Additional Testing

Peripheral blood smear interpretation must be integrated with clinical history, complete blood count, and when indicated, flow cytometry, cytogenetic analysis, and bone marrow examination 1, 5. Flow cytometry is particularly valuable for detecting clonal populations, evaluating CD34+ cells, and distinguishing between reactive and neoplastic processes 3, 1.

Common Pitfalls

• Do not rely on flow cytometry blast percentages for prognosis—morphologic blast assessment by an experienced hematopathologist is required 3
• Recognize that circulating plasma cells are not always malignant—polyclonal plasma cells can appear transiently in sepsis, infectious mononucleosis, and serum sickness, requiring flow cytometry to demonstrate clonality 3
• Specimens should be processed within 24 hours of collection to ensure optimal morphologic assessment 1
• In pyruvate kinase deficiency, reticulocytosis may be disproportionately low relative to hemolysis severity due to splenic sequestration of younger cells 3