What information will a Complete Blood Count (CBC) with peripheral smear provide about a patient's blood cell count and morphology?

What a CBC with Peripheral Smear Tells You

A CBC with peripheral smear provides comprehensive information about blood cell counts, morphology, and distribution patterns that can diagnose or exclude hematologic malignancies, hemolytic processes, infections, and dysplastic disorders—information that automated counts alone cannot provide. 1

Red Blood Cell Information

The peripheral smear reveals critical RBC morphology and distribution patterns:

• Size variations including microcytosis and macrocytosis that indicate specific types of anemia 2
• Rouleaux formation suggesting plasma cell disorders like multiple myeloma 1
• Red blood cell fragments (schistocytes) indicating hemolytic uremic syndrome or other microangiopathic hemolytic anemias 1
• Shape abnormalities that automated analyzers may miss or misinterpret 3

White Blood Cell Information

The smear provides detailed WBC assessment beyond automated differentials:

• Differential count of neutrophils, lymphocytes, monocytes, eosinophils, and basophils with morphologic correlation 1
• Blast cells or immature cells crucial for detecting acute leukemia or myeloid neoplasms 1
• Dysplastic features in neutrophils (hypersegmentation, hyposegmentation) and cytoplasmic changes (toxic granulation, vacuolization) suggesting myelodysplastic syndromes 4, 2
• Monocyte morphology including assessment for dysgranulopoiesis, promonocytes, and neutrophil precursors in cases of persistent monocytosis 1, 5
• Large granular lymphocytes when flow cytometry suggests this diagnosis 4, 1
• Infectious organisms such as morulae in monocytes indicating ehrlichiosis 1, 5

Platelet Information

The smear evaluates platelet parameters that automated counts may misrepresent:

• Platelet count estimation to verify automated counts, especially in thrombocytopenia 1
• Platelet size and morphology including presence of large platelets 4
• Platelet clumping that can cause falsely low automated platelet counts 6

Plasma Cell Detection

The smear is essential for identifying circulating plasma cells:

• Circulating plasma cells ≥20% or absolute count >2×10⁹/L establishes plasma cell leukemia diagnosis 4, 1
• Lower thresholds (≥5% or ≥0.5×10⁹/L) should be documented as they may represent early plasma cell leukemia 4, 1
• Transient polyclonal plasma cells in non-malignant conditions must be distinguished from malignant processes 1

Clinical Contexts Requiring Peripheral Smear

Specific clinical scenarios where the smear provides critical diagnostic information:

• Suspected hematologic malignancies including leukemia, lymphoma, and myelodysplastic syndromes 4, 1
• Unexplained cytopenias to assess for dysplasia and exclude bone marrow failure syndromes 4
• Persistent monocytosis to evaluate for chronic myelomonocytic leukemia 1, 5
• Suspected hemolytic processes to identify schistocytes or other RBC abnormalities 1
• Infectious disease evaluation particularly for tick-borne illnesses like ehrlichiosis 1, 5
• Verification of automated analyzer flags that suggest abnormal cells or morphology 6

Integration with Other Tests

The peripheral smear must be interpreted alongside:

• Complete blood count parameters including hemoglobin, white blood cell count, and platelet count 4, 1
• Clinical history including age, sex, ethnicity, prior malignancies, cytotoxic therapy exposure, and family history 1, 2
• Recent confounding factors such as growth factor therapy, transfusions, or medications 1
• Flow cytometry to confirm clonality and evaluate specific cell markers when malignancy is suspected 4, 1, 2
• Bone marrow examination when peripheral findings suggest marrow pathology 4, 5

Critical Pitfalls to Avoid

• Relying solely on automated counts without smear review when abnormalities are flagged can delay diagnosis of serious conditions 1, 6
• Failing to distinguish relative from absolute cell counts particularly in monocytosis evaluation 1, 5
• Missing low-level circulating plasma cells that may represent early aggressive disease 4, 1
• Not performing smear review in suspected STEC infection where early HUS detection is critical 1
• Overlooking infectious organisms like ehrlichia morulae in appropriate clinical contexts 1, 5