When is a Peripheral Blood Smear Recommended?
A peripheral blood smear should be performed when there are abnormalities in the complete blood count beyond isolated thrombocytopenia or findings consistent with iron deficiency anemia, when hemolytic anemia is suspected, when evaluating suspected hematologic malignancies, as the first-line diagnostic test for Chediak-Higashi syndrome, and when hemolytic uremic syndrome (HUS) is suspected. 1
Hematologic Malignancies and Primary Immunodeficiencies
Examination of a peripheral blood smear should be the first diagnostic test for suspected Chediak-Higashi syndrome, as giant azurophilic lysosomal granules in all granulated cells are pathognomonic for this condition. 1
Review the peripheral blood smear for evidence of other blood count abnormalities including eosinophilia, dysplasia, monocytosis, and circulating blasts when evaluating myeloid/lymphoid neoplasms with eosinophilia. 1
Peripheral blood smear review is essential for identifying specimens that may require flow cytometric immunophenotyping when hematolymphoid neoplasms are suspected, and can sometimes establish a definitive diagnosis (such as chronic lymphocytic leukemia) without bone marrow evaluation. 2
Immune Thrombocytopenia (ITP)
In patients presenting with suspected ITP, abnormalities in the complete blood count and peripheral blood smear other than thrombocytopenia (and perhaps microcytic anemia attributed to chronic blood loss) should be further investigated before confirming the diagnosis of ITP. 1
A bone marrow examination is not necessary in patients presenting with typical ITP findings on peripheral smear. 1
Hemolytic Uremic Syndrome (HUS)
Examining a peripheral blood smear for the presence of red blood cell fragmentation is necessary when HUS is suspected (strong recommendation, high-quality evidence). 1
This should be performed alongside frequent monitoring of hemoglobin, platelet counts, electrolytes, and renal function in patients with diagnosed E. coli O157 or STEC infection, especially those producing Shiga toxin 2 or with bloody diarrhea. 1
Hemolytic Anemia
A peripheral blood smear should be performed when hemolysis is present to identify abnormal red blood cell morphologies that help differentiate between hemoglobinopathies, membranopathies, enzymopathies, immune-mediated anemias, and extrinsic causes. 3
Laboratory findings confirming hemolysis (reticulocytosis, increased lactate dehydrogenase, increased unconjugated bilirubin, decreased haptoglobin) should prompt peripheral smear examination. 3
Malaria Diagnosis
Microscopy examination of thick and thin blood films (peripheral blood smears) remains the gold standard for malaria diagnosis because it allows detection of parasites, species identification, quantification of parasitemia, and differentiation between sexual and asexual forms. 1, 4
Three thick and thin blood films performed over 72 hours are necessary to exclude malaria with confidence, as a single blood film has insufficient sensitivity (only 74.1% when parasite densities are low). 4
Any febrile traveler returning from a malaria-endemic area must undergo immediate peripheral blood smear examination for malaria. 5, 4
Common Pitfalls to Avoid
Do not order a peripheral blood smear routinely for all anemic patients, as RBC indices perform equally well for detecting iron deficiency or vitamin B12/folate deficiency, and the incremental value of physician review beyond laboratory reading is limited (only 4% of cases). 6
Do not rely on a single negative blood smear to rule out malaria—three negative smears at 12-hour intervals are necessary to exclude the diagnosis, as parasitemia can be intermittent. 5, 4
Do not discharge patients with suspected HUS without examining the peripheral blood smear for red blood cell fragments, as this is a critical diagnostic finding that precedes renal injury. 1
When peripheral blood smear and flow cytometry results do not explain clinical findings, recognize that additional evaluation may be needed, particularly in older patients who may have monoclonal B lymphocytosis or T-cell clonopathy of uncertain significance. 2