When is a Peripheral Blood Smear Recommended?
A peripheral blood smear should be examined whenever there are abnormalities in the complete blood count beyond isolated findings, when specific hematologic disorders are suspected based on clinical presentation, or when certain infectious diseases require species identification or parasite quantification. 1
Primary Indications for Peripheral Smear Review
Hematologic Abnormalities
Evaluation of the peripheral blood smear by a qualified hematologist or pathologist is paramount when investigating suspected immune thrombocytopenia (ITP), as it can reveal abnormalities inconsistent with ITP such as schistocytes in thrombotic thrombocytopenic purpura-hemolytic uremic syndrome or leukocyte inclusion bodies in MYH9-related disease 1
The smear should be reviewed when there are abnormalities in the complete blood count and peripheral blood smear other than isolated thrombocytopenia (such as findings beyond microcytic anemia from chronic blood loss) 1
Excessive numbers of giant or small platelets on smear may indicate inherited thrombocytopenia and warrant further investigation 1
Pseudo-thrombocytopenia due to EDTA-dependent platelet agglutination must be excluded by peripheral smear examination 1
Suspected Primary Immunodeficiency Syndromes
Examination of a peripheral blood smear should be the first diagnostic test for suspected Chediak-Higashi syndrome (CHS), as patients have giant azurophilic lysosomal granules in all granulated cells that are pathognomonic for CHS 1
The smear is essential when CHS is suspected in patients with partial oculocutaneous albinism, bacterial infections, and progressive neurological symptoms 1
Peripheral smear examination helps identify Griscelli syndrome type 2 in patients with pigmentary dilution, neurological abnormalities, and pyogenic infections 1
Infectious Disease Diagnosis
Examining a peripheral blood smear for red blood cell fragmentation is necessary when hemolytic uremic syndrome (HUS) is suspected, particularly in patients with diagnosed E. coli O157 or STEC infection 1
Microscopy examination of thick and thin blood films (Giemsa stained) is the gold standard for malaria diagnosis, allowing detection of parasites, species identification, quantification of parasitemia, and differentiation between sexual and asexual forms 2, 3
Three thick and thin blood films performed over 72 hours are necessary to exclude malaria with confidence in febrile travelers returning from endemic areas, as a single blood film has insufficient sensitivity (only 74.1% when parasite densities are low) 3
Peripheral smear examination is critical when ehrlichiosis is suspected to identify intracytoplasmic inclusions (morulae) in monocytes, neutrophils, or bands 1
Myeloid/Lymphoid Neoplasms
Peripheral blood smear should be reviewed for evidence of other blood count abnormalities including eosinophilia, dysplasia, monocytosis, and circulating blasts when evaluating suspected myeloid/lymphoid neoplasms with eosinophilia 1
Laboratory testing should include peripheral blood smear review as part of the initial workup for hypereosinophilic syndromes 1
Drug-Associated Hemolysis
Peripheral smear examination is essential for early diagnosis and management of bite cell hemolytic anemia associated with oxidant drug injury, as bite cells are morphologically characteristic poikilocytes with semicircular portions removed from the cell margin 4
The usual biochemical markers of hemolysis are not consistently observed in bite cell hemolytic anemia, making peripheral smear examination particularly important 4
When Peripheral Smear is NOT Routinely Recommended
A peripheral white blood cell count and differential should not be performed to establish an etiology of diarrhea (though it may be useful clinically in specific contexts) 1
Fecal leukocyte examination should not be used to establish the cause of acute infectious diarrhea 1
Common Pitfalls to Avoid
Do not discharge a patient or delay malaria testing based on a single negative blood film, as parasitemia can be intermittent, particularly early in infection 3. The sensitivity of a single film drops significantly when parasite densities are low.
Do not overlook the peripheral smear when automated counts show isolated thrombocytopenia, as this may represent EDTA-dependent platelet agglutination (pseudo-thrombocytopenia) rather than true thrombocytopenia 1.
Do not rely solely on automated indices for anemia evaluation when there are atypical features, as the peripheral smear provides unique diagnostic information in approximately 6% of non-deficiency anemias and helpful information in another 25% of cases 5.