A peripheral blood smear is a laboratory test where a drop of blood is spread thinly on a glass slide, usually with Wright-Giemsa stain, and examined under a microscope.
The examination should follow a structured approach.
Key indications include unexplained cytopenias, leukocytosis, lymphocytosis, suspected leukemia or lymphoma, unexplained jaundice, and when automated analyzers detect blast cells or atypical lymphocytes.
The examination begins with low-power screening (10× objective) to identify microfilariae or other large abnormalities, followed by detailed oil immersion examination (100× objective).
A minimum of 100 microscopic fields should be examined.
The blood smear provides valuable information about blood cells that automated counters may miss.
A blood smear review involves systematic microscopic examination of peripheral blood to assess the size, shape, and number of red blood cells, white blood cells, and platelets, providing critical diagnostic information that automated analyzers cannot detect.
The peripheral blood smear provides diagnostic clues that guide further testing and treatment.
Blood smears are used to evaluate abnormal complete blood count (CBC) results, diagnose blood disorders, assess response to treatment, and identify infections or parasites.
They’re particularly useful when automated analyzers flag abnormalities or when clinical suspicion exists for conditions like anemia, leukemia, or thrombocytopenia.
Normal Findings Normal RBCs are round, biconcave discs with central pallor, occupying about one-third of the cell diameter.
They measure approximately 7-8 micrometers and show uniform size (normocytic) and color (normochromic).
White Blood Cells (WBCs): Normal differential includes neutrophils (50-70%), lymphocytes (20-40%), monocytes (2-10%), eosinophils (1-4%), and basophils (<1%).
Cells should appear mature with normal nuclear and cytoplasmic features.
Platelets: Should appear as small purple fragments, scattered individually or in small clumps, numbering 150,000-400,000/µL.
Pathological RBC Findings
Size Abnormalities: Microcytosis (small cells): iron deficiency anemia, thalassemia, chronic disease
Macrocytosis (large cells): vitamin B12/folate deficiency, liver disease, alcoholism, hypothyroidism
Anisocytosis (variation in size): various anemias
Shape Abnormalities (Poikilocytosis):
Spherocytes (round, no central pallor): hereditary spherocytosis, autoimmune hemolytic anemia or alloimmune hemolytic anemia, with direct antiglobulin testing distinguishing between these etiologies.
Sickle cells: sickle cells confirm sickle cell disease particularly important when evaluating acute chest syndrome.
Target cells: liver disease, thalassemia, hemoglobin C disease, hemoglobin E disease rather than iron deficiency anemia, prompting hemoglobin electrophoresis showing elevated hemoglobin A2 (>3.5%) in β-thalassemia minor.
Schistocytes (fragmented red cells): microangiopathic hemolytic anemia, DIC, mechanical heart valves, which may indicate thrombotic thrombocytopenic purpura, hemolytic-uremic syndrome, disseminated intravascular coagulation, or pregnancy-associated hypertension—all requiring urgent evaluation.
Elliptocytes/ovalocytes: hereditary elliptocytosis, iron deficiency
Acanthocytes (spur cells): liver disease, abetalipoproteinemia
Echinocytes (burr cells): uremia, artifact from specimen handling
Teardrop cells: myelofibrosis, severe anemia, thalassemia
Color Abnormalities:
Hypochromia (pale cells): iron deficiency, thalassemia Polychromasia (bluish-gray cells): reticulocytosis, indicating active RBC production
Inclusions:
Howell-Jolly bodies (nuclear remnants): asplenia, severe hemolytic anemia
Basophilic stippling: lead poisoning, thalassemia
Parasites: malaria (Plasmodium species), babesiosis
Both thick and thin blood films should be prepared for optimal parasite detection, with thick films offering superior sensitivity for low-level parasitemia and thin films providing ideal morphology for species identification.
Heinz bodies: G6PD deficiency, oxidative damage
Rouleaux formation: RBCs stacked like coins, seen in multiple myeloma, chronic inflammation
WBC Abnormalities
Quantitative: Leukocytosis (elevated), leukopenia (decreased), or specific increases/decreases in particular cell types
Qualitative: Left shift: immature neutrophils (bands, metamyelocytes), seen in bacterial infection
Blast cells: immature cells suggesting acute leukemia
Atypical lymphocytes: viral infections (especially Epstein-Barr virus)
Toxic granulation: severe infection, inflammation
Döhle bodies: infection, pregnancy
Hypersegmented neutrophils: vitamin B12/folate deficiency
Platelet Abnormalities Giant platelets: immune thrombocytopenia, myeloproliferative disorders
Platelet clumping: may cause falsely low automated counts
Decreased number: thrombocytopenia from various causes
The smear also monitors disease progression and treatment response.
White Blood Cell Morphology
Auer rods, which are a pink-red needle-like cytoplasmic inclusions, which are pathognomonic for acute myelogenous leukemia.
Smudge cells/ruptured lymphocytes strongly suggest chronic lymphocytic leukemia, requiring flow cytometry for confirmation.
Hypogranular, hypolobulated neutrophils are characteristic of myelodysplastic syndromes, particularly when accompanied by macrocytic red cells.
Conversely, hypolobulated neutrophils with large red cells specifically suggest SF3B1-mutant MDS.
Circulating blasts (up to 20%) indicate advanced MDS or acute leukemia, necessitating bone marrow examination.
Dysplastic features in multiple cell lines (dyserythropoiesis, dysgranulopoiesis, dysmegakaryopoiesis) mandates bone marrow aspirate and biopsy with cytogenetic analysis for definitive MDS diagnosis.
Microangiopathic changes require immediate ADAMTS-13 testing, coagulation studies, and renal function assessment to evaluate for thrombotic thrombocytopenic purpura or disseminated intravascular coagulation.
Blast cells or Auer rods require urgent bone marrow examination, flow cytometry, and cytogenetic testing including Philadelphia chromosome analysis.
The morphologic pattern guides molecular testing—for example, ringed sideroblasts prompt SF3B1 mutation analysis in MDS.
A peripheral blood smear is a laboratory test where a drop of blood is spread thinly on a glass slide, usually with Wright-Giemsa stain, and examined under a microscope.
The examination should follow a structured approach.
Key indications include unexplained cytopenias, leukocytosis, lymphocytosis, suspected leukemia or lymphoma, unexplained jaundice, and when automated analyzers detect blast cells or atypical lymphocytes.
The examination begins with low-power screening (10× objective) to identify microfilariae or other large abnormalities, followed by detailed oil immersion examination (100× objective).
A minimum of 100 microscopic fields should be examined.
The blood smear provides valuable information about blood cells that automated counters may miss.
A blood smear review involves systematic microscopic examination of peripheral blood to assess the size, shape, and number of red blood cells, white blood cells, and platelets, providing critical diagnostic information that automated analyzers cannot detect.
The peripheral blood smear provides diagnostic clues that guide further testing and treatment.
Blood smears are used to evaluate abnormal complete blood count (CBC) results, diagnose blood disorders, assess response to treatment, and identify infections or parasites.
They’re particularly useful when automated analyzers flag abnormalities or when clinical suspicion exists for conditions like anemia, leukemia, or thrombocytopenia.
Normal Findings Normal RBCs are round, biconcave discs with central pallor, occupying about one-third of the cell diameter.
They measure approximately 7-8 micrometers and show uniform size (normocytic) and color (normochromic).
White Blood Cells (WBCs): Normal differential includes neutrophils (50-70%), lymphocytes (20-40%), monocytes (2-10%), eosinophils (1-4%), and basophils (<1%).
Cells should appear mature with normal nuclear and cytoplasmic features.
Platelets: Should appear as small purple fragments, scattered individually or in small clumps, numbering 150,000-400,000/µL.
Pathological RBC Findings
Size Abnormalities: Microcytosis (small cells): iron deficiency anemia, thalassemia, chronic disease
Macrocytosis (large cells): vitamin B12/folate deficiency, liver disease, alcoholism, hypothyroidism
Anisocytosis (variation in size): various anemias
Shape Abnormalities (Poikilocytosis):
Spherocytes (round, no central pallor): hereditary spherocytosis, autoimmune hemolytic anemia or alloimmune hemolytic anemia, with direct antiglobulin testing distinguishing between these etiologies.
Sickle cells: sickle cells confirm sickle cell disease particularly important when evaluating acute chest syndrome.
Target cells: liver disease, thalassemia, hemoglobin C disease, hemoglobin E disease rather than iron deficiency anemia, prompting hemoglobin electrophoresis showing elevated hemoglobin A2 (>3.5%) in β-thalassemia minor.
Schistocytes (fragmented red cells): microangiopathic hemolytic anemia, DIC, mechanical heart valves, which may indicate thrombotic thrombocytopenic purpura, hemolytic-uremic syndrome, disseminated intravascular coagulation, or pregnancy-associated hypertension—all requiring urgent evaluation.
Elliptocytes/ovalocytes: hereditary elliptocytosis, iron deficiency
Acanthocytes (spur cells): liver disease, abetalipoproteinemia
Echinocytes (burr cells): uremia, artifact from specimen handling
Teardrop cells: myelofibrosis, severe anemia, thalassemia
Color Abnormalities:
Hypochromia (pale cells): iron deficiency, thalassemia Polychromasia (bluish-gray cells): reticulocytosis, indicating active RBC production
Inclusions:
Howell-Jolly bodies (nuclear remnants): asplenia, severe hemolytic anemia
Basophilic stippling: lead poisoning, thalassemia
Parasites: malaria (Plasmodium species), babesiosis
Both thick and thin blood films should be prepared for optimal parasite detection, with thick films offering superior sensitivity for low-level parasitemia and thin films providing ideal morphology for species identification.
Heinz bodies: G6PD deficiency, oxidative damage
Rouleaux formation: RBCs stacked like coins, seen in multiple myeloma, chronic inflammation
WBC Abnormalities
Quantitative: Leukocytosis (elevated), leukopenia (decreased), or specific increases/decreases in particular cell types
Qualitative: Left shift: immature neutrophils (bands, metamyelocytes), seen in bacterial infection
Blast cells: immature cells suggesting acute leukemia
Atypical lymphocytes: viral infections (especially Epstein-Barr virus)
Toxic granulation: severe infection, inflammation
Döhle bodies: infection, pregnancy
Hypersegmented neutrophils: vitamin B12/folate deficiency
Platelet Abnormalities Giant platelets: immune thrombocytopenia, myeloproliferative disorders
Platelet clumping: may cause falsely low automated counts
Decreased number: thrombocytopenia from various causes
The smear also monitors disease progression and treatment response.
White Blood Cell Morphology
Auer rods, which are a pink-red needle-like cytoplasmic inclusions, which are pathognomonic for acute myelogenous leukemia.
Smudge cells/ruptured lymphocytes strongly suggest chronic lymphocytic leukemia, requiring flow cytometry for confirmation.
Hypogranular, hypolobulated neutrophils are characteristic of myelodysplastic syndromes, particularly when accompanied by macrocytic red cells.
Conversely, hypolobulated neutrophils with large red cells specifically suggest SF3B1-mutant MDS.
Circulating blasts (up to 20%) indicate advanced MDS or acute leukemia, necessitating bone marrow examination.
Dysplastic features in multiple cell lines (dyserythropoiesis, dysgranulopoiesis, dysmegakaryopoiesis) mandates bone marrow aspirate and biopsy with cytogenetic analysis for definitive MDS diagnosis.
Microangiopathic changes require immediate ADAMTS-13 testing, coagulation studies, and renal function assessment to evaluate for thrombotic thrombocytopenic purpura or disseminated intravascular coagulation.
Blast cells or Auer rods require urgent bone marrow examination, flow cytometry, and cytogenetic testing including Philadelphia chromosome analysis.
The morphologic pattern guides molecular testing—for example, ringed sideroblasts prompt SF3B1 mutation analysis in MDS.