The peripheral smear, also known as a peripheral blood film, is a fundamental diagnostic tool in hematology used to visually examine blood cells under a microscope. This simple test involves spreading a small blood sample onto a glass slide to create a thin layer for analysis. Unlike automated blood tests that provide numerical counts, the smear offers a detailed, visual assessment of cell quality, size, shape, and structure. It is invaluable for identifying subtle changes in red blood cells, white blood cells, and platelets that can signal the presence of various diseases.
The Preparation Process
The creation of a high-quality peripheral smear begins with placing a single drop of anticoagulated blood near one end of a clean glass slide. A second slide, called the spreader, is used to draw the blood backward until it spreads across the angle formed between the two slides. The spreader is then pushed forward with one smooth, rapid motion, creating a thin film of blood that tapers off to the feathered edge.
The feathered edge is the most crucial area for microscopic examination because the cells are spread thinly enough to be viewed individually without overlapping. Once the film is air-dried, it undergoes staining, typically using a polychromatic stain such as Wright-Giemsa. The dyes react with different cellular components, like the nucleus and cytoplasm, making them visible and distinguishable under magnification.
Clinical Indications for Ordering
A doctor often orders a peripheral smear when a patient’s automated complete blood count (CBC) shows abnormal values, such as unexplained low or high counts of red cells, white cells, or platelets. The smear provides visual confirmation and morphological context that automated machines cannot offer. For instance, if the CBC flags a low platelet count, the smear can reveal if the low count is real or an artifact caused by platelet clumping.
The smear is used to investigate the cause of anemia, a condition characterized by a deficiency of red blood cells or hemoglobin. Visualizing red blood cell morphology is the quickest way to categorize the type of anemia, such as identifying the microcytic (small) and hypochromic (pale) cells typical of iron deficiency. It also evaluates suspected hemolytic anemias, where red blood cells are prematurely destroyed, by looking for fragmented cells.
The peripheral smear is used in screening for hematological malignancies like leukemia and lymphoma. The presence of immature or abnormal white blood cells, known as blasts, suggests a bone marrow disorder requiring further investigation. It is also essential for infectious disease evaluation, particularly in diagnosing parasitic infections like malaria, where the organism can be seen inside the red blood cells.
Analyzing the Cellular Components
The pathologist or trained medical laboratory scientist systematically examines the stained peripheral smear to assess the three main cellular components of the blood. The analysis focuses on both the number and the morphology (structure) of these cells, providing a comprehensive picture of the body’s hematopoietic health.
Red Blood Cells (RBCs)
The analyst assesses red blood cells for variations in size (anisocytosis), shape (poikilocytosis), and color (reflecting hemoglobin content). Specific shapes offer diagnostic clues; for example, crescent-shaped sickle cells confirm sickle cell disease. Small, dense spherocytes lacking central pallor suggest hereditary spherocytosis or autoimmune destruction.
Fragmented red cells, called schistocytes, signal microangiopathic hemolytic processes, occurring when red cells are sheared by turbulent blood flow or fibrin strands. Other findings include target cells, which appear with a central dot of hemoglobin, often seen in liver disease or thalassemia. Teardrop-shaped cells (dacrocytes) suggest infiltration or scarring of the bone marrow, such as in myelofibrosis. The presence of nucleated red blood cells, normally confined to the bone marrow, indicates a demand for rapid red cell production or severe disruption of the marrow architecture.
White Blood Cells (WBCs)
The examination of white blood cells involves performing a differential count, which determines the percentage of each type of leukocyte. The smear reveals qualitative changes, such as hypersegmented neutrophils (six or more nuclear lobes), a classic finding in megaloblastic anemias caused by B12 or folate deficiency. In severe infection, neutrophils may display toxic granulation (prominent, dark-staining granules) along with cytoplasmic vacuoles.
The smear is also used to identify atypical lymphocytes, which are large, reactive cells seen in viral infections like infectious mononucleosis. The most concerning finding is the presence of blasts, which are immature white blood cells prematurely released from the bone marrow, pointing directly to acute leukemia.
Platelets
Platelet analysis begins with estimating the number of platelets per microscopic field to confirm the automated count and check for clumping. The morphologic assessment focuses on platelet size and granularity. Abnormally large platelets, known as giant platelets or megathrombocytes, can indicate a myeloproliferative disorder or congenital conditions like Bernard-Soulier syndrome.
A reduced amount of internal staining material, resulting in hypogranular platelets, suggests a defect in platelet production often seen in myelodysplastic syndromes. The visual details of these three cell lines allow the peripheral smear to serve as a high-resolution snapshot of the patient’s overall blood health.