A peripheral blood smear — also called a blood film — is a test in which a drop of blood is spread across a glass slide, stained, and examined under the microscope by a pathologist or a trained laboratory technician. It is one of the oldest tests in laboratory medicine and remains one of the most informative. While automated machines used for the complete blood count (CBC) can count and measure blood cells very accurately, they cannot reliably describe how those cells look. The smear allows the cells themselves to be examined directly.
A blood smear is usually performed as a follow-up to an abnormal CBC or when specific abnormalities are suspected based on symptoms or other test results. It can detect changes that automated counters miss, identify abnormal or immature cells, and provide clues that point toward specific diagnoses. This article explains what the test involves, what the pathologist looks for, what common findings mean, and what may need to happen next.
The findings shown on your report depend on what the pathologist sees on your specific slide. The findings discussed in this article are common examples, not a complete list, and the significance of any given finding depends on the rest of your blood test results and your clinical history. Always discuss your report with your doctor, who can interpret the findings in the context of your symptoms, medical history, and other tests.
What is a peripheral blood smear?
The word peripheral in this context simply means circulating in the bloodstream — as opposed to the bone marrow, where blood cells are made. A peripheral blood smear, therefore, is an examination of the cells circulating in the blood.
To make the smear, a small drop of blood is placed near one end of a glass slide, and a second slide is used to spread the blood into a thin, even film. The slide is then stained with a special dye (most often a Wright-Giemsa stain) that colors different parts of the cell different shades, making the features inside each cell easier to see. Once stained, the slide is examined under a microscope.
The smear contains all three types of cells found in the blood:
- Red blood cells — the most numerous cells in the blood. They carry oxygen from the lungs to the rest of the body. Their size, shape, color, and contents are all examined on the smear.
- White blood cells — the cells of the immune system. The smear shows the different types of white blood cells and can identify abnormal or immature cells.
- Platelets — tiny cell fragments that help the blood clot. The smear is used to estimate platelet numbers and identify abnormal platelets.
The pathologist examines each of these cell types in turn, looking for anything that falls outside the normal range of appearance.
Why is a blood smear done?
A peripheral blood smear is usually performed for one of the following reasons:
- To follow up an abnormal CBC. When the automated CBC shows an unusual result — a very high or low cell count, a laboratory equipment flag, or a measurement that does not fit the clinical picture — a smear is examined to assess the cells directly. This is the most common reason a smear is performed.
- To investigate suspected blood disorders. A smear is often ordered when the doctor suspects a specific condition, such as anemia of unclear cause, a clotting disorder, possible leukemia, or a viral infection like mononucleosis. The appearance of the cells often gives important clues.
- To detect immature or abnormal cells. Cells such as blasts (very early blood-forming cells), nucleated red blood cells, and atypical lymphocytes are normally not present in the blood and are not always reliably flagged by automated equipment. A smear can identify them and describe how they look.
- To confirm or interpret automated findings. Some results from automated equipment — such as flags suggesting platelet clumping or unusual cells — need to be confirmed by examining a slide before they can be reported accurately.
- To monitor known conditions. In patients with chronic blood disorders such as sickle cell disease, thalassemia, or chronic leukemia, the smear may be examined at regular intervals to monitor cell appearance over time.
In some cases, the smear is reviewed by a laboratory technician, and the findings are reported in a single short comment. In other cases — particularly when significant abnormalities are seen — the slide is reviewed by a pathologist, and a detailed description appears on the report.
How is the test performed?
A blood smear uses the same blood sample that was collected for the CBC, so no additional blood draw is needed. In the laboratory, a drop of blood is placed on a clean glass slide. A second slide is held at an angle and drawn smoothly across the first, spreading the blood into a thin film. The slide is allowed to air-dry, then stained.
Most laboratories use an automated stainer to apply the stain consistently from slide to slide, but the principle is the same regardless of the method: the stain colors different parts of the cells different shades. Nuclei (the part of the cell that holds DNA) typically appear blue or purple, while the surrounding cytoplasm appears pink, red, or pale blue depending on the cell type. Color differences allow each cell type to be identified.
The pathologist or laboratory technician then examines the slide under the microscope, working through a small area where the cells are spread out in a single layer. The cells are examined for their numbers, sizes, shapes, colors, and internal contents. A typical careful review covers many hundreds of cells.
Results are usually available within a few hours to a day. In urgent situations — such as when an automated counter has flagged the possible presence of blasts — the smear may be examined and reported the same day.
What does the pathologist look at?
The findings on a blood smear are organized by cell type. Each of the three main cell groups is examined separately, and the report typically mentions any noteworthy features within each group. The sections below describe the most common findings.
Red blood cell findings
Normal red blood cells are small, round, and flat, with a pale center. They appear pink under the microscope after staining. The pathologist looks at four main features of the red blood cells:
- Size. Red blood cells that are larger than normal are called macrocytic; cells smaller than normal are called microcytic. A mixture of different sizes is called anisocytosis. Size variation often points to a specific cause of anemia — for example, macrocytic cells are seen in vitamin B12 or folate deficiency, while microcytic cells are characteristic of iron deficiency anemia.
- Shape. A mixture of abnormally shaped cells is called poikilocytosis. Specific shapes can point to specific conditions and are described below.
- Color. The amount of hemoglobin (the protein that carries oxygen) determines how dark the cells appear. Pale-looking cells are called hypochromic and are common in iron deficiency. Cells that look slightly blue-gray are called polychromatic and are usually young red blood cells recently released from the bone marrow.
- Inclusions. These are particles or structures inside the red blood cells. Several types are described below and can point to specific causes.
Common specific red blood cell findings include:
- Microcytic, hypochromic cells — small, pale red blood cells. Most often seen in iron deficiency anemia and in the inherited hemoglobin disorder thalassemia.
- Macrocytic cells — larger-than-normal red blood cells. Seen in vitamin B12 or folate deficiency, liver disease, hypothyroidism, and some bone marrow disorders.
- Target cells — red blood cells with a dark center inside a pale ring, giving them the appearance of an archery target. Seen in liver disease, thalassemia, hemoglobin C disease, and after removal of the spleen.
- Spherocytes — small, round red blood cells without the normal pale center. Seen in hereditary spherocytosis (an inherited condition) and in autoimmune hemolytic anemia (in which the immune system destroys red blood cells).
- Schistocytes — red blood cell fragments with sharp, irregular edges. Their presence is an important finding because it usually indicates that red blood cells are being mechanically broken apart in the small blood vessels, as can occur in conditions such as thrombotic thrombocytopenic purpura (TTP), hemolytic uremic syndrome (HUS), disseminated intravascular coagulation (DIC), or with mechanical heart valves.
- Sickle cells — red blood cells shaped like a crescent or sickle, caused by abnormal hemoglobin polymerizing inside the cell. Their presence is characteristic of sickle cell disease, an inherited hemoglobin disorder.
- Teardrop cells (dacrocytes) — red blood cells shaped like a teardrop or pear. Seen in bone marrow disorders that cause scarring of the marrow, including primary myelofibrosis, and in some types of severe anemia.
- Nucleated red blood cells — red blood cells that still contain a nucleus. These are normally found only in the bone marrow. Their appearance in the blood may indicate the bone marrow is under significant stress (severe anemia, infection, marrow infiltration) or may be a normal finding in newborns.
- Howell-Jolly bodies — small dark dots inside red blood cells, representing leftover fragments of nuclear material. Commonly seen after removal of the spleen, in functional loss of the spleen (as occurs in sickle cell disease), and in some bone marrow disorders.
- Basophilic stippling — tiny dark blue dots scattered throughout the red blood cell. May suggest lead poisoning, certain inherited anemias, or other bone marrow disorders.
- Polychromasia — red blood cells that look slightly blue-gray. These are young red blood cells just released from the bone marrow. An increase in polychromasia suggests that the bone marrow is producing red blood cells more rapidly than usual, which is expected after blood loss or in conditions in which red blood cells are being destroyed.
- Rouleaux — red blood cells stacked together like a roll of coins. May be seen in inflammatory conditions, and is particularly associated with high levels of certain proteins in the blood, as occurs in multiple myeloma.
White blood cell findings
The blood smear allows the different types of white blood cells to be identified and counted individually. This is the basis of the manual differential — the part of the test that provides the percentages and absolute counts for each white blood cell type. The article on understanding your white blood cell differential covers each of the five main white blood cell types in detail.
Beyond simply counting the cells, the pathologist examines how each one looks. Common white blood cell findings include:
- Left shift — an increase in immature neutrophils released from the bone marrow before they are fully mature. The most common immature form is the band neutrophil, a slightly less mature stage. A left shift is typical of bacterial infection and acute inflammation, although it can also occur in pregnancy, after surgery, or with bone marrow disorders.
- Toxic granulation, Döhle bodies, and vacuoles — changes inside neutrophils that suggest they are responding to a severe infection or inflammation. These features support the impression of an active, serious infection.
- Hypersegmented neutrophils — neutrophils whose nuclei have an unusually large number of segments (typically more than five lobes). Often seen in vitamin B12 or folate deficiency.
- Atypical lymphocytes — lymphocytes with unusual size, shape, or staining. Most commonly seen in viral infections, especially mononucleosis caused by Epstein-Barr virus. Atypical lymphocytes can sometimes also be seen in lymphoid cancers, and additional testing may be needed to distinguish between these possibilities.
- Plasma cells — antibody-producing cells that are normally found in the bone marrow and tissues but not in the blood. Their appearance in the blood may be seen in some viral infections and, less commonly, in plasma cell cancers such as plasma cell leukemia.
- Blasts — the earliest, most immature blood-forming cells. Blasts are normally found only in the bone marrow. The presence of blasts in the blood is always abnormal and may indicate acute myeloid leukemia, acute lymphoblastic leukemia, or another bone marrow disorder. Blasts in the blood usually prompt urgent further investigation, often including a bone marrow biopsy.
- Promyelocytes, myelocytes, and metamyelocytes — intermediate stages between blasts and mature neutrophils. Their presence in the blood, particularly in combination with other findings, may suggest chronic myeloid leukemia, a severe response to infection, or a bone marrow disorder.
- Smudge cells — fragile lymphocytes that break apart when the smear is made, leaving behind a flattened, smudged appearance. They are a characteristic finding in chronic lymphocytic leukemia.
- Hairy cells — lymphocytes with fine, hair-like projections from their surface. Their presence is characteristic of hairy cell leukemia.
- Auer rods — needle-shaped red structures inside the cytoplasm of some blasts. They are highly specific for acute myeloid leukemia.
Platelet findings
Platelets normally appear as small purple specks scattered across the slide. The pathologist examines them for both their numbers and their appearance:
- Platelet estimate — a rough check on whether the platelet count appears appropriate. If the platelet count from the automated CBC seems unexpectedly high or low, comparing it to the visual estimate on the smear can confirm or refute the result.
- Platelet clumping — platelets sticking together to form clumps. This is usually a laboratory artifact, in which the platelets clump together inside the collection tube and are then counted incorrectly by the automated machine, producing a falsely low result called pseudothrombocytopenia. Repeating the test using a different anticoagulant in the tube usually resolves the problem.
- Giant platelets — platelets that are larger than usual, sometimes nearly as large as a red blood cell. May be seen when the bone marrow is rapidly producing new platelets (such as after major bleeding or in response to low platelet counts), and in some inherited platelet disorders and bone marrow conditions.
- Reduced platelet number — fewer platelets than expected on the smear. May indicate a true low platelet count (called thrombocytopenia), which has many possible causes including immune destruction, certain medications, viral infections, and bone marrow disorders.
What happens after a blood smear?
The findings on a blood smear are interpreted together with the CBC, the differential, your symptoms, your medical history, and any other relevant tests. The smear is rarely a complete diagnosis on its own — it is a piece of information used to point toward the most likely cause of a problem and to guide what should happen next. Depending on the findings, your doctor may:
- Take no further action. Many smear findings are mild, expected for the clinical situation, or non-specific. If the smear confirms what was already suspected (for example, the typical features of iron deficiency in a patient already known to have low iron stores), no additional testing may be needed.
- Repeat the test. Some findings may resolve on their own or be related to a temporary condition. A repeat smear or CBC after a few weeks may be all that is needed.
- Order additional blood tests. The smear findings may suggest specific tests — iron studies, vitamin B12 and folate levels, viral testing for mononucleosis or HIV, hemoglobin testing for sickle cell disease or thalassemia, and others — to confirm a suspected cause.
- Order flow cytometry. If the smear shows abnormal lymphocytes or blasts, flow cytometry can identify the specific cell type and help distinguish conditions such as chronic lymphocytic leukemia, acute leukemia, and reactive changes due to infection.
- Refer to a hematologist. Findings suggesting a primary blood disorder — particularly the presence of blasts, persistent abnormal cells, or severe abnormalities in more than one cell line — usually prompt referral to a specialist in blood diseases.
- Perform a bone marrow biopsy. If the smear suggests a serious bone marrow disorder, a bone marrow biopsy is often the next step. This procedure samples the bone marrow directly, so the cells can be examined where they are produced, rather than after they enter the bloodstream.
An important point to keep in mind is that many smear findings are non-specific. The same finding — for example, a few schistocytes or some polychromasia — can be seen in many different conditions, and the meaning depends on what else is going on. Your doctor is the best person to put the smear findings into context.
Questions to ask your doctor
- Why was a blood smear performed on my sample?
- Were any abnormal cells or unusual features described on my smear?
- What do these findings suggest about the cause of my symptoms or my abnormal blood counts?
- Are the findings consistent with a condition I already have, or do they suggest something new?
- Could any of my medications be affecting the appearance of my blood cells?
- Do I need any additional blood tests based on what was seen on the smear?
- Should I have flow cytometry or other specialized testing?
- Do I need to be referred to a hematologist?
- Should the smear be repeated, and if so, when?
- If blasts or other abnormal cells were seen, do I need a bone marrow biopsy?
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