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Diagnosis and tests

Blood smear

The numbers from an analyser tell a lot, but they do not show what the cells look like. For that there is an old but still irreplaceable method: the blood smear — looking at a drop of blood on a glass slide under the microscope. This topic explains how a smear is made, what can be seen on it in leukemia and why it is only one step towards a diagnosis.

Last updated: ~6 min read
A thin transparent glass slide on a dark navy background carrying a layer of blood cells glowing softly in violet and pink tones, with gentle light falling from above.
Figure 1.Concept: a drop of blood is stained on a slide, and every cell becomes visible under the microscope.

01Short answer

A blood smear (peripheral blood smear) is a drop of blood spread thinly on a glass slide, stained with a special dye and examined under the microscope. A specialist looks at the size, shape and number of red cells, white cells and platelets, counts the types of white cells and searches for cells that are not normally found in the blood — such as immature blasts. In leukemia the smear gives very valuable clues: blasts in AML and ALL, Auer rods in some cases of AML, many myeloid cells at every stage of maturity in CML, “smudge” cells in CLL, and lymphocytes with thin projections on their surface in hairy cell leukemia. A smear that raises suspicion of acute promyelocytic leukemia (APL) can be a reason to start urgent treatment. Even so, a smear usually does not make the final diagnosis on its own: it is completed by a bone marrow examination, flow cytometry and genetic tests.

02Simple explanation

A blood smear often needs no extra blood draw: a drop from the sample taken for the complete blood count is spread on a slide, dried and stained. A laboratory scientist, pathologist or hematologist then examines it under the microscope.

On a smear the doctor is looking at a kind of “photograph” of the blood: are the cells the normal size and shape, and how many of each type are there? If the numbers answer the question “how many”, the smear answers “what do they look like”.

Blasts are the youngest, most immature forms of blood cells. Normally there are only a few of them in the bone marrow, and they do not enter the blood. Finding blasts in the blood leads the doctor straight to a bone marrow test.

Some types of leukemia have their own “signature” on a smear — for example, in hairy cell leukemia the cells have thin, hair-like projections on their surface. These signatures show the doctor where to look next.

A smear is a quick and informative test, but it is only part of the diagnosis. A final answer usually needs a bone marrow sample and specialised laboratory tests. Do not hesitate to ask your hematologist what was found.

03Scientific explanation

The method: according to MedlinePlus, blood is spread on a slide, stained and examined under the microscope to assess red cells, white cells and platelets. Testing.com notes that most laboratories also use automated digital systems, but in unusual cases the eye of an experienced specialist is decisive. A smear result more often points to the likelihood of a disease and the need for further tests than it makes a final diagnosis by itself.

Blast percentage: according to the ACS, blasts make up no more than 5% of cells in normal bone marrow, and the blood usually contains none. Diagnosing AML generally requires at least 20% blasts in the marrow or blood; with certain diagnostic genetic changes, a lower percentage can be enough. The 2022 WHO classification has removed the blast threshold entirely for many genetically defined types of AML. For ALL, the ACS likewise generally uses at least 20% blasts in the marrow.

Typical findings by type: in AML, myeloblasts and sometimes needle-shaped reddish inclusions in the cytoplasm called Auer rods; in ALL, lymphoblasts; in CML, a high white count with early myeloid cells such as myelocytes; in CLL, many small lymphocytes and “smudge” cells (ACS); and in hairy cell leukemia, cells that look “hairy” (NCI). These findings point the way, while flow cytometry and genetic tests confirm the exact type.

APL — when the smear is urgent: according to the NCI, APL is commonly associated with disseminated intravascular coagulation (DIC), and typical APL cells have cytoplasm densely packed with large granules and bundles of Auer rods. European LeukemiaNet (ELN) recommendations advise starting ATRA (tretinoin) immediately when APL is suspected on clinical and morphological grounds, without waiting for genetic confirmation, together with intensive support for the clotting problem. This is a rare but very important situation in which a smear can save a life.

04What happens in the body?

How is a smear made?

A drop of blood is placed at one end of a slide and spread into a thin, even layer with a second slide. Once it has dried, special stains colour the nucleus and cytoplasm of the cells differently. This takes a few minutes, and the result is often ready the same day.

What does the specialist look at?

The size and shape of red cells, the types and maturity of white cells, and the number and appearance of platelets are all assessed. Particular attention goes to cells that should not be in the blood — blasts and other immature forms. If they are found, their percentage is recorded.

Among many pale red cells on a dark navy background, a few large round cells with deep violet nuclei stand out in a soft glow.
Figure 2.On a smear, the specialist looks for immature blasts among normal cells.

The “signatures” of different leukemias

Each type of leukemia can look different on a smear: in some, blasts with large nuclei dominate; in others, many small lymphocytes; in others still, cells with thin projections on their surface. This picture helps the doctor choose the next tests.

Three different translucent cells side by side on a dark navy background: a round cell with a large nucleus, a small dense lymphocyte and a cell with thin hair-like projections on its surface.
Figure 3.Cells can look different in different types of leukemia — this helps choose the next tests.

What it says about red cells and platelets

A smear looks not only at white cells but also at red cells and platelets. Changes in red cell size and shape help explain the cause of anemia, and the appearance of platelets makes it possible to double-check the number counted by the analyser. So a smear is useful both in the search for leukemia and in telling apart other blood problems.

What happens after the smear?

If the smear shows suspicious changes, the doctor usually orders a bone marrow aspiration and biopsy, flow cytometry and genetic tests. This waiting period can be hard. Asking which tests will be done, when, and roughly when the results will be ready can give you back a sense of control.

05From a drop to a diagnosis

Where the smear fits on the path to a diagnosis — in four steps.

A drop of blood — Taken from the CBC sample and spread on a slide.1A drop of bloodTaken from the CBC sample and spread on a slide.
Staining — Dyes reveal the nucleus and cytoplasm.2StainingDyes reveal the nucleus and cytoplasm.
Microscope — Cell shapes are assessed and blasts looked for.3MicroscopeCell shapes are assessed and blasts looked for.
Next tests — If needed: marrow, flow cytometry, genetics.4Next testsIf needed: marrow, flow cytometry, genetics.
Cell appearanceSize, shape, maturity.
DirectionWhich type of leukemia may be suspected.
UrgencySuspected APL needs immediate treatment.

06What can a smear show? (simplified)

Type of leukemiaTypical smear findingNext step
AMLMyeloblasts, sometimes Auer rodsMarrow, flow cytometry, cytogenetics, molecular tests
APLAbnormal granular promyelocytes, bundles of Auer rodsUrgent treatment and clotting tests, PML::RARA confirmation
ALLLymphoblastsMarrow, flow cytometry (B or T line), genetics
CMLMany white cells at all stages of maturityBCR::ABL1 / Philadelphia chromosome test
CLLMany small lymphocytes, “smudge” cellsFlow cytometry of the blood
Hairy cell leukemiaLymphocytes with thin projectionsFlow cytometry, marrow biopsy, BRAF test

* This table gives a general direction; the picture can differ from person to person, and a smear usually does not make a diagnosis on its own. Discuss your results with your hematologist.

07Key terms

Peripheral blood smear
A drop of blood stained on a slide and examined under the microscope.
Morphology
The size, shape and appearance of cells.
Blast
The youngest, most immature form of a blood cell.
Myeloblast
An immature cell of the myeloid line.
Lymphoblast
An immature cell of the lymphoid line.
Auer rod
A needle-shaped inclusion in the cytoplasm of some myeloid blasts.
Promyelocyte
The stage of myeloid maturation that follows the blast.
Smudge cell
A lymphocyte that looks crushed on a smear; common in CLL.
DIC
Disseminated intravascular coagulation — a risk of both clotting and bleeding.
Cytochemistry
An older method that tells cells apart with chemical stains.

08Key points

  • A smear shows what blood cells look like under the microscope.
  • It is often made from the CBC sample.
  • Blasts are not normally found in the blood.
  • A 20% blast threshold is generally used for AML and ALL.
  • Each type of leukemia can have its own “signature” on a smear.
  • Suspected APL is a reason for urgent treatment.
  • A smear usually does not make the final diagnosis on its own.
  • Next steps: bone marrow, flow cytometry and genetic tests.

09Frequently asked questions

Do I need to give blood again for a smear?

Usually not. A smear is normally made from the sample taken for the complete blood count. Sometimes a repeat smear is needed — for example, to see how things change.

Blasts were found on my smear. Is it definitely leukemia?

Blasts in the blood are a serious sign that needs prompt investigation, but the diagnosis is usually confirmed by a bone marrow sample and specialised tests. In rare cases, young cells can appear in the blood for other reasons.

How quickly will I get the result?

A smear is a quick test and is often reviewed within a day. In urgent cases a doctor can look at it within a few hours.

Why is treatment for APL started so quickly?

In APL the clotting system can be seriously disturbed, which raises the risk of bleeding. That is why experts recommend starting treatment as soon as APL is suspected, without waiting for genetic confirmation. This is one of the main reasons for the good results in APL.

Can a smear tell the exact type of disease?

A smear gives strong clues, but the exact type and subtype are usually determined by flow cytometry, cytogenetics and molecular tests.

Is the smear repeated during treatment?

Yes, sometimes. During treatment a smear helps show whether blasts have cleared from the blood and whether cells are recovering. But the main assessment of response is usually made with bone marrow and MRD tests.

10Questions for your doctor

Take these questions to your appointment. The ones you save are collected on the “My questions” page and stay on this device only.

  1. Were blast cells seen on the blood smear?

  2. What other changes were found on the smear?

  3. Which further tests does the smear result call for?

  4. When should the smear be repeated?

My questions

12Sources

  1. MedlinePlus (U.S. National Library of Medicine). Blood Smear
  2. MedlinePlus (U.S. National Library of Medicine). Blood Differential
  3. National Cancer Institute (NCI). NCI Dictionary of Cancer Terms: peripheral blood smear
  4. National Cancer Institute (NCI). NCI Dictionary of Cancer Terms: blast
  5. National Cancer Institute (NCI). Adult Acute Myeloid Leukemia Treatment (PDQ®) — Health Professional Version
  6. National Cancer Institute (NCI). Hairy Cell Leukemia Treatment (PDQ®) — Patient Version
  7. American Cancer Society. Tests for Acute Myeloid Leukemia (AML)
  8. American Cancer Society. Tests for Acute Lymphocytic Leukemia
  9. American Cancer Society. Tests for CML
  10. American Cancer Society. Tests for CLL
  11. Testing.com. Blood Smear Test: What It Shows and What Results Mean
  12. Blood (American Society of Hematology), 2019. Management of acute promyelocytic leukemia: updated recommendations from an expert panel of the European LeukemiaNet
  13. Leukemia, 2022. The 5th edition of the World Health Organization Classification of Haematolymphoid Tumours: Myeloid and Histiocytic/Dendritic Neoplasms
Medical disclaimerThis information is for educational purposes only and does not replace medical advice.
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