A blood smear is often used as a follow-up test to abnormal results on a complete blood count (CBC) to evaluate the different types of blood cells. It may be used to help diagnose and/or monitor numerous conditions that affect blood cell populations.

For the test, a drop of blood is spread thinly onto a glass slide that is then treated with a special stain. Traditionally, trained laboratorians have examined blood smears manually using a microscope. More recently, automated digital systems have become available to help analyze blood smears more efficiently.

At one time, a blood smear was prepared on nearly everyone who had a CBC. With the development of more sophisticated, automated blood cell counting instruments, it has now become routine to provide an automated differential. However, if the results from an automated cell count and/or differential indicate the presence of abnormal white blood cells (WBCs), red blood cells (RBCs), and/or platelets or if there is reason to suspect that abnormal cells are present, then a blood smear will be performed.

A blood smear is often used to categorize and/or identify conditions that affect one or more type of blood cells and to monitor individuals undergoing treatment for these conditions. There are many diseases, disorders, and deficiencies that can affect the number and type of blood cells produced, their function, and their lifespan. Examples include anemia, myeloproliferative neoplasms, bone marrow disorders, and leukemia.

Usually, only normal, mature or nearly mature cells are released into the bloodstream, but certain circumstances can induce the bone marrow to release immature and/or abnormal cells into the circulation. When a significant number or type of abnormal cells are present, it can suggest a disease or condition and prompt a health practitioner to do further testing. Depending on the findings from a CBC and blood smear, follow-up testing may include tests such as:

• Iron tests
• Vitamin B12 and folate tests
• Flow cytometry immunophenotyping
• Bone marrow aspiration and biopsy
• BCR-ABL1
• Hemoglobinopathy evaluation

The blood smear is primarily ordered to evaluate blood cells when a CBC with differential, performed with an automated blood cell counter, indicates the presence of abnormal or immature cells. It may also be performed when a person has signs and symptoms that suggest a condition affecting blood cell production or lifespan.

Examples of signs and symptoms that may indicate one of these blood disorders include:

• Weakness, fatigue
• Pale complexion
• Unexplained jaundice
• Fever
• Excessive bleeding episodes, easy bruising, or frequent nose bleeds
• Enlargement of the spleen
• Bone pain

A blood smear may also be ordered on a regular basis when a person is being treated or monitored for a blood cell-related disease.

Findings from a blood smear evaluation are not always diagnostic in themselves and more often indicate the presence of an underlying condition, its severity, and the need for further diagnostic testing. The results are taken into consideration with the results of the CBC and other laboratory tests as well as the tested person's clinical signs and symptoms.

The results of a blood smear typically include a description of the appearance of the red blood cells, white blood cells, and platelets as well as any abnormalities that may be seen on the slide. 

Red Blood Cells (RBCs)
Normal, mature red blood cells are uniform in size (7-8 µm in diameter) and do not have a nucleus as most other cells do. They are round and flattened like a donut with a depression in the middle instead of a hole (biconcave). Due to the hemoglobin inside the RBCs, they appear pink to red in color with a pale center after staining the blood smear. When the appearance of RBCs (RBC morphology) is normal, it is often reported as normochromic and normocytic.

While not every RBC will be perfect, any significant number of cells that are different in shape or size may indicate the presence of disease. Some examples of conditions that can affect red blood cells include:

• Anemia
• Hemoglobin variants including sickle cell anemia and thalassemia
• Leukemia
• Myeloproliferative or myelodysplastic neoplasms
• Bone marrow disorders

There may be one or more RBC irregularities seen on a blood smear. Two examples include:

• Anisocytosis — variable sizes of red blood cells may indicate anemia; RBCs smaller than normal are referred to as microcytes and RBCs larger than normal are called macrocytes.
• Poikilocytosis — various shapes of red cells; these may include echinocytes, acanthocytes, elliptocytes, keratocytes, rouleaux, sickle cells, target cells, teardrop cells, and shistocytes.

More detail on RBCs

White Blood Cells (WBCs)
As part of a blood smear evaluation, a manual WBC differential is performed. Typically, at least 100 WBCs are found, counted, and categorized according to type. The percentage of each type is calculated. In addition, the appearance (morphology) and stage of development of the WBCs are noted. White blood cells have a nucleus surrounded by cytoplasm. All WBCs are derived from bone marrow stem cells. In the bone marrow, they differentiate into two groups: granulocytic and lymphoid cells. They mature into five distinct types of WBCs.

Those with granules in their cytoplasm are also called granulocytes and include:

• Neutrophils (10-18 µm) are cells that have cytoplasm with pink or purple granules. They compose the majority of WBCs in a healthy adult. They are involved in the defense against infections.
• Eosinophils (10-15 µm) are easily recognized in stained smears with their large, red-orange granules. Generally low in number (1-3%), they most often increase in number in individuals with allergies and parasitic infections.
• Basophils (10-15 µm) have large, black granules and are the least often seen type of WBC (1%).

The non-granulocytes include: 

• Monocytes are usually the largest of the WBCs (12-20 µm) and are often referred to as scavenger cells (phagocytes). They can ingest particles such as cellular debris, bacteria, or other insoluble particles.
• Lymphocytes are smaller in size (10-12 µm) and have a small amount of cytoplasm and often a smooth, round nucleus. One type of lymphocyte, the B-cell, is responsible for the production of antibodies (immunoglobulins).

Numerous diseases and conditions can affect the absolute or relative number of WBCs and their appearance on a blood smear. Examples of some of the conditions include:

• Infections and/or inflammation — can increase certain types of WBCs
• Bone marrow disorders — depending on the condition, may increase or decrease absolute and relative numbers of WBCs
• Allergies — may affect the number of eosinophils
• Leukemia or myelodysplastic or myeloproliferative neoplasm — immature white blood cells such as blasts may be seen on the blood smear; blasts are normally found in the bone marrow where WBCs are produced and mature before being released into the blood. If blasts are seen on a blood smear, they may indicate a serious bone marrow disease.

More detail on WBCs

Platelets
These are cell fragments that develop from large bone marrow cells called megakaryocytes. Upon release from the bone marrow, they appear as fragments in the peripheral blood. When there is blood vessel injury or other bleeding, the platelets become activated and begin to clump together to form aggregates, which is the beginning of a blood clot.

There must be a sufficient number of platelets to control bleeding. If there are too few, of if they don't function properly, the ability to form a clot becomes impaired and can be a life-threatening situation. In some people, too many platelets may be produced, which may result in interferences with the flow of blood, increasing a person's risk of developing a blood clot. These same people may also experience bleeding because many of the extra platelets may be dysfunctional even though they appear normal.

A platelet count is usually part of a CBC. An abnormally low number or high number of platelets may be further evaluated by preparing a blood smear to directly visualize any anomalies in shape or size. For example, large platelets or giant platelets may be seen in myeloproliferative neoplasms or immune thrombocytopenia, a condition in which the immune system inappropriately produces antibodies directed against platelets. (For more information, see the articles on Platelet Disorders and Excessive Clotting Disorders.)

Findings on a blood smear that are abnormal are typically referred to a pathologist, often one with extensive experience in the study of blood (hematology), for further review and interpretation. Depending on the results, follow-up testing involving an examination of a bone marrow aspirate and biopsy may be required for a diagnosis.

Blood smears may be used to help diagnose malaria, a disease caused by a blood parasite. The parasite may be seen when a blood smear is examined under a microscope. Malaria rarely occurs in the U.S. and is usually only seen in travelers returning from areas where the parasite is more common (endemic). Therefore, the blood smear is not often used for this purpose in the U.S.

Some examples of situations or conditions that may affect or invalidate results of a blood smear include:

• Recent blood transfusion
• Elevated levels of protein

Values can fluctuate at times of illness or stress; intense exercise or smoking can also affect cell counts.