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White Blood Cell (WBC) Differential

  • Why Get Tested?

    To help determine the cause of abnormal results on a white blood cell (WBC) count; to help diagnose and/or monitor an illness affecting your immune system, such as an infection or inflammatory condition, or cancers that affect your white blood cells, such as leukemia or lymphoma

    When To Get Tested?

    When you have a complete blood count (CBC) done as part of a routine health examination; when results of a CBC fall outside the reference range; when you have  signs and symptoms related to a condition affecting white blood cells, such as infection, inflammation, or cancer; when you are receiving treatment that is known to affect WBCs, such as chemotherapy

    Sample Required?

    A blood sample drawn from a vein or blood collected by a pricking a fingertip (fingerstick) or the heel of an infant (heelstick)

    Test Preparation Needed?

    None

  • What is being tested?

    White blood cells (WBCs), also called leukocytes, are cells that circulate in the blood and the lymphatic system that help protect the body against infections. They are an important part of the body's immune system and also have a role in inflammation, allergies, and protection against cancer. A WBC differential categorizes the numbers of each of the different types of WBCs in sample of your blood.

    There are five main types of white blood cells, each with different functions. The differential shows if:

    • The different types of WBCs are present in normal proportion to one another
    • The numbers of the different cell types are normal, increased or decreased
    • Abnormal and/or immature WBCs are present

    This information is helpful in diagnosing specific types of illnesses that affect the immune system and the bone marrow.

    A differential may be performed along with or following a complete blood count (CBC), a test often used as a general health check, or it may be performed in follow-up to abnormal results on a CBC. Most often, a differential is performed on an automated blood analyzer. Occasionally, it is performed manually by a trained laboratory professional who examines a blood smear using a microscope. 

    Types of White Blood Cells

    The bone marrow produces five main types of WBCs, neutrophils, lymphocytes, monocytes, eosinophils, and basophils.

    • Neutrophils (neu) normally make up the largest number of circulating WBCs. They move into an area of damaged or infected tissue, where they engulf and destroy bacteria or sometimes fungi.
    • Lymphocytes (lymphs) exist in both the blood and the lymphatic system. They are broadly divided into three types, but the differential does not distinguish among them. The differential counts and reports all lymphocytes together. Separate specialized testing (like immunophenotyping) must be done to differentiate the three types:
      • B lymphocytes (B cells) are produce antibodies that help protect against infections. Plasma cells are fully differentiated B-cells that produce antibodies, immune proteins that target and destroy bacteria, viruses and other "non-self" foreign antigens.
      • T lymphocytes (T cells) finish maturing in the thymus and consist of a few different types. Some T cells help the body distinguish between "self" and "non-self" antigens. Others initiate and control the extent of an immune response, boosting it as needed and then slowing it as the condition resolves. Other types of T cells directly attack and neutralize virus-infected or cancerous cells.
      • Natural killer cells (NK cells) directly attack and kill abnormal cells such as cancer cells or those infected with a virus.
    • Monocytes (mono), similar to neutrophils, move to an area of infection and engulf and destroy bacteria. They are associated more often with long-term (chronic) rather than acute infections. They are also involved in tissue repair and other functions involving the immune system.
    • Eosinophils (eos) respond to infections caused by parasites, play a role in allergic reactions (hypersensitivities), and control the extent of immune responses and inflammation.
    • Basophils (baso) usually make up the fewest number of circulating WBCs and are thought to be involved in allergic reactions.

    What does a differential tell you?

    A WBC differential can give clues about your condition or what is causing a low or high WBC count. When there is an infection or an inflammatory process somewhere in the body, the bone marrow produces more WBCs, releasing them into the blood. Depending on the cause of infection or inflammation, one particular type of WBC may be increased as opposed to other types. As the condition resolves, the bone marrow produces fewer of that type of WBC and the number drops back to normal levels.

    In addition to infections and inflammation, there are a variety of conditions that can affect the production of WBCs by the bone marrow or their survival in the blood, resulting in either increased or decreased numbers. The differential, along with the other components of the CBC, alerts the healthcare provider to possible health issues. Results are often interpreted along with additional tests such as a blood smear exam, which can show the presence of abnormal and/or immature WBCs.

    In a few serious diseases, some immature forms of the cells are released from the bone marrow into the circulation and may be detected by the WBC differential. This may occur with bacterial infection, leukemia, myelodysplastic syndrome, or myeloproliferative neoplasms, for example. Some immature cells that may be detected include metamyelocytes, myelocytes, promyelocytes, and/or blasts.

    If results indicate a problem, a wide variety of other tests may be performed in order to help determine the cause. A healthcare provider will typically consider your signs and symptoms, medical history, and results of a physical examination to decide what other tests may be necessary. For example, as needed, a bone marrow biopsy might be performed because that is where WBCs normally are produced and where they mature.

  • How is the test used?

    The white blood cell differential is often used as part of a complete blood count (CBC) as a general health check. (This testing is sometimes called CBC with differential or CBC with diff for short.)

    A WBC differential may be used to help diagnose the cause of a high or low white blood cell (WBC) count results seen on a CBC. It may also be used to help diagnose and/or monitor other diseases and conditions that affect one or more different types of WBCs. Some examples of these conditions include:

    • Infections caused by bacteria, viruses, fungi or parasites
    • Inflammation
    • Allergies, asthma
    • Immune disorders (e.g., autoimmune disorders, immune deficiency)
    • Leukemia (e.g., chronic myeloid leukemia, chronic lymphocytic leukemia)
    • Myelodysplastic syndrome
    • Myeloproliferative neoplasms (e.g., myelofibrosis)

    When is it ordered?

    You may have a complete blood count (CBC) and WBC differential (CBC with diff) when you go for a routine health exam.

    A differential is typically included as part of the CBC and is particularly important when you have general signs and symptoms of an infection and/or inflammation, such as:

    • Fever, chills
    • Body aches, pain
    • Headache
    • A variety of other signs and symptoms, depending on the site of suspected infection or inflammation

    Testing may be performed when you have signs and symptoms that your healthcare provider thinks may be related to a blood and/or bone marrow disorder, autoimmune disease or other immune disorder.

    If a differential is not done at the same time as a CBC, it may be ordered when results from the CBC are not within the reference ranges.

    What does the test result mean?

    WBC differential results indicate the number and/or the percentage of each type of white blood cell that is present in your sample of blood at the time of the test.

    Results of a differential are usually reported as absolute values of the five types of WBCs and/or may be reported as a percent of the total number of WBCs. Absolute values are calculated by multiplying the total number of WBCs by the percentage of each type of white cell. In adults, neutrophils typically make up the highest number of WBCs, followed by lymphocytes, then monocytes, eosinophils and basophils. In young children, lymphocytes are often more numerous than neutrophils.

    When interpreting your results of a differential, your healthcare provider will consider several factors, including your signs and symptoms and medical history as well as how high or low each type of WBC is and whether the increase or decrease persists. 

    • A number of factors can cause a temporary rise or drop in the number of any one type of WBC. A persistent increase or decrease will usually prompt your healthcare practitioner to order more testing to determine the cause.
    • A result that is barely outside the reference range may or may not be significant for you while a large rise or drop in one or more types of WBCs usually prompts more testing.

    The following table gives some examples of what results might mean:

    Possible Causes of High and Low WBC Differential Results

    Type of WBC Reference Range2 Examples of causes of a high count Examples of causes of a low count
    Neutrophils (Absolute neutrophil count, percent neutrophils)

    Conventional Units

    Percent: 40-70% 

    Absolute count (per microliter): 
    1800-7800

    SI Units

    Mean number fraction: 0.56 

    Absolute count X 109 per liter:
    1.8-7.8 

    		 Known as neutrophilia
    • Acute bacterial infections and also some infections caused by viruses and fungi
    • Inflammation (e.g., inflammatory bowel disease, rheumatoid arthritis)
    • Tissue death (necrosis) caused by trauma, major surgery, heart attack, burns
    • Physiological (stress, rigorous exercise)
    • Smoking
    • Pregnancy—last trimester or during labor
    • Chronic leukemia (e.g., myelogenous leukemia)
    		 Known as neutropenia
    • Myelodysplastic syndrome
    • Severe, overwhelming infection (e.g., sepsis--neutrophils are used up)
    • Reaction to drugs (e.g., penicillin, ibuprofen, phenytoin, etc.)
    • Autoimmune disorder
    • Chemotherapy
    • Cancer that spreads to the bone marrow
    • Aplastic anemia
    Lymphocytes (Absolute lymphocyte count, percent lymphocytes

    Conventional Units

    Percent 22-44%
    Absolute count (per microliter):
    1000-4800

    SI Units

    Mean number fraction: 0.34
    Absolute count X 109 per liter: 
    1.0-4.8

    		 Known as lymphocytosis Known as lymphopenia or lymphocytopenia
    • Autoimmune disorders (e.g., lupus, rheumatoid arthritis)
    • Infections (e.g., HIV, TB, hepatitis, influenza)
    • Bone marrow damage (e.g., chemotherapy, radiation therapy)
    • Immune deficiency
    Monocytes (Absolute monocyte count, percent monocytes)

    Conventional Units

    Percent 0-7%
    Absolute count (per microliter)
    0-800

    SI Units

    Mean number fraction 0.04
    Absolute count X 109 per liter 
    0-0.80

    		 Known as monocytosis
    • Chronic infections (e.g., tuberculosis, fungal infection)
    • Infection within the heart (bacterial endocarditis)
    • Collagen vascular diseases (e.g., lupus, scleroderma, rheumatoid arthritis, vasculitis)
    • Inflammatory bowel disease
    • Monocytic leukemia
    • Chronic myelomonocytic leukemia
    • Juvenile myelomonocytic leukemia
    		 Known as monocytopenia

    Usually, one low count is not medically significant.

    Repeated low counts can indicate:

    • Bone marrow damage or failure
    • Hairy-cell leukemia
    Eosinophils (Absolute eosinophil count, percent eosinophils)

    Conventional Units

    Percent 0-4%
    Absolute count (per microliter)
    0-450

    SI Units

    Mean number fraction 0.027
    Absolute count X 109 per liter
    0-0.45

    		 Known as eosinophilia
    • Asthma, allergies such as hay fever
    • Drug reactions
    • Inflammation of the skin (e.g., eczema, dermatitis)
    • Parasitic infections
    • Inflammatory disorders (e.g., celiac disease, inflammatory bowel disease)
    • Certain malignancies/cancers
    • Hypereosinophilic myeloid neoplasms
    		 Known as eosinopenia

    This is often difficult to determine because numbers are normally low in the blood. One or an occasional low number is usually not medically significant.
    Basophils (Absolute basophil count, percent basophils)

    Conventional Units

    Percent 0-2%
    Absolute count (per microliter)
    0-200

    SI Units

    Mean number fraction 0.030
    Absolute count X 109 per liter
    0-0.20

    		 Known as basophilia
    • Rare allergic reactions (e.g., hives, food allergy)
    • Inflammation (rheumatoid arthritis, ulcerative colitis)
    • Some leukemias (e.g., chronic myeloid leukemia)
    		 Known as basopenia

    As with eosinophils, numbers are normally low in the blood; usually not medically significant.

    1 from Wintrobe's Clinical Hematology. 14th ed. Greer J, editor. Philadelphia, PA: Wolters Kluwer: 2019.

    In certain cases, immature and/or abnormal cells may be present in the blood and may be detected with a differential. Immature cells include metamyelocytes, myelocytes, promyelocytes, and/or blasts. Additional testing (e.g., bone marrow biopsy) may be necessary.

    My complete blood count (CBC) report includes a result for immature granulocytes (IG). What are they?

    Some automated hematology analyzers report the total number of immature granulocytes (IG) present in a person's blood sample. Immature granulocytes are white blood cells that have not fully developed before being released from the bone marrow into the blood. They may include metamyelocytes, myelocytes, and promyelocytes. These cells are normally only present in the bone marrow because they are precursors of neutrophils, the predominant type of white cells in blood. The presence of immature granulocytes in the blood may occur in various diseases, such as infection or a blood cancer, and thus will often prompt further investigation, which may include additional laboratory testing.

    Can a white blood cell (WBC) differential be performed on samples other than blood?

    Yes. WBC differentials, along with WBC counts, may be performed on many different types of body fluids. A common reason that this is done is to more directly assess one area of the body that may be infected or inflamed. For example, if meningitis is suspected, then a WBC count plus differential may be performed on a sample of cerebrospinal fluid (CSF). Many other examples are listed in the article on Body Fluid Analysis.

    If I have an abnormal result on my WBC differential, what other tests might my healthcare provider order?

    Other general tests to check your health may include a comprehensive metabolic panel (CMP). Depending on your signs, symptoms, medical history, physical exam and suspected condition, your healthcare provider may choose to order a variety of other tests. A few general examples include:

    • Bacterial infection: a culture of the affected area (e.g., urine culture, sputum culture, blood culture), strep test

    • Viral infection: tests for mononucleosis, Epstein-Barr virus

    • Inflammation: C-reactive protein, erythrocyte sedimentation rate (ESR)

    • Autoimmune diseases: Antinuclear antibody

    • Allergies: Allergy tests

    • Leukemia or other bone marrow disorders: Bone marrow biopsy, immunophenotyping, chromosome analysis

    My report mentions a "left shift." What does this mean?

    A "left shift" is a phrase used to note that there are young/immature white blood cells present. Most commonly, this means that there is an infection or inflammation present and the bone marrow is producing more WBCs and releasing them into the blood before they are fully mature. This is a natural immune response to infection and inflammation.

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