What Is Neutropenia?

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Neutropenia is a condition in which the level of neutrophils circulating in the blood is lower than normal. Neutrophils are a type of white blood cell with an important role in fighting infection.

Neutrophils begin as stem cells in the bone marrow. During a process called hematopoiesis, bone marrow stem cells differentiate into the various types of blood cells and are eventually released into the blood. Neutrophils circulate in the blood, where they release antibacterial chemicals and ingest bacteria.

This article discusses the types, symptoms, causes, and treatment of neutropenia.

Doctor viewing a blood smear under a microscope

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Neutropenia Levels

Most neutrophils are in the bone marrow, with only about 2% circulating in the blood at any given time. A blood test reports the number of neutrophils in the blood, or the absolute neutrophil count (ANC), as number of neutrophils per microliter (uL) of blood.

  • Mild neutropenia: 1,000–1,500 / uL
  • Moderate neutropenia: 500–1,000 / uL
  • Severe neutropenia: Less than 500 /uL

Types of Neutropenia

Neutropenia can be classified by whether it is acute (sudden) or chronic (long term), and whether it is inherited or acquired later in life.

Inherited Neutropenias

Many genetic mutations causing neutropenia have been identified. Some of the genetic neutropenia syndromes include:

Acquired Neutropenias

Neutropenia can also be acquired. These types include:

  • Infection-related neutropenia
  • Medication-related neutropenia
  • Nutritional deficiency–related neutropenia
  • Malignancy-related neutropenia
  • Chronic idiopathic neutropenia
  • Autoimmune neutropenia
  • Felty syndrome

Symptoms

Neutropenia may not cause any symptoms at all, or it can result in recurring or severe infections.

Generally, the lower the ANC, the higher the risk of infection, with ANC levels in the severe range having the highest risk. Disorders affecting bone marrow production of neutrophils further increase infection risk.

Signs of infection can include:

  • Fever or chills
  • Fatigue
  • Body aches
  • Mouth sores
  • Sore throat
  • Sinus and ear pain
  • Cough and shortness of breath
  • Skin redness and swelling
  • Painful or frequent urination
  • Diarrhea
  • Pain in the rectal area

Causes

Causes of neutropenia can be broadly categorized as decreased neutrophil production, altered storage of neutrophils, and increased neutrophil destruction. Within these categories are multiple specific causes of neutropenia.

Decreased Neutrophil Production

Neutrophils begin as stem cells in the bone marrow that differentiate into cells called granulocytes. Granulocytes are so named because granules are visible when viewed under a microscope. In the bone marrow, these cells undergo several steps of maturation and are released into the blood as neutrophils.

Decreased neutrophil production in the bone marrow can be caused by:

  • Nutritional deficiency: Production of blood cells requires vitamin B12, folate, and copper. Severe deficiency of these vitamins results in neutropenia, as well as low levels of other cells such as red blood cells (anemia). Vitamin deficiency can be caused by low dietary intake of nutrients or from poor absorption, such as after bypass surgery.
  • Bone marrow infiltration: Cancer cells, such as in leukemia and multiple myeloma, can disrupt neutrophil production. Typically, other cell lines like red blood cells and platelets are also affected.
  • Congenital: Inherited mutations including Fanconi's anemia, dyskeratosis congenita, and Shwachman-Diamond syndrome can result in decreased neutrophil and other white blood cell production.
  • Chemotherapy: Chemo suppresses bone marrow production of all blood cells. A common side effect is pancytopenia, a decrease in all blood cell lines, including neutrophils.
  • Radiation: Radiation has the greatest effect on cells that are rapidly dividing. Because the bone marrow is constantly making new blood cells, it is sensitive to the effects of radiation.
  • Infection: Viral hepatitis, parvovirus, and human immunodeficiency virus (HIV) can affect bone marrow production of neutrophils.

Neutrophil Storage

Neutrophils exist in several places in the body. The vast majority are in the bone marrow. The rest are either in tissues, are circulating in the blood, are attached to blood vessel walls (called margination), or are isolated in the liver or spleen.

Neutrophils attached to blood vessel walls can be released into circulation and travel to wherever they are needed. Some conditions can cause neutrophils to stick more to the blood vessel walls or to collect in the spleen, resulting in neutropenia.

  • Infection: In sepsis, a severe response to an infection that results in dysfunction of organ systems, too many neutrophils can be attached to blood vessel walls, resulting in low-circulating neutrophils.
  • Splenomegaly, or an enlarged spleen: Can be caused by many conditions. Regardless of the cause, an enlarged spleen can isolate neutrophils, along with other white blood cells, red blood cells, and platelets. Treatment may require removing the spleen surgically.

Increased Neutrophil Destruction

Certain disorders or factors can result in increased neutrophil destruction, including:

  • Primary autoimmune neutropenia is a pediatric disorder in which antibodies directed against neutrophils result in their destruction.
  • Secondary autoimmune neutropenia is associated with other autoimmune disorders like rheumatoid arthritis, Crohn's disease, and lupus.
  • Congenital: Mutation of some genes involved in apoptosis (cell death) can result in premature neutrophil destruction.
  • Viral infection: Infection with viruses like Epstein-Barr virus, and possibly COVID-19, can result in antibodies that destroy neutrophils.
  • Medications can cause neutrophil destruction through production of antibodies, enhancing apoptosis, or the complement pathway. Examples include some antibiotics like penicillin and cephalosporins, and medications used to treat hyperthyroidism (overactive thyroid).

Diagnosis

Neutropenia is diagnosed from a blood test called complete blood count (CBC) with differential. Importantly, the CBC with differential will also reveal if other cell lines are low.

Pancytopenia is diagnosed when white blood cell, red blood cell, and platelet counts are low. Presence of isolated neutropenia vs. pancytopenia is helpful in diagnosing the cause of neutropenia.

Another diagnostic option is a blood smear, a test in which a blood sample is examined under a microscope. Size, shape, and characteristics of the neutrophil can give important clues to the cause. For example, having large neutrophils with many lobes in their nuclei suggests vitamin deficiency. Finding immature cells without any mature neutrophils is concerning for leukemia (cancers of the blood).

Other blood tests can be useful for diagnosing the cause of neutropenia. Tests for HIV, Epstein-Barr virus, and viral hepatitis can rule out these infections. Inflammatory markers and antibody tests can suggest an autoimmune condition.

Sometimes a bone marrow biopsy, in which a small sample of bone marrow is removed from your bones for testing, is necessary to evaluate for bone marrow malignancy or infiltrative disorders.

Treatment

Treatment of neutropenia depends on the underlying cause and includes treating underlying infections, supplementing nutritional deficiencies, and adjusting or discontinuing offending medications.

Medication called granulocyte colony stimulating factor (G-CSF) can be given to stimulate the bone marrow to produce more neutrophils. Neupogen (filgastrim) and Neulasta (pegfilgastrim) are commonly used for treatment of neutropenia, especially when caused by chemotherapy.

Antibiotics may be recommended as a precaution against infection in some cases when neutropenia is very severe and infection risk is high.

Precautions to avoid infection include:

  • Handwashing
  • Dental care
  • Keeping vaccines current (check with healthcare provider when receiving vaccines, as some live vaccines are not appropriate for people with a compromised immune system)
  • Use care when preparing foods by washing fruits and vegetables, keeping raw meat and poultry separate from other food, and cooking foods all the way
  • Avoid exposure to mulch and animal droppings

Summary

Neutropenia refers to abnormally low levels of neutrophils in the blood that can increase the risk of infection. Although it is a common side effect of some cancer treatments, neutropenia is a broad diagnosis that can have many other causes.

A Word From Verywell

Finding out your neutrophil counts are low can be a stressful experience, particularly if the cause is not clear. It can be discouraging when chemotherapy is the cause. Although you do not have much control over the number of neutrophils in your blood, you can take steps to avoid infection. Close follow-up with a healthcare provider and blood count monitoring are essential to your care.

Frequently Asked Questions

  • What is the most common cause of neutropenia?

    The most common cause of acquired neutropenia is medication. Myelosuppressive drugs, including chemotherapy, have the known and predictable effect of suppressing blood cell production in the bone marrow. Other medications, on the other hand, have neutropenia as an unintended and rare side effect. Nonsteroidal anti-inflammatory drugs (NSAIDs), antibiotics like penicillin, seizure medications, and medications that treat hyperthyroidism can all cause neutropenia.

  • What are the levels of neutropenia?

    The severity of neutropenia is based on the following values for absolute neutrophil count (ANC), as measured by neutrophils per microliter of blood:

    • Mild: 1,000–1,500
    • Moderate: 500–1,000
    • Severe: Less than 500
  • What deficiencies cause neutropenia?

    Deficiencies in vitamin B12, folate, and copper can cause neutropenia. These nutrients are important in the production of neutrophils and other blood cells. Deficiencies are often accompanied by a low red blood cell count (anemia). The good news is that neutropenia caused by nutritional deficiency can be corrected with appropriate supplementation. Always discuss supplements with your healthcare provider, as it's possible to take too much of a vitamin or mineral, resulting in toxicity.

  • Can neutrophils go away?

    As part of their normal life cycle, neutrophils undergo programmed cellular death and are ingested by cells called macrophages. When bone marrow production is severely suppressed, such as when receiving chemotherapy for bone marrow transplant, absolute neutrophil count—the number of neutrophils circulating in the blood—can go to zero. The risk of infection is very high when neutrophil counts approach zero.

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