What does high white blood cells and high neutrophils mean

Neutrophils are a type of white blood cell (WBC or granulocyte) that, among other things, protect you from infection. They make up approximately 40% to 60% of the white blood cells in your body.

A normal (absolute) neutrophil count is between 2500 and 6000 neutrophils per microliter of blood. A high neutrophil count may be due to infections, a leukemia cancer, or physical or emotional stress. Low neutrophil levels, or neutropenia, also may be a sign of leukemia, some types of infection, vitamin B12 deficiency, chemotherapy, and more.

This article discusses neutrophils and their role in maintaining your health. It explains neutrophil blood tests and counts, as well as the causes of neutrophil level changes and how they are diagnosed.

Function and Structure

Neutrophils make up the largest fraction of blood cells produced by the bone marrow. They play the role of the first line of defense against infectious organisms that enter your body.

These cells are the first cells to arrive on the scene when we experience bacterial infections. Damage to cells results in the release of "chemokines" which attract neutrophils to the site in a process called chemotaxis. Neutrophils may be better known to the casual observer as the primary component of pus.

Neutrophils address foreign invaders by "eating them," a process referred to as phagocytosis, or by taking them up into the cell in a process called endocytosis. Once the foreign organism is inside the neutrophil, it is "treated" with enzymes which result in the destruction of the organism. Neutrophils also help regulate the immune response in general.

Neutrophils have a very short lifespan of less than 24 hours, but your body produces roughly 100 billion of these cells each day. After being released from the bone marrow, around half of these cells are present along the lining of blood vessels and the other half are found in tissues of the body.

Neutrophils can be seen clearly under the microscope as cells with a characteristic two to five lobes in the nucleus, and which stain pink or purple with neutral dyes. The term "PMN" or polymorphonuclear leukocyte refers to this finding.

Neutrophils, White Blood Cells, and the Immune System

It can be confusing if you hear about white blood cells and neutrophils. If neutrophils are only one type of white blood cell, why do oncologists talk interchangeably about a low white blood cell count and a low neutrophil count with chemotherapy (chemotherapy-induced neutropenia) when treating cancer?

A simple answer is that a low level of neutrophils, in particular, may be most dangerous in predisposing people to infections. 

All of the blood cells (white blood cells, red blood cells, and platelets) are formed in the bone marrow — the spongy tissue in the center area of bones such as the hip. In the bone marrow, all of these cells originate as one type of cell known as a hematopoeitic stem cell.

These stem cells then undergo differentiation into the different types of cell in a process known as hematopoiesis. Since all of these cells begin with a common stem cell, processes which damage the bone marrow—such as chemotherapy—often affect all of the different types of blood cells. This is referred to as bone marrow suppression from chemotherapy.

In addition to red blood cells and platelets, there are several types of white blood cells. White blood cells develop along two different lines. 

A stem cell can develop either along the lymphoid line, which results in the eventual formation of T and B lymphocytes, or the myeloid line. A cell in the myeloid line can develop into:

• A neutrophil
• An eosinophil
• A monocyte
• A basophil

Neutrophils begin as myeloblasts, which mature in stages known as:

• Promyelocytes
• Myelocytes
• Metamyelocytes
• Bands
• Mature neutrophils

Normal Neutrophil Blood Test Percentage

Certain blood tests will give you and your healthcare provider the percentage of each type of WBCs. The normal range for neutrophils on a blood differential test is 40% to 60%. Lymphocytes account for 20% to 40%, with monocytes, eosinophils, basophils, and bands making up the rest.

Neutrophil Count

A neutrophil blood test is part of a complete blood count (CBC). Levels of neutrophils less than 2500 are referred to as neutropenia, though the degree of decrease is important. A level of less than 1000 is most serious, and can seriously predispose someone to infections.

Your blood count report may break down neutrophils into two categories: segmented or mature neutrophils, and immature neutrophils known as bands. In serious infections, the bone marrow is stimulated to release more neutrophils (immature neutrophils) resulting in an elevated number of bands on your report.

When healthcare providers check a complete blood count (CBC) or white blood cell count (WBC) they also look for an increase or decrease in the expected number of neutrophils. Testing for neutrophils is, therefore, a very important part of the laboratory evaluation of disease.

Appearance of Neutrophils

The appearance of neutrophils, or "morphology" can also be helpful in diagnosing disease. While a complete blood count determines the number of white blood cells, a peripheral blood smear for morphology is often done to see specific characteristics that may be present in neutrophils.

For example, toxic granulations may be seen within the neutrophils with serious infections, hypersegmented (more than 5 lobes) neutrophils may be seen with vitamin B12 deficiency and folate deficiency, and more.

Neutrophilia: When Neutrophils Are Too High

Thinking about the function of neutrophils makes understanding an increase in the number easier to understand. Mechanisms that can increase the number of these white blood cells include:

Reactive

With reactive neutrophilia, there is an increase in the number of neutrophils in response to infections or stress. Anxiety can cause neutrophilia, as stress hormones in your body cause a greater than normal number of these cells to be released from the bone marrow. 

Proliferative

Proliferative neutrophilia refers to an increase in the number of neutrophils due to an increase in their production in the bone marrow.

This is most commonly seen with cancers, such as acute myelocytic leukemia. The type of white blood cells in this case are often abnormal, and even though there are more neutrophils present, they do not function as well as "normal" neutrophils.

Demargination

Neutrophils often "live" attached to the lining of blood vessels. These neutrophils may become "demarginated" and circulate in the bloodstream due to stress, infections, and sometimes exercise.

The release of neutrophils along the blood vessels into the bloodstream is one reason why the white blood cell count can sometimes rise rapidly. It takes longer for new neutrophils to be produced or released from the bone marrow.

Conditions That May Cause Neutrophilia

Some specific causes of an increased neutrophil count (neutrophilia) include:

• Infections
• Stress 
• Blood cell-related cancers such as leukemia
• Autoimmune disorders such as rheumatoid arthritis
• Trauma and burns
• Smoking
• Pregnancy
• Thyroiditis
• Eclampsia

Immature Neutrophils (Bands) in the Blood

Most of the neutrophils in your blood are mature neutrophils. Immature neutrophils may be found on a blood smear if the body is stressed and there is a great need for more neutrophils.

When this occurs, an increased number of immature neutrophils can make their way to the blood from the bone marrow before reaching maturity. Your healthcare provider may mention that you have an increased number of bands—or even less mature neutrophils—on your blood count.

Alternately, an increased production of immature neutrophils may occur with conditions such as myelodysplastic syndromes and leukemias such as acute promyelocytic leukemia.

Neutropenia: When Neutrophils Are Too Low

Your neutrophil count may be decreased alone, or instead, be reduced along with other types of blood cells. The term pancytopenia refers to a reduction of all three of the major types of blood cells; red blood cells (referred to as anemia) platelets (referred to as thrombocytopenia) and white blood cells.

Several mechanisms can result in a low neutrophil count.

Decreased or Absent Bone Marrow Production

The bone marrow may slow down or cease to produce white blood cells, for example, when the bone marrow is injured as with chemotherapy, or a vitamin deficiency is present which causes inadequate production.

Bone Marrow Infiltration

When the bone marrow is "taken over" by cells such as cancer cells it is referred to as bone marrow infiltration. The bone marrow may also be taken over by scar tissue (fibrosis) in conditions such as myelofibrosis.

Demand for More Neutrophils

More neutrophils may be needed in specific situations, such as to fight an infection or in response to trauma. Initially, with most bacterial infections, the neutrophil count is increased. With serious infections, however, a low neutrophil count may result as the immune system is overwhelmed by the infection.

Decreased Survival of Neutrophils

While infections usually produce an increased neutrophil count, overwhelming infection, as well as infections with some viruses and rickettsial infections can result in decreased survival of neutrophils and a low count. Neutrophils may also face destruction due to antibodies produced in autoimmune conditions such as lupus that attack the body itself.

Destruction of Neutrophils Already Produced

Neutrophils that have been released from the bone marrow and are circulating in the body may be destroyed in a few different ways. This may occur with autoimmune conditions in which antibodies (autoantibodies) are produced that directly destroy the neutrophils.

Cyclic Neutropenia

This rare condition known as cyclic neutropenia can be genetic or acquired, and is marked by intermittent periods of a low white count fluctuating with a normal WBC count.

Importance of a Low Neutrophil Count

The seriousness of a low neutrophil count depends on several factors, especially the degree of neutropenia. You are probably familiar with stories of "bubble babies"—children who are born with a severely compromised immune system, but there are many degrees in between. 

A low neutrophil count is one of the serious side effects of chemotherapy. When these cells are limited in either number or function or both, your body is less able to fight off infections, even with bacteria that ordinarily do not cause serious infections.

Conditions That May Cause Neutropenia

Via the mechanisms above, a decreased neutrophil count could be due to:

• Chemotherapy
• Aplastic anemia
• Radiation exposure
• Myelodysplasia
• Blood-related cancers which infiltrate the bone marrow such as leukemia
• Viral infections
• Overwhelming infections (sepsis)
• Rickettsial infections, such as Rocky Mountain spotted fever
• Typhoid fever
• Hypersplenism, or an overactive spleen
• Drug reactions, such as to penicillin, ibuprofen, and phenytoin
• High blood sugar
• Vitamin B12 deficiency (megaloblastic anemia) and folic acid deficiency
• Kostmann's neutropenia (a genetic condition which affects young children)
• Idiosyncratic, meaning nobody knows for certain why a neutrophil count is low

Diagnosis

If the neutrophil count is abnormal on a CBC, further evaluation is needed. This usually begins with a history and physical exam keeping in mind the potential causes of abnormal levels.

A peripheral smear (differential) is often the next step. It can be used to look for any other visible abnormalities in the blood cells, including the neutrophils (such as the presence of immature neutrophils not ordinarily found in the blood called blasts). A CBC may also be repeated to rule out lab error.

Further testing will depend on the possible causes of an abnormality and may include:

• A bone marrow biopsy to evaluate the cells at their origin in the bone marrow
• Tests to evaluate for infections
• Blood tests, such as thyroid function tests, vitamin B12 level, and more

Summary

Neutrophils are a type of white blood cell (WBC) that play a key role in fighting off infection. Your level of neutrophils in the blood can change, depending on a number of factors including infection, stress, chemotherapy treatment, or nutritional deficiencies.

In some cases, your neutrophil levels will be high. This condition is called neutrophilia. In cases of neutropenia, the level may be low—even dangerously low. Your healthcare provider can begin with blood tests and move forward in diagnosing the cause of any neutrophil level changes.

Frequently Asked Questions

• Does COVID-19 cause high neutrophils?

  Yes. COVID-19 does cause the immune system to produce additional white blood cells. Doctors think that people who produce an excessive amount of neutrophils may be at risk for more severe symptoms of COVID.

• Does neutropenia cause fatigue?

  Yes, a low neutrophil level is associated with fatigue. This can place you at greater risk of infection.

• What does absolute neutrophil mean on a blood test?

  Absolute neutrophil count tells the doctor the number of neutrophils in your blood. A count below 2500 may mean your immune system isn't working properly and you’re at risk for infection. A count above 6000 may be a sign of infection, inflammation, leukemia, or intense physical or emotional stress.

What causes neutrophils and WBC to be high?

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