Neutrophils are a type of white blood cell (WBC or granulocyte) that protect us from infections, among other functions. They make up approximately 40 percent to 60 percent of the white blood cells in our bodies, and are the first cells to arrive on the scene when we experience a bacterial infection. A normal (absolute) neutrophil count is between 2500 and 7500 neutrophils per microliter of blood. The neutrophil count may be high with infections, due to increased production in the bone marrow as with leukemia, or due to physical or emotional stress. A low number of neutrophils may also be a sign of disease in conditions such as leukemia, some infections, vitamin B12 deficiency, chemotherapy, and more.
Neutrophils make up the largest fraction of blood cells produced by the bone marrow. They are our “first responders” playing the role of the first line of defense against infectious organisms that enter our bodies.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, living on average only 8 hours, but our bodies produce 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.
Anatomy and Structure
Neutrophils can be seen clearly under the microscope as cells with a characteristic 2 to 5 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)? 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 2 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, or a basophil.Neutrophils begin as myeloblasts, which mature into promyelocytes, myelocytes, metamyelocytes, bands, and then mature neutrophils.
A neutrophil count is check as part of a complete blood count (CBC). A normal ANC or absolute neutrophil count is usually between 2500 and 7500 neutrophils per microliter.Levels of neutrophils less than 2500 are referred to as neutropenia, though the degree of decrease is important. An ANC 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.
Conditions With an Abnormal Number of Neutrophils
When doctors check a complete blood count (CBC) or white blood cell count (WBC) the most common abnormality is 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.
Causes of Neutrophilia
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. Stress hormones in our body cause a greater than a normal number of these cells to be released from the bone marrow.
- Proliferative (increased production in the bone marrow): 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.
- 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.
Conditions Which May Cause Neutrophilia
Some specific causes of an increased neutrophil count (neutrophilia) include:
- Blood cell-related cancers such as leukemia
- Autoimmune disorders such as rheumatoid arthritis
- Trauma and burns
Immature Neutrophils (Bands) in the Blood
Most of the neutrophils in our 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 doctor 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.
Causes of Neutropenia
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.Mechanisms that can result in a low neutrophil count may include
- Decreased or absent bone marrow production: 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.
- Demand for more neutrophils – For example, to fight 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 immune destruction due to antibodies directed against self in conditions such as lupus.
- Destruction of neutrophils already produced.
- Cyclic neutropenia.
Via the mechanisms above, a decreased neutrophil count could be due to:
- Aplastic anemia
- Radiation exposure
- Blood-related cancers which infiltrate the bone marrow such as leukemia
- Viral infections
- Overwhelming infections (sepsis)
- Rickettsial infections
- Typhoid fever
- Drug reactions: For example, to penicillin, ibuprofen, and phenytoin
- 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)
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, our bodies are less able to fight off infections, even with bacteria that ordinarily do not cause serious infections.
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, and can 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 examination: 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
Examples: Olivia’s neutrophil count was low following her chemotherapy treatment, so her oncologist recommended she begin antibiotics to prevent an infection.