Neutrophils (Absolute)

Having a low neutrophils level is called Neutropenia.

What is Neutropenia?

- Neutropenia is an abnormally low number of neutrophils (a type of white blood cell) in the blood.

- Neutropenia, if severe, significantly increases the risk of life-threatening infection.

- Neutropenia is often a side effect of the treatment of cancer with chemotherapy or radiation therapy.

- Doctors suspect neutropenia in people who have frequent or unusual infections.

- Without the key defense provided by neutrophils, people have problems controlling infections and are at risk of dying from an infection.

- Antibiotics are given if the person has neutropenia and fever or other signs of infection.

How do you test for Neutropenia?

A blood sample is used to make the diagnosis of neutropenia, and a sample of bone marrow may be needed if the cause is not apparent.

What are possible treatment options?

- Treatment depends on the cause and severity of the disorder and can include drugs to stimulate the body's production of neutrophils.

- Neutropenia may resolve quickly when the infection resolves or the exposure stops.

- Chronic neutropenia may last for months or years.

How to classify neutropenia severity:

The typical lower limit of the neutrophil count is about 1500 cells per microliter of blood (1.5 × 109 cells per liter). As the count goes below this level, the risk of infection increases.

Neutropenia severity is classified as:

Mild: 1000 to 1500/mcL (1 to 1.5 × 109/L)
Moderate: 500 to 1000/mcL (0.5 to 1 × 109/L)
Severe: below 500/mcL (0.5 × 109/L)

When the neutrophil count falls below 500 cells per microliter (severe neutropenia), the risk of infection increases greatly. People may even develop infections by the bacteria that normally live harmlessly in the mouth and intestines.

What are the causes of Neutropenia:

Neutropenia has many causes, but they fall into two main categories:

1. Neutrophils are used up or destroyed faster than the bone marrow can produce new ones

Many disorders cause neutrophils to be used up or destroyed. These disorders include certain bacterial infections, some allergic disorders, and some drug treatments (such as drugs used to treat hyperthyroidism). People with an autoimmune disorder can make antibodies that destroy neutrophils and result in neutropenia. People with an enlarged spleen may have a low neutrophil count because the enlarged spleen traps and destroys neutrophils.

2. The production of neutrophils in the bone marrow is reduced

Production of neutrophils in the bone marrow can be reduced by cancer, viral infections such as influenza, bacterial infections such as tuberculosis, myelofibrosis, or deficiencies of vitamin B12 or folate (folic acid). People who have received radiation therapy that involves the bone marrow may also develop neutropenia. Many drugs, including (but not limited to) phenothiazine, sulfa drugs, and many drugs used in cancer treatment (chemotherapy), as well as certain toxins (benzene and insecticides) can also impair the bone marrow’s ability to produce neutrophils. Production of neutrophils in the bone marrow is also affected by a disorder called aplastic anemia (in which the bone marrow may shut down production of all blood cells). Certain rare hereditary disorders also cause a decrease in the number of neutrophils. In cyclic neutropenia, the number of neutrophils rises and falls regularly over a period of weeks. In chronic benign neutropenia, neutrophil counts are low but infections are rare, probably because people produce adequate numbers in response to infection. Severe congenital neutropenia is a group of disorders that prevent neutrophils from becoming mature, and people develop serious infections starting in infancy.

What are Neutropenia symptoms?

Neutropenia itself has no specific symptoms, so it is usually diagnosed when an infection occurs. People may develop fever and painful sores (ulcers) around the mouth and anus. Bacterial pneumonia and other severe infections can occur.

In chronic neutropenia, people may not have many symptoms if the number of neutrophils is not extremely low.

When neutropenia is caused by drugs, people may have a fever, rash, and swollen lymph nodes.

In cyclic neutropenia, people can have symptoms that come and go as their white blood cell count rises and falls over time.

How to treat Neutropenia?

The treatment of neutropenia itself depends on its cause and severity. Drugs that may cause neutropenia are stopped whenever possible, and exposures to suspected toxins are avoided.

The most important thing is to treat any infection that is found. In people with severe neutropenia, infections can rapidly become serious or fatal. Even if doctors cannot diagnose a specific infection, people who have neutropenia and fever are presumed to have an infection. Such people are given antibiotics effective against common infectious organisms.

Sometimes the bone marrow recovers by itself without treatment. The neutropenia accompanying viral infections (such as influenza) may be transient and resolve after the infection has cleared. People who have mild neutropenia generally have no symptoms and may not need treatment.

People who have severe neutropenia can rapidly die as a result of infection because their bodies lack the means to fight invading organisms. When these people develop infections, they are usually hospitalized and immediately given strong antibiotics, even before the cause and exact location of the infection are identified. Fever, the symptom that usually indicates infection in people who have neutropenia, is an important sign that immediate medical attention is needed.

Growth factors called colony-stimulating factors, which stimulate the production of white blood cells by the bone marrow, are sometimes helpful and are given as a injection (under the skin or into a vein).

Corticosteroids may help if the neutropenia is caused by an autoimmune disorder. Antithymocyte globulin or other types of therapy that suppress the activity of the immune system may be given by vein when a disorder such as aplastic anemia is present.

When neutropenia is caused by another disorder (such as tuberculosis or leukemia or other cancers), treatment of the underlying disorder may resolve the neutropenia. Bone marrow (or stem cell) transplantation is not used to treat neutropenia per se, but it may be recommended to treat certain serious causes of neutropenia, such as aplastic anemia or leukemia.

How can you prevent neutropenia?

You cannot prevent the types of neutropenia that are inborn. If you are receiving chemotherapy and your healthcare provider is worried about your low neutrophil levels, they may delay your next round of chemo or reduce your dose. They may also recommend getting injections of G-CSF to boost your white blood cell production, which increases neutrophils.

You can take precautions to prevent infections if you know your neutrophil levels are low:

- Wash your hands frequently with soap and water, or use an alcohol-based hand sanitizer.
- Stay up-to-date on all vaccines, including shots for the flu and COVID-19.
- Avoid people who are sick or crowds where you’re likely to come into contact with a sick person.
- Avoid injuries like scrapes, tears or cuts (including tattoos and piercings), and care for wounds immediately if your skin is damaged.
- Prevent the spread of germs by washing fruits and vegetables, keeping meats away from other foods, preparing meals in a clean kitchen and cooking foods to the proper temperature.
- Don’t share utensils, cups, food or drinks with others.
- Don’t share towels, razors or toothbrushes with others.
- Wear gloves if you’re gardening or working in the yard.
- Avoid picking up pet waste or changing a newborn’s diaper (use gloves and wash your hands afterward if you can’t avoid it).
- Avoid lakes, ponds, rivers and hot tubs.
- Take the prophylactic medications prescribed by your healthcare provider to help prevent infections.

Many of these tips apply to anyone who’s trying to keep from getting sick. If you have neutropenia, you’ll need to take extra care to avoid infection. Ask your provider about additional ways to prevent infection based on your lifestyle and health.

Neutrophilia refers to a higher than normal number of neutrophils on a complete blood count (CBC).

Shift neutrophilia

Shift neutrophilia is usually transient and may occur in association with vigorous exercise or an epinephrine injection and usually lasts 20-30 minutes. Shift neutrophilia is also seen in cases of seizures and paroxysmal tachycardia. No increase in nonsegmented neutrophilic forms occurs, because no change occurs in the inflow of neutrophils from the marrow.

True neutrophilia

True neutrophilia occurs in most cases of neutrophilia that are related to infections. During early infection, the neutrophil count may actually decrease briefly because of margination of cells from the blood. 

Acute infections

Neutrophilia can result from acute infections caused by any of the following pathogens:

- Cocci (eg, staphylococci, pneumococci, streptococci, meningococci, gonococci)

- Bacilli (eg, Escherichia coli, Pseudomonas aeruginosa, Actinomyces species)

- Certain fungi (eg, Coccidioides immitis, Candida albicans)

- Spirochetes

- Viruses (eg, rabies, poliomyelitis, herpes zoster, smallpox, varicella),

- Rickettsia

- Parasites (eg, liver fluke)

Neutrophilia is also seen in the following infectious conditions:

- Furuncles

- Abscesses

- Tonsillitis

- Appendicitis

- Otitis media

- Osteomyelitis

- Cholecystitis

- Salpingitis

- Meningitis

- Diphtheria

- Plague

- Peritonitis

Infections such as typhoid fever, parathyroid fever, mumps, measles, and tuberculosis usually are not associated with leukocytosis.

Neutrophilia can occur in noninfectious conditions such as the following:

- Burns

- Postoperative state

- Acute asthma

- Myocardial infarction

- Acute attacks of gout

- Acute glomerulonephritis

- Rheumatic fever

- Collagen-vascular diseases

- Hypersensitivity reactions

- Cigarette smoking

Neutrophilia in severe burns is accompanied by a shift to the left in the differential and the presence of degenerative forms on the peripheral smear, including toxic granulation and Dohle bodies.

Postoperatively, neutrophilia occurs for 12-36 hours as a result of tissue injury–related increases in adrenocortical hormones. Leukocytosis can also occur in intestinal obstruction and strangulated hernia.

Neutrophil activation during cardiopulmonary bypass (CPB) surgery may occur because of the release of complement chemotactic products or the local release of interleukin (IL)-8. The expression of beta-2 integrins on the surface of neutrophils is increased in response to IL-8 and to certain components of complement during CPB. Both IL-8 and the complement system are activated during CPB.

Patients with acute myocardial infarction experience a transient but significant rise in serum IL-8 concentration within 24 hours after the onset of symptoms. An upregulation of messenger RNA (mRNA) for IL-8 occurs in the inflammatory infiltrate near the border between necrotic and viable myocardium. Thus, IL-8 is likely involved in the pathogenesis of myocardial injury following coronary artery bypass graft (CABG) surgery.

Metabolic and toxic causes:

Neutrophilia commonly occurs in the following:

- Diabetic ketoacidosis

- Preeclampsia

- Uremia, especially with uremic pericarditis

Neutrophilia can result from poisoning with lead, mercury, digitalis, camphor, antipyrine, phenacetin, quinidine, pyrogallol, turpentine, arsphenamine, and insect venoms. In patients with lead colic, leukocyte counts as high as 20 × 109/L may be seen.

Hematologic causes:

Acute hemorrhage, especially into body spaces such as the peritoneal cavity, pleural cavity, joint cavity, and intracranial cavity (eg, extradural, subdural, or subarachnoid space) is associated with leukocytosis and neutrophilia. This is probably related to the release of adrenal corticosteroids and/or epinephrine secondary to pain. Local inflammation due to pressure necrosis and the generation of chemotactic factors from the lysis of leukocytes also contributes.

During the first 1-3 hours of an acute hemorrhage, neutrophilia occurs because of a shift from the marginal pool to the circulating pool. After 3-6 hours, neutrophils are released from the marrow. Acute hemolysis leukocytosis occurs following a transfusion of mismatched blood or during acute hemolytic disease.

Neutrophilia can occur with the following:

- Anemia (eg, in chronic infections)

- Polycythemia (polycythemia vera)

- Increased platelet count (essential thrombocythemia)

- Decreased platelet count (sepsis)

- Nucleated red blood cellsRBCs (myelofibrosis, malignancies)

- Neoplasms and blood malignancies

Chronic myelocytic leukemia (CML), polycythemia vera, myelofibrosis, and myeloid metaplasia result in neutrophilia.

Neutrophilia can also occur in association with rapidly growing neoplasms when the tumor outgrows its blood supply. This process is thought to be due to tumor necrosis factor (TNF)-alpha. Some tumor types produce neutrophilic growth factors (eg, granulocyte colony-stimulating factor [G-CSF] production by squamous cell cancers of the head and neck).

Physiologic neutrophilia:

Strenuous exercise and epinephrine injection can cause transient neutrophilia. Physiologic neutrophilia is also seen in pregnancy, labor, and in newborns.

Genetic causes:

Hereditary neutrophilia has been described in one family with an activating germline mutation in colony-stimulating factor 3 receptor (CSF3R).  

Chronic neutrophilic leukemia (CNL) is a rare myeloproliferative disorder also associated with mutations in CSF3R that may activate this receptor, leading to the proliferation of neutrophils that are the hallmark of this leukemia. CSF3R is found in about 80% of cases. Also common are mutations in SETBP1 (14%–50%) and various spliceosome proteins.

Other causes:

Neutrophilia can occur in association with convulsions and paroxysmal tachycardia. Short- or long-term administration of corticosteroids causes neutrophilia. Neutrophilia is seen in association with Cushing disease.

Neutrophilia may be present without an identifiable cause, in which case it is known as chronic idiopathic neutrophilia. Persistent neutrophilia (PN) has been defined as an absolute neutrophil count of ≥7.8 × 109/L) on at least three CBCs at least 2 months apart without an identifiable etiology.