The ANC calculator (Absolute Neutrophil Count calculator) is a tool that enables to estimate the total count of neutrophils which is useful in the assessment of the risk connected with infectious conditions such as sepsis in patients undergoing chemotherapy. It allows for quick diagnosis of neutropenia - a condition when the number of neutrophils in blood is substantially lowered.

In this article, we will describe what are neutrophils and what happens when their concentration in the blood significantly drops - neutropenia. Do you wonder what may be its causes? We have also answered this question and explained how neutropenia is treated!

The necessary indicator in evaluation of neutropenia, is Absolute Neutrophil Count (ANC). In this article you will learn more about ANC and how to interpret its result. You will also find out what the ANC formula is.

If you are interested in medicine and treatment, check out our dosage calculator which estimates the dose of any medication basing on your weight or GFR calculator that finds your glomerular filtration rate and helps you diagnose kidney malfunction!

What are neutrophils?

Neutrophils are the most numerous subpopulation of granulocytes and white blood cells. They are produced from the stem cells in the bone marrow together with other granulocytes such as eosinophils , basophils and agranulocytes - lymphocytes and monocytes. Every human produces approximately 1011 neutrophils daily [sic!] which live only for a few days.

Part of the neutrophils leaving bone marrow are so-called band neutrophils or band cells. These are cells which are though still immature, but just one step before becoming fully matured segmented neutrophils. An increased level of band neutrophils, so-called bandemia or left shift are the markers of increased production of white blood cells and releasing more white blood cells from bone marrow to bloodstream. This happens most often due to infection or inflammation of another kind.

Neutrophils are an essential part of the immune system, specifically innate immune system. Their primary task is to participate in phagocytosis. They are recruited to the site of injury within minutes following the beginning of the acute inflammatory process resulting, e.g. from the bacterial infection. Neutrophils migrate then from blood vessels to the interstitial tissue, where they phagocyte (kill and eat) bacteria. Together with bacteria, neutrophils are the main component of pus.

What is neutropenia? - signs and symptoms

Neutropenia is defined as a low neutrophil count. Generally accepted reference range for neutrophils is 1500 to 8000 cells per microliter (µl) of blood. However, most healthy people have more than 2000 neutrophils per microliter of blood. The lower the neutrophils, the more severe the neutropenia and the more probable and dangerous are complications.

There are three major mechanisms which are involved in the development of neutropenia:

  1. Reduced production or ineffective granulopoiesis (production of granulocytes which takes place in bone marrow)
  2. Increased destruction or utilization of neutrophils
  3. A shift from the circulating (blood vessels) to the marginal pool (e.g. spleen in hypersplenism)

When may you suspect neutropenia?

The most important sign is vulnerability to infections, especially severe or recurrent bacterial infections of the skin, perirectal area or mouth. Also recurrent pneumonia is typical in patients with neutropenia. People with low absolute neutrophils often suffer from ulcers, abscesses, swollen gums and mouth sores. They also very often present with feverishness or low-grade fever, but also hypothermia is relatively common for those people.

Keep on reading to learn more about cancer-induced neutropenia and other causes of neutropenia!

What are the causes of neutropenia?

Yemenite Jews and other populations, including Ethiopian Jews and Bedouins, have low neutrophil counts, and this condition is called benign ethnic neutropenia because it is not associated with an increased risk of infection. Elsewhere neutropenia can be a hereditary disease (so-called severe congenital neutropenia) or may develop during the life as a symptom of a disease or a side effect of a treatment.

Diseases which may cause neutropenia include:

  • infectious diseases, especially viral infections (HIV, Epstein-Barr Virus, Cytomegalovirus) and tuberculosis, malaria, dengue fever,
  • vitamin deficiency (especially vitamin B12 or folic acid),
  • hematologic conditions (leukemias, aplastic anemia, myelodysplastic syndrome, myelofibrosis),
  • congenital disorders and syndromes (severe congenital neutropenia, Kostman syndrome, Fanconi anemia, Diamond–Blackfan anemia),
  • autoimmune diseases (rheumatoid arthritis - Felty's syndrome, systemic lupus erythematosus, autoimmune neutropenia, Crohn's disease),
  • hypersplenism (increased destruction of blood cells by the spleen because of its hyperfunction).

Absolute neutrophils may also be lowered as a result of treatment due to other conditions. This treatment methods and drugs include:

  • cancer chemotherapy,
  • radiation therapy,
  • antibiotics, e.g. trimethoprim/sulfamethoxazole,
  • anticonvulsants, e.g. valproate,
  • antipsychotic, e.g. clozapine,
  • antithyroid, e.g. propylthiouracil,
  • post vaccination neutropenia.

Regardless of the primary reason, you should always remember that neutropenia can be life-threatening due to its complications and thus in case of suspecting it you should consult your doctor!

Cały nagłówek do wymiany!

What is the Absolute Neutrophil Count?

Absolute Neutrophil Count calculates total number of neutrophils, both mature and immature in one microliter of blood. Measurement of ANC is vital in many clinical situations.

First of all, it is mandatory in diagnosing and classifying neutropenia. You cannot diagnose neutropenia without counting ANC! ANC is also a measure of risk of infection, including severe and life-threatening infections like sepsis.

Additionally, the diagnosis of neutropenia imposes an obligation on the doctor to actively seek possible severe complications, try to prevent and treat them. Moreover, patients with such conditions should not receive certain drugs, some other should be absolutely discontinued. That is why using ANC formula and calculating absolute neutrophils is crucial.

ANC formula

The only data that is necessary for calculating ANC are the results of blood tests (routine and differential). You will need the following numbers:

  • the total number of white blood cells (WBC), measured in cells/μL;
  • percentage of mature neutrophils (called segs or segmented cells);
  • percentage of immature neutrophils (called bands).

Simply input all of these numbers into the ANC formula to calculate the Absolute Neutrophil Count.

ANC = WBC * (segs[%] + bands[%]) / 100

The result, ANC, will also be measured in cells/μL.

Check out our other calculators that rely on the the complete blood count (CBC) results: Absolute Reticulocyte Count and Corrected Reticulocyte Count!

How to calculate ANC? - interpreting the result

  1. Do a complete blood count (CBC). Remember that the results should be as recent as possible.
  2. Note down the number of white blood cells (WBC) per microliter. Let's assume it is equal to 6000 cells/μL.
  3. Write down the percentage of mature (segs) and immature (bands) neutrophils in your blood sample. Let's assume the percentage is equal to 30% for segs and 3% for bands.
  4. Insert all of the numbers into the ANC formula:

ANC = WBC * (segs[%] + bands[%]) / 100

ANC = 6000 * (30 + 3) / 100

ANC = 6000 * 0.33

ANC = 1980 cells/μL

  1. Take a look at the five following interpretation rules!

The ANC results are divided into risk categories as follows:

  • Category 0: ANC higher than 2000 cells/μL. This is the reference range - in typical adults, ANC ranges from 2000 to 8000 cells/μL.
  • Category 1: ANC between 1500 and 2000 cells/μL.
  • Category 2: ANC between 1000 and 1500 cells/μL. This is the condition of mild neutropenia.
  • Category 3: ANC between 500 and 1000 cells/μL. This is the condition of moderate neutropenia.
  • Category 4: ANC below 500 cells/μL. This is the condition of severe neutropenia.

You should always remember that the value of ANC changes dynamically and reflects the patient's response to chemotherapy treatment or marrow transfer. It is often measured daily to assess whether the patient should receive additional antibiotics or bacteria cultures.

How to treat neutropenia?

Neutropenia management depends on its severity and the primary cause. Treatment is usually mandatory in cases of severe neutropenia. The management of choice in drug-induced neutropenia is discontinuation of the drug admission or, in cases of chemotherapy-induced neutropenia, lowering the dose of the drugs. In other cases, treatment called granulocyte colony-stimulating factor (G-CSF) is used. This is the agent stimulating the production of all kind of white blood cells, including neutrophils, in a bone marrow. This method is used in many different kinds of neutropenia, including neutropenia after chemotherapy and radiation therapy. In some cases of severe neutropenia caused by bone marrow aplasia, stem cells transplantation is used.

Equally significant as the use of drugs are measures aimed at the prevention of infections. These include:

  • hygiene,
  • good dental care,
  • avoiding contact with sick people,
  • avoiding animal waste and not changing infants' diapers,
  • avoiding undercooked meat, raw fruits, vegetables.

You should always remember that the primary objective in the management of patients with neutropenia should be to prevent possibly life-threatening complications.

Neutropenia complications

The common consequences of neutropenia are infections, including severe infections of the central nervous system, sepsis and recurrent skin infections. 70% of untreated patients with severe neutropenia die during first 24-hours! This is mainly caused by two most important neutropenic complications: febrile neutropenia and neutropenic enterocolitis.

Continue reading to get to know more about febrile neutropenia and neutropenic enterocolitis!

Febrile neutropenia

Severe neutropenia accompanied by a fever of recent onset is a medical emergency requiring immediate investigation and treatment. Febrile neutropenia is generally defined as a rise in axillary temperature to above 38.5 °C for more than one hour while having an absolute neutrophil count of fewer than 500 cells/μL. Other definitions are also used like 38 °C during one to four hours with severe neutropenia. Every second patient with such a condition already has an infection and 40% of them have a detectable bacteremia (presence of bacteria in the blood) what may lead to the development of neutropenic sepsis.

It is one of the most common life-threatening oncological emergency, as it usually appears during chemotherapy.

Since the early eighties of the previous century it was recognized that, among other explanations, early treatment with broad spectrum antibiotics of neutropenic fever patients greatly reduced the mortality rate. Nowadays, to the treatment of febrile neutropenia antifungal agents are often added. Administration of these drugs is usually discontinued when ANC > 500 cells/μL and fever abates.

Neutropenic enterocolitis / typhlitis

Neutropenic enterocolitis (also called typhlitis or cecitisis) is an inflammation of cecum (a part of large intestine) associated with infection in a patient with low absolute neutrophils. Typhlitis should be suspected in a patient with neutropenia who reports diarrhea, bloating, abdominal tenderness, nausea or vomiting. It is usually diagnosed with computed tomography. The treatment is based on antibacterial treatment and surgical treatment in cases of intestinal perforation.

ANC as a biomarker

Recently, there have been published in the medical journals results of many studies suggesting that ANC may be an independent prognostic factor for the success or failure of the therapy of different diseases. It has been proved, for example, in patients with:

Łukasz Białek, MD and Bogna Haponiuk

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