Neutropenia (Low Neutrophil Count)

What neutrophils do and what the numbers mean

Neutrophils make up about half to two-thirds of white blood cells. They are made in the bone marrow and live only a day or so in the blood, so the marrow produces billions every day. When bacteria enter the body, neutrophils rush to the site, engulf and kill them. Pus is largely dead neutrophils.

Your absolute neutrophil count (ANC) is calculated from a complete blood count (CBC) with differential: total white cells multiplied by the percentage of neutrophils.

How long the count stays low matters as much as the number. A few days of severe neutropenia is less risky than weeks.

Symptoms

Neutropenia itself causes no symptoms. Problems come from infections, and these can look milder than they are because there are too few neutrophils to cause the usual swelling and pus. Watch for:

• fever, sometimes the only sign
• chills and sweats
• sore throat, mouth ulcers and swollen, sore gums
• cough or shortness of breath
• burning on urination
• redness, pain or swelling around a cut, catheter site or the anus
• diarrhea

Causes of neutropenia

Reduced production in the bone marrow

• Chemotherapy and radiation therapy: the most common cause of severe neutropenia. Counts usually reach their lowest point (the nadir) about 7 to 14 days after a chemotherapy dose.
• Medicines: antithyroid drugs (methimazole, propylthiouracil), clozapine, sulfasalazine, some antibiotics (such as trimethoprim-sulfamethoxazole and high-dose beta-lactams), some antiseizure drugs and others. A sudden fall to almost zero is called agranulocytosis.
• Nutritional deficiencies: vitamin B12, folate or copper deficiency.
• Bone marrow diseases: aplastic anemia, myelodysplastic syndrome, leukemia, lymphoma or cancer spreading to the marrow.
• Inherited disorders: severe congenital neutropenia and cyclic neutropenia, in which counts drop roughly every 21 days.

Increased destruction or use

• Infections: viral infections such as flu, Epstein-Barr virus, hepatitis and HIV often cause temporary neutropenia. Overwhelming bacterial infection and sepsis can use up neutrophils faster than they are made.
• Autoimmune neutropenia: antibodies destroy neutrophils, on its own or with lupus or rheumatoid arthritis (Felty syndrome).
• Enlarged spleen: traps and destroys blood cells.

Normal variation: Duffy-null associated neutrophil count

Many people of African, Middle Eastern and West Indian ancestry have naturally lower neutrophil counts without any increase in infections. This was formerly called "benign ethnic neutropenia" and is linked to the Duffy-null blood group. Lab ranges based on other populations can wrongly flag these counts as abnormal, so it is important that clinicians recognize it to avoid unnecessary tests or withholding treatments.

Diagnosis

• Repeat CBC with differential to confirm the count, and often repeated twice weekly for several weeks if cyclic neutropenia is suspected.
• Review of medicines and recent infections.
• Blood smear to look at cell shapes.
• B12, folate and copper levels; HIV and hepatitis tests; autoimmune tests.
• Duffy blood group testing where relevant.
• Bone marrow biopsy if the cause is unclear, the neutropenia is severe or persistent, or other blood counts are also low.
• Genetic testing for suspected congenital forms.

Treatment

Treat the cause

Stopping a causative medicine usually lets the count recover within 1 to 3 weeks. Replacing B12 or folate, treating an infection or managing an autoimmune disease often corrects the count.

Fever with neutropenia (febrile neutropenia)

This is a medical emergency in people with severe neutropenia. Guidelines call for broad-spectrum intravenous antibiotics as soon as possible, ideally within 1 hour of arrival. Blood cultures and other tests are taken first if this does not delay treatment. Some lower-risk adults can be treated with oral antibiotics and close follow-up after assessment.

Growth factor injections

Granulocyte colony-stimulating factor (G-CSF), such as filgrastim or pegfilgrastim, stimulates the bone marrow to make neutrophils. It is used to prevent neutropenia after chemotherapy with a high risk of it, to speed recovery, and long-term for congenital and some chronic neutropenias.

Other options

Stem cell transplant for severe congenital neutropenia or bone marrow failure. Treatments for the underlying blood disease.

Protecting yourself when your count is low

• Wash your hands often, and ask visitors to do the same.
• Avoid people with colds, flu or other infections, and large crowds when counts are lowest.
• Follow safe food handling: cook meat and eggs thoroughly, wash produce, avoid unpasteurized dairy and juices.
• Do not take your temperature rectally or use suppositories, which can injure the bowel lining.
• Keep your mouth clean with a soft toothbrush.
• Avoid cleaning litter boxes, bird cages or fish tanks.
• Keep a thermometer at home and know your cancer team's 24-hour number.
• Ask about inactivated vaccines such as flu and COVID-19 vaccines, usually given before chemotherapy cycles.

Do not take acetaminophen (paracetamol) or ibuprofen to treat a fever before calling your team, as this can hide an infection.

Frequently asked questions

What is a dangerously low neutrophil count?

An absolute neutrophil count below 500 cells/µL is severe neutropenia and carries a high risk of serious infection, especially if it lasts more than a week. Below 100 is profound. At these levels, any fever of 38 °C (100.4 °F) or more needs emergency medical care.

What causes low neutrophils in a healthy person?

Common causes are a recent viral infection, a medicine, a mild vitamin B12 or folate deficiency, or a normal genetic variant such as Duffy-null associated neutrophil count, which is common in people of African and Middle Eastern ancestry. A repeat test and a medicine review are usually the first steps.

Is neutropenia a sign of cancer?

Usually not. Most mild neutropenia is caused by infections, medicines or normal variation. Neutropenia can occasionally be a sign of leukemia, lymphoma or myelodysplastic syndrome, especially when red cells or platelets are also low, or with weight loss and swollen lymph nodes. Persistent unexplained neutropenia should be investigated.

How long does it take for neutrophils to recover after chemotherapy?

Counts usually fall to their lowest about 7 to 14 days after a chemotherapy dose and recover over the following 1 to 2 weeks, often in time for the next cycle. Growth factor injections shorten this period. Your oncology team checks blood counts before each cycle.

What is febrile neutropenia?

Febrile neutropenia is a fever, usually 38.3 °C (101 °F) once or 38 °C (100.4 °F) for an hour, in someone with an absolute neutrophil count below 500. It is a medical emergency because infections can progress rapidly to sepsis. Intravenous antibiotics are started within an hour of arrival at the hospital.