Agranulocytosis

Overview

What is agranulocytosis?

Agranulocytosis is a life-threatening blood disorder. It happens when the body doesn’t make enough of a type of white blood cells called neutrophils. White blood cells are part of the immune system. They protect the body from infection by fighting off germs that make us sick.

Also known as granulocytopenia, agranulocytosis is a severe form of neutropenia. Neutropenia is lower-than-normal levels of white blood cells. People with a low white blood cell count are very vulnerable to infection. They may get sick from germs that wouldn’t be harmful otherwise. Healthcare providers can treat agranulocytosis with medications. Untreated, the condition can lead to severe infections. It can even lead to sepsis (a severe reaction to infection) and death.

What are the types of agranulocytosis?

There are two types of agranulocytosis. It can be inherited (present at birth) or acquired.

  • Inherited agranulocytosis results from a genetic disorder. This problem affects how the body produces white blood cells. Infantile genetic agranulocytosis is a rare form of inherited agranulocytosis. It is also called Kostmann syndrome or congenital agranulocytosis. Newborns with this condition have recurring infections, fevers, inflammation and problems with their bones.
  • Acquired agranulocytosis can result from certain infections. Exposure to chemicals and some prescription medications may also cause it. Cancer-treating drugs and antipsychotic medications commonly cause acquired agranulocytosis. This form of the disorder is also called drug-induced agranulocytosis.

How common is agranulocytosis?

Agranulocytosis affects about seven people of every 1 million each year. It’s slightly more common in women. People of all ages can get the condition.

Inherited agranulocytosis is more common among babies and children. The acquired form appears more often in adults.

Agranulocytosis is more common among people who:

  • Are undergoing chemotherapy treatments for cancer.
  • Have autoimmune diseases such as lupus or rheumatoid arthritis.
  • Take certain prescription drugs, such as the antipsychotic medication clozapine (Clozaril®).

Symptoms and Causes

What causes agranulocytosis?

Granulocytes are white blood cells that are part of your immune system. These cells contain enzymes that kill germs and break down substances that may harm your body. There are three types of granulocytes: neutrophils, eosinophils and basophils.

Agranulocytosis happens when the levels of neutrophils are dangerously low. If you don’t have enough neutrophils, you’re at risk of frequent or chronic (long-term) infections. Your risk of severe infection increases over time if neutrophil levels remain low.

What causes acquired agranulocytosis?

Several types of prescription medications cause acquired agranulocytosis. Infections, other health conditions and exposure to chemicals can also lead to the disorder. Causes of agranulocytosis include:

  • Autoimmune disorders, including lupus and rheumatoid arthritis.
  • Bone marrow disease and bone marrow failure disorders like aplastic anemia.
  • Chemotherapy.
  • Exposure to toxins or chemicals, such as lead or mercury.
  • Infections such as malaria, tuberculosis and Rocky Mountain spotted fever.
  • Prescription drugs, including some antibiotics, antipsychotic medications and drugs to treat thyroid problems.
  • Poor nutrition and vitamin deficiencies.

What are the symptoms of agranulocytosis?

Agranulocytosis itself doesn’t have symptoms. People with the disorder have symptoms of infection. Signs of agranulocytosis may appear suddenly or gradually. They include:

  • Fever and chills.
  • Faster heart rate and breathing.
  • Sudden low blood pressure (hypotension), which can make you feel lightheaded or weak.
  • Muscle weakness and fatigue.
  • Sore mouth and throat and bleeding, inflamed gums.
  • Ulcers (sores) in the mouth and throat that make it difficult to swallow.

Diagnosis and Tests

How is agranulocytosis diagnosed?

Neutrophils are a type of white blood cell that fights infections in the body. Agranulocytosis occurs when the absolute neutrophil count (ANC) is less than 100 neutrophils per microliter of blood. Usually, people have at least 1,500 neutrophils per microliter.

To diagnose agranulocytosis, your provider will order a blood test. This test, called a complete blood count (CBC), checks neutrophil levels in your blood. Your healthcare provider may also take a sample of your bone marrow to evaluate how your body produces white blood cells. Your provider will also ask about your symptoms, medications, recent infections and chemical exposure. If your provider believes you have the inherited form of the disease, you may need a genetic test.

Management and Treatment

How is agranulocytosis treated?

If a prescription medication is causing your symptoms, it’s essential to stop taking the medicine. Talk to your provider about how to stop safely. Agranulocytosis treatment includes:

  • Antibiotics: If you have an infection, your healthcare provider will prescribe antibiotics and other medications to relieve your symptoms.
  • Granulocyte colony-stimulating factor (G-CSF): Your provider may recommend injections of a drug to help your body produce white blood cells, specifically neutrophils, faster. Your provider may prescribe filgrastim (Neupogen®), pegfilgrastim (Neulasta®) or lenograstim (Granocyte®).
  • Immunosuppressant drugs: If an autoimmune disorder causes agranulocytosis, your provider may recommend medicines such as prednisone. These medications suppress (calm down) the immune system.
  • Bone marrow transplant: If other treatments aren’t effective, you may need a bone marrow transplant. During this procedure, you receive bone marrow from a donor so you can produce more white blood cells.
  • Preventing infection: People with agranulocytosis should be careful to avoid infection. Wash your hands often, avoid crowds and wear a face covering in public.

Prevention

Can I prevent agranulocytosis?

You may not be able to prevent agranulocytosis. If you’re taking a prescription medication that lowers your white blood cell count, talk to your provider. You may need regular blood tests to track how many neutrophils your bone marrow produces. If you’re having chemotherapy for cancer, your healthcare provider may recommend injections to improve your body’s ability to make white blood cells.

Outlook / Prognosis

What is the outlook for people who have agranulocytosis?

Agranulocytosis is treatable with medication, but the outlook varies from person to person. Adults over 65 are more likely to experience complications such as sepsis. Agranulocytosis can cause severe problems in people who have other health conditions, such as kidney disease, heart disease or breathing problems.

Untreated, agranulocytosis leads to severe infection and death. The risk of infection increases the longer the neutrophil count remains dangerously low.

Living With

When should I see my healthcare provider about agranulocytosis?

Agranulocytosis is life-threatening. It’s essential to seek diagnosis and treatment right away. If you have signs of infection, see your provider. Tell your provider if you have frequent infections or infections that last a long time.

A note from Cleveland Clinic

Agranulocytosis is a serious disorder, but it is treatable. Tell your provider right away if you have signs of infection, especially if you have infections that come and go frequently. If you have an autoimmune disorder or take a prescription medication that decreases white blood cells, it’s very important to see your provider often. With regular checkups, your provider can monitor your health and help you avoid infection.

Last reviewed by a Cleveland Clinic medical professional on 11/25/2020.

References

  • Merck Manuals. Neutropenia. (https://www.merckmanuals.com/home/blood-disorders/white-blood-cell-disorders/neutropenia) Accessed 12/7/2020.
  • National Organization for Rare Disorders. Agranulocytosis, Acquired. (https://rarediseases.org/rare-diseases/agranulocytosis-acquired/) Accessed 12/7/2020.
  • Sedhai YR, Lamichhane A, Gupta V. Agranulocytosis. (https://www.ncbi.nlm.nih.gov/books/NBK559275/) [Updated 2020 Jun 9]. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2020 Jan. Accessed 12/7/2020.

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