Agranulocytosis

Agranulocytosis (ay-GRAN-yoo-loh-sy-TOH-sis) is a very rare, life-threatening condition that happens when you have very low levels of neutrophils, a type of granulocyte.

Granulocytes are a group of white blood cells that fight infections. Neutrophils are the most common type of granulocyte. They’re first on the scene when you’re sick. In agranulocytosis, you don’t have enough neutrophils, so your body isn’t able to effectively fight infections. You may develop sepsis.

Types of this condition

The two types of this rare condition are:

• Acquired agranulocytosis: This type happens when something affects your neutrophils. Research shows it may be a very rare side effect of certain medications. Experts estimate acquired agranulocytosis may affect 1 to 7 people out of 1 million.
• Congenital agranulocytosis: This type is present at birth. It’s also known as Kostmann syndrome. The disease happens when a genetic change during fetal development affects how your bone marrow makes neutrophils. Experts estimate 1 in 200,000 babies have this form of agranulocytosis.

This article focuses on acquired agranulocytosis.

Symptoms of agranulocytosis

This condition doesn’t cause symptoms. But it increases your risk of severe infections that may cause symptoms, including:

• Extreme tiredness
• Fever and chills
• Faster heart rate and breathing
• Muscle weakness
• Sore throat and bleeding, inflamed gums
• Sores in your mouth and throat that make it difficult to swallow
• Sudden weakness or feeling lightheaded

Condition causes

A very rare reaction to certain medications can cause acquired agranulocytosis. Healthcare providers may call this drug-induced agranulocytosis. Other causes are conditions that affect your body’s ability to make neutrophils and exposure to toxic substances.

Drug-induced agranulocytosis

Agranulocytosis is a very rare but serious chemotherapy side effect. Researchers link several medications to this condition. Those include:

• Antibiotics: Amoxicillin
• Antifungal medication: Clotrimazole
• Anti-inflammatory medication: Sulfasalazine
• Antipsychotic medication: Clozapine
• Antiviral medication: Valganciclovir
• Pain medication: Metamizole
• Thyroid medications: Carbimazole and thiamazole

It’s important to remember that drug-induced agranulocytosis rarely happens. Talk to your healthcare provider if you have any concerns about side effects. They’ll explain why a drug is part of your treatment plan and what to do if you experience side effects.

Medical conditions

Some conditions attack neutrophils or keep your bone marrow from making them, so you have low neutrophil levels. Examples include:

• Autoimmune diseases: Lupus and rheumatoid arthritis are examples. They cause your immune system to make antibodies that inappropriately attack and destroy your neutrophils
• Bone marrow failure: Some diseases, like aplastic anemia, attack stem cells in your bone marrow. So, the cells don’t become neutrophils. Other diseases, like leukemia or myelodysplastic syndrome, involve abnormal blood stem cells that can’t mature and that crowd out healthy blood stem cells.
• Infections: Bacterial infections, like typhoid fever and tuberculosis, and viral infections, like hepatitis and HIV, can keep your bone marrow from making neutrophils.
• Vitamin deficiency: Vitamin B12 and folate deficiencies, and some other nutrient deficiencies, can affect neutrophil production.

Long-term exposure to lead or mercury may also cause this condition.

Complications of this condition

Sepsis is the most serious complication. It can happen if you have frequent infections or infections that don’t go away. Sepsis is life-threatening. You need medical treatment right away if you have sepsis.

You’re more likely to experience complications with agranulocytosis if you’re over age 65 or if you have other health conditions, like heart, kidney or lung disease.

How doctors diagnose this condition

Healthcare providers will ask about your symptoms and health. For example, they’ll ask if you’ve had recent infections that keep coming back or don’t go away. They’ll ask if you have an autoimmune disease or bone marrow disorder diagnosis. And they’ll ask what prescription medications you take.

A provider will do tests, including:

• CBC with differential: This test checks your neutrophil levels. Agranulocytosis occurs when the absolute neutrophil count (ANC) is fewer than 100 neutrophils per microliter of blood. Normally, people have at least 1,500 neutrophils per microliter.
• Bone marrow biopsy: A provider will get a sample of your bone marrow. A medical pathologist will check neutrophil levels in the sample.
• Genetic testing: You may have tests if your provider thinks you have congenital agranulocytosis.

How is agranulocytosis treated?

Rarely, agranulocytosis is a reaction to medication. In that case, your healthcare provider will prescribe another type. They’ll treat any underlying disease that affects your neutrophils. Here are some examples:

• Antibiotics: If you have an infection, your healthcare provider will prescribe antibiotics and other medications to treat it.
• Immunosuppressants: If an autoimmune disorder causes agranulocytosis, your healthcare provider may recommend medicines that calm your immune system, like prednisone.
• Granulocyte colony-stimulating factor (G-CSF) therapy: This treatment boosts neutrophil production. Your provider may prescribe filgrastim (Neupogen®), pegfilgrastim (Neulasta®) or lenograstim (Granocyte®).
• Stem cell (bone marrow) transplant: Your provider may recommend you have this procedure if other treatments aren’t effective. Donor stem cells help make more neutrophils.

Recovery time

Different things may affect your recovery. If medication causes the condition, it may take one to three weeks after you stop it for your neutrophil levels to return to normal. It will take much more time to recover from a stem cell (bone marrow) transplant.

There are steps you can take to protect your health while your neutrophils bounce back:

• Wash your hands.
• Avoid people who are sick.
• Avoid food poisoning by making and storing food properly.

When should I see my healthcare provider?

Agranulocytosis may start as chills, fever and feeling very tired. Talk to a healthcare provider if you have a fever of 104 degrees Fahrenheit (40 degrees Celsius) or feel very tired for no reason.

Go to the emergency room right away if you have symptoms like:

• Dizziness or feeling lightheaded
• Fast heart rate
• Rapid breathing
• Shortness of breath
• Shaking or chills
• Warm or sweaty skin for no reason
• Weakness

Sepsis causes these symptoms. Without prompt treatment, sepsis can be fatal.

What can I expect if I have this condition?

Stopping the medication that causes agranulocytosis often cures it. Your healthcare provider may recommend frequent checkups to monitor neutrophil levels if you need to take a drug that increases your risk of agranulocytosis.

What’s the difference between agranulocytosis and neutropenia?

Agranulocytosis is a severe form of neutropenia. Neutropenia involves having lower-than-normal levels of white blood cells. People with fewer than 1,500 neutrophils per microliter of blood have neutropenia. People with fewer than 100 neutrophils per microliter of blood have the most severe form of neutropenia, agranulocytosis.