What Is Agranulocytosis?

White blood cells are the powerhouse of the immune system. There are several types of white blood cells, and each does a particular job. One type of white blood cells is called granulocytes.

This group of white blood cells—which includes neutrophils that fight bacterial infections, eosinophils that fight parasitic infections, and basophils that respond to allergens—releases tiny particles filled with enzymes during infections, allergic reactions, and asthma.

For most of us, the number of white blood cells like granulocytes that circulate in the body increase when you are fighting an infection. Some people have too few granulocytes, though, and this can result in agranulocytosis. This condition can put you at risk for developing severe infections.

Types of Agranulocytosis

There are two main types of agranulocytosis. You are either born with it, or you acquire the condition later on:

• Congenital agranulocytosis: Congenital agranulocytosis is sometimes referred to as Kostmann's syndrome. It is a disease of the bone marrow, the spongy part at the center of your bones, that is inherited through a genetic mutation. Children with this condition are born without neutrophils. This can lead to frequent and severe infections, bone diseases, and even leukemia (blood cancer). There is no cure, but people with this condition may be given medications to boost the number of other blood cells or to help fight infections.
• Acquired agranulocytosis: Acquired agranulocytosis occurs when your number of granulocytes drops because of a medication or condition.

Symptoms

Agranulocytosis does not cause any symptoms. You may not notice a drop in your white blood count, but you will feel the result of that drop: an infection. Common symptoms of an infection include:

• Fever
• Chills
• Increased heart rate
• Faster breathing
• A sudden drop in blood pressure
• Weakness
• Fatigue
• Dizziness
• Sores in the mouth and throat
• Bleeding gums

Causes

There is really only one cause for congenital agranulocytosis: genetic mutation. Acquired agranulocytosis, on the other hand, can develop because of:

• Autoimmune diseases like lupus (affects many different body systems)
• Bone marrow diseases
• Chemotherapy (drugs that kill cancer cells)
• Mercury or lead exposure
• Infections like tuberculosis (infectious disease affecting the lungs) or viral infections
• Vitamin deficiencies
• Medications

Many times, the medications that are to blame for the development of this condition are cancer drugs that suppress the activity in your bone marrow. However, many medications can lead to this reaction, including some antipsychotic medications like Clozaril (clozapine).

Clozaril is often used to treat conditions like the serious mental health disorder schizophrenia, and it has been linked to the development of agranulocytosis, usually within the first few weeks of treatment.

While death from agranulocytosis in people who developed the condition after taking Clozaril is rare, people who take this medication appear to develop the condition more often than people taking other types of drugs. According to one study, about one in 250 people taking Clozaril developed agranulocytosis.

Diagnosis

Diagnosis of agranulocytosis is typically made with a blood test. Your doctor may order testing if you have been experiencing frequent, severe infections or if you are at risk because of an underlying condition or the medications you are taking.

The blood test that is usually ordered is a complete blood count (CBC), along with an absolute neutrophil and differential count. A CBC will count the number of red and white blood cells in a sample, but the neutrophil and differential counts provide information on how much of each type of white blood cell you have.

Agranulocytosis is essentially a severe form of neutropenia, when you have too many neutrophils, but these conditions are classified differently depending on how low your neutrophil count becomes.

The ranges of neutrophil count are:

• Normal neutrophil count: 2,500–6,000 neutrophils per microliter
• Neutrophil count with neutropenia: Less than 1,500 neutrophils per microliter
• Neutrophil count with agranulocytosis: Less than 100 neutrophils per microliter

Treatment

One of the main ways acquired agranulocytosis is treated is to stop taking the medication that is causing it. If it's a chemotherapy medication that is causing your white blood cell count (WBC) to drop, you and your doctor will discuss the risks and benefits of continuing vs. stopping your treatment.

If stopping a medication isn't the answer, there are some drugs that can help your body produce more white blood cells faster, like granulocyte colony-stimulating factor (G-CSF) medications.

Outside of addressing the cause of your agranulocytosis, your doctor will talk to you about preventing infection. This can include:

• Taking antibiotics
• Wearing a face mask in public
• Frequent handwashing
• Avoiding crowds

If stopping these treatments doesn't help, you may need to consider undergoing a bone marrow transplant. With this procedure, you will receive bone marrow from a donor that matches your tissue type. After the bone marrow is transplanted, it will help repopulate your body with healthy cells.

Prognosis

Agranulocytosis is generally a treatable condition. People who have a higher risk of developing complications or even dying because of agranulocytosis include people who:

• Are over age 65
• Have kidney problems
• Have heart problems
• Have breathing problems
• Have multiple health issues

People who are taking Clozaril are more likely to develop agranulocytosis than people who take other medications, but they are less likely to die from this condition. Mortality rates for agranulocytosis from Clozaril are around 3%, while mortality rates from agranulocytosis caused by other medications are between 7% and 10%, according to one study.

Coping

Managing conditions like agranulocytosis can be challenging because you may have to avoid some activities that you enjoy. People who deal with low WBC report a general lower quality of life, as well as symptoms like:

• Anger
• Anxiety
• Pain
• Fatigue
• Mobility problems
• Social and peer problems

Finding people who share your experience, either through your health system or a support group, can help. You may also want to ask people you are around a lot to try to prevent acquiring an infection too, such as by getting vaccinated or taking other precautions.

Some other ways you can cope with agranulocytosis include:

• Get vaccinated against some infections.
• Avoid live vaccines.
• Cook all your food well.
• Keep hot foods hot and cold foods cold.
• Avoid raw fruits and vegetables.
• Wash raw foods well before eating them.
• Limit contact with animals.

If you develop an infection and have been diagnosed with agranulocytosis, check in with your doctor regularly. It's important to manage the infection early before it becomes more severe, possibly resulting in sepsis, your body's extreme response to an infection throughout the body or even death.

Summary

Agranulocytosis occurs when you have a low level of granulocytes, a type of white blood cells that release particles filled with enzymes during an infection, allergic reaction, or asthma. This condition doesn't cause any symptoms, but it will increase your risk of infections, which will cause symptoms like fever, chills, headaches, and body aches.

The only way to find out if you have agranulocytosis is through a blood test called a complete blood count. You will want to practice strategies to prevent infections like washing your hands frequently.

A Word From Verywell

A weakened immune system can limit your activities. Conditions like agranulocytosis decrease the amount of white blood cells your body has to fight infection, making you more prone to severe infection and even death. This problem can be present at birth or develop because you have a certain disease or are taking medication. Talk to your doctor about how to protect yourself and boost your immune system if you develop this condition.

Frequently Asked Questions 

When will you know if you have agranulocytosis?

If you are having frequent or severe infections and have a condition or medication that can lower your white blood cell count, talk to your doctor about being tested. In some cases, such as during cancer treatment, your blood counts will be monitored throughout the process as a part of your treatment plan.

How does agranulocytosis differ from neutropenia?

Agranulocytosis is a more severe form of neutropenia, which is when you have a low level of white blood cells called neutrophils. With neutropenia, you have less than 1,000 neutrophils, but with agranulocytosis you have less than 100.

Does Clozaril cause agranulocytosis?

Yes. A number of medications can cause agranulocytosis, and Clozaril is one of them. Talk to your doctor if you have started taking this medication and become ill or get an infection. Most cases of agranulocytosis from Clozaril develop in the first few months after you start treatment.

What happens when you have a low white blood cell count?

When you have a low white blood cell count, you have a lower-than-normal number of cells that fight infection. A simple cold or injury can turn into something much more serious when your white blood cell count is low.