What is the most common cause of neutropenia?

September 25, 2025 •

4 min read

According to the American Cancer Society, neutropenia is a common and often expected side effect of cancer treatments like chemotherapy. Identifying what is the most common cause of neutropenia, however, requires looking at a broader range of factors, as it varies depending on the patient's overall health and circumstances.

Quick Summary

The most frequent causes of neutropenia include certain medications, particularly chemotherapy, as well as various infections (viral and bacterial) and autoimmune disorders. The specific cause is determined by the patient's individual clinical context.

Key Points

Medication side effects are a top cause: Chemotherapy is a very common trigger for neutropenia in oncology patients, but many other medications can also lead to a low neutrophil count.
Infections are a frequent culprit: Both viral (like HIV, EBV, hepatitis) and bacterial infections can cause neutropenia by suppressing bone marrow or increasing neutrophil destruction.
Autoimmune disorders play a role: Conditions such as lupus and rheumatoid arthritis can prompt the immune system to attack and destroy healthy neutrophils.
Bone marrow problems are a serious concern: Underlying conditions affecting the bone marrow, including leukemia and myelodysplastic syndromes, can directly impair neutrophil production.
Diagnosis requires professional evaluation: Because the causes are so varied, a thorough medical assessment is crucial to determine the specific cause and guide appropriate treatment.
Nutrient deficiencies can contribute: A lack of essential vitamins like B12 and folate can impact bone marrow function and lead to neutropenia.

Understanding Neutropenia

Neutropenia is a condition defined by an abnormally low number of neutrophils, a vital type of white blood cell that defends the body against infections, especially bacterial and fungal ones. This condition can range in severity from mild to life-threatening. A decrease in neutrophils can be a temporary problem, such as following a viral infection, or it can be a persistent issue stemming from chronic disease or treatment.

While identifying the single most common cause can be difficult due to variations in patient populations, medical context, and severity, several factors consistently rank at the top. The causes of neutropenia can be generally categorized into issues with production (the bone marrow doesn't make enough), increased destruction (the body attacks or uses up neutrophils faster than it can replace them), or sequestration (neutrophils are trapped in an organ like the spleen).

Leading Causes of Neutropenia

Medications and Chemotherapy

One of the most widely recognized and common causes of neutropenia is the side effect of certain medications. This is particularly true for cytotoxic chemotherapy used to treat cancer. Chemotherapy drugs are designed to kill rapidly dividing cells, which includes not only cancer cells but also the healthy, fast-dividing cells in the bone marrow that produce neutrophils. As a result, many cancer patients experience a predictable, temporary drop in their neutrophil count following treatment.

However, chemotherapy is not the only medication that can cause this condition. A wide array of other drugs have been implicated, including:

Antibiotics: Certain types, such as some penicillins and cephalosporins, can trigger an immune-mediated destruction of neutrophils or suppress bone marrow.
Antipsychotic drugs: Clozapine is a well-known example with a documented risk of inducing neutropenia.
Anticonvulsants: Some seizure medications can cause a low neutrophil count.
Cardiovascular drugs: Certain medications for heart conditions can have this as a side effect.
Antithyroid medications: Used to treat hyperthyroidism, these can cause neutropenia in some individuals.

Infections

Both viral and bacterial infections can cause a low neutrophil count. The mechanism often involves either direct suppression of the bone marrow or the rapid consumption of neutrophils as the immune system fights the infection. While the neutropenia from an acute infection is often short-lived, it can be severe. Notable infectious causes include:

Viral Infections: Epstein-Barr virus (mononucleosis), cytomegalovirus (CMV), HIV, hepatitis viruses (A, B, and C), influenza, and measles.
Bacterial Infections: In severe cases of systemic infection, or sepsis, the rapid usage of neutrophils can lead to a dangerously low count. Specific bacterial infections like salmonellosis and tuberculosis are also known culprits.

Autoimmune Disorders

In some cases, the body's own immune system mistakenly attacks its neutrophils. This is known as autoimmune neutropenia (AIN) and can be primary (isolated) or secondary to other systemic autoimmune diseases. Secondary AIN is more common in adults and can be associated with conditions such as:

Systemic Lupus Erythematosus (Lupus): A chronic inflammatory disease where the immune system attacks various tissues and organs.
Rheumatoid Arthritis (RA): In some patients with RA, the combination of neutropenia and an enlarged spleen is known as Felty's syndrome.
Other Collagen Vascular Diseases: Sjogren's syndrome and mixed connective tissue disease can also be associated with AIN.

Bone Marrow Disorders

Problems within the bone marrow, where blood cells are produced, can directly lead to neutropenia by hindering the production of new neutrophils. These can be benign or malignant and include:

Leukemia and Lymphoma: Cancers that involve the blood and bone marrow can crowd out the normal blood-forming cells.
Myelodysplastic Syndromes (MDS): A group of disorders where the bone marrow produces abnormal blood cells, leading to low counts.
Aplastic Anemia: A rare but serious condition where the bone marrow stops producing enough new blood cells.

Other Contributing Factors

Nutritional Deficiencies

A lack of certain key nutrients can also impair the bone marrow's ability to produce neutrophils. Deficiencies in vitamins like B12 and folate, as well as minerals such as copper, can contribute to neutropenia.

Congenital and Genetic Syndromes

Though rare, some people are born with a predisposition to neutropenia due to genetic mutations affecting neutrophil production. Examples include severe congenital neutropenia and cyclic neutropenia.

Differential Diagnosis

Given the wide range of potential causes, a healthcare provider will conduct a thorough investigation, including a complete blood count (CBC) with differential, to determine the underlying issue.

Comparing Common Causes of Neutropenia


Cause Category	Example Conditions	Mechanism
Medication Effects	Chemotherapy, some antibiotics, antipsychotics	Bone marrow suppression or immune-mediated destruction of neutrophils
Infections	Viral (HIV, EBV, influenza), Bacterial (sepsis, typhoid)	Increased peripheral destruction or consumption of neutrophils
Autoimmune Disorders	Lupus, Rheumatoid Arthritis, Felty's Syndrome	Immune system produces antibodies that attack healthy neutrophils
Bone Marrow Disorders	Leukemia, Myelodysplastic Syndrome, Aplastic Anemia	Malignant or abnormal cells interfere with normal neutrophil production
Nutritional Deficiencies	Vitamin B12 deficiency, Folate deficiency	Impaired blood cell production due to lack of essential nutrients

Conclusion: Finding the Root Cause is Key

While many people associate neutropenia with cancer and chemotherapy, the condition has a diverse set of possible causes, ranging from temporary viral infections to chronic autoimmune diseases and inherited conditions. Because the treatment for neutropenia is highly dependent on the underlying cause, a comprehensive medical evaluation is necessary for an accurate diagnosis and effective management plan. For many patients, managing the primary condition or adjusting medication is sufficient to resolve the low neutrophil count.

For more in-depth information on managing neutropenia, especially during cancer treatment, consult resources from authoritative health organizations like the National Cancer Institute or the American Cancer Society, as they provide detailed guidance and patient support. Link to CancerCare on Neutropenia

Frequently Asked Questions

The most common causes of neutropenia in children vary. Temporary neutropenia is often caused by infections, but some children may have chronic benign neutropenia, a form that typically resolves on its own within a few years.

Yes, many non-chemotherapy medications can cause neutropenia. Examples include some antibiotics, certain antipsychotics like clozapine, and antithyroid drugs. The effect can be immune-mediated or due to bone marrow suppression.

No, neutropenia is not always related to cancer. While chemotherapy is a very common cause, infections, autoimmune disorders, and inherited conditions are also frequent causes. Many cases are not linked to cancer at all.

A doctor will typically perform a complete blood count (CBC) with differential to confirm neutropenia. They will then review a patient's medical history, current medications, recent infections, and perform a physical exam. Further tests like a bone marrow biopsy may be needed if the cause is not apparent.

Infections can lead to neutropenia in two main ways: either by directly suppressing bone marrow production of neutrophils or by overwhelming the body's immune response, leading to a rapid consumption of neutrophils that outpaces production.

Untreated neutropenia, especially severe cases, leaves the body highly susceptible to serious bacterial and fungal infections. Even common bacteria can cause severe illness. It is crucial to manage the underlying cause to prevent life-threatening complications.

Yes, drug-induced neutropenia is often reversible. In many cases, stopping the offending medication or adjusting the dosage can allow the neutrophil count to recover and return to normal.