What are the causes of neutropenia (low neutrophil count)?

From the Guidelines

Neutropenia, or low neutrophil count, is commonly caused by several factors including bone marrow disorders, certain medications, infections, autoimmune conditions, and nutritional deficiencies. Medications that frequently cause neutropenia include chemotherapy drugs, antibiotics like trimethoprim-sulfamethoxazole, antipsychotics such as clozapine, and some anti-inflammatory medications. Viral infections like HIV, hepatitis, or influenza can suppress neutrophil production, while bacterial infections may consume neutrophils faster than they can be produced. Bone marrow disorders such as leukemia, myelodysplastic syndromes, and aplastic anemia directly affect neutrophil production. Autoimmune conditions like lupus or rheumatoid arthritis can trigger neutrophil destruction. Severe vitamin B12 or folate deficiencies impair proper neutrophil development. Genetic disorders like congenital neutropenia or cyclic neutropenia can also cause chronically low neutrophil counts. Treatment depends on identifying and addressing the underlying cause, which may involve stopping offending medications, treating infections, or managing autoimmune conditions. In severe cases with high infection risk, granulocyte colony-stimulating factors like filgrastim may be prescribed to stimulate neutrophil production, as supported by the most recent guidelines 1.

Some key points to consider:

• The use of hematopoietic growth factors such as G-CSF or its pegylated form should be reserved for patients at high risk of febrile neutropenia or those with special circumstances, as recommended by the ESMO guidelines 1.
• G-CSF can be effective in treating severe chronic neutropenia, including cyclic, congenital, and idiopathic neutropenia, with dosages adjusted to maintain a blood neutrophil level in the normal or low normal range 1.
• Patients with severe congenital neutropenia are at risk of developing myelodysplasia and leukemia, with or without G-CSF treatment, emphasizing the importance of making a correct diagnosis and following these patients carefully 1.

Overall, the management of neutropenia requires a comprehensive approach that takes into account the underlying cause and the individual patient's risk factors, as well as the potential benefits and risks of treatment with granulocyte colony-stimulating factors.

From the FDA Drug Label

• Patients with cancer undergoing bone marrow transplantation • Patients with congenital neutropenia • Patients with cyclic or idiopathic neutropenia • Patients acutely exposed to myelosuppressive doses of radiation

The causes of neutropenia (low neutrophil count) include:

• Cancer undergoing bone marrow transplantation 2
• Congenital neutropenia 2
• Cyclic or idiopathic neutropenia 2
• Myelosuppressive doses of radiation 2

From the Research

Causes of Neutropenia

The causes of neutropenia can be categorized into several groups, including:

• Congenital conditions, such as benign familial neutropenia and severe congenital neutropenia (e.g., Kostmann disease) 3
• Acquired conditions, including:
  • Medication-induced neutropenia, which can be caused by a variety of drugs, such as dipyrone, diclofenac, and antithyroid drugs 4
  • Autoimmune disorders, such as rheumatoid arthritis-related autoimmune reaction 5
  • Infections, such as HIV and hepatitis 3
  • Malignancies, such as multiple myeloma 6
• Other causes, including:
  • Folic acid deficiency, particularly in patients taking methotrexate 5
  • Splenomegaly, which can be associated with Felty's syndrome and large granular lymphocytic leukemia 5

Mechanisms of Neutropenia

The mechanisms of neutropenia can vary depending on the underlying cause, but may include:

• Decreased neutrophil production, which can be caused by bone marrow failure or suppression 6
• Accelerated neutrophil destruction, which can be caused by autoimmune disorders or medication-induced neutropenia 4
• Shift in compartments of neutrophils, which can be caused by infection or inflammation 6

Risk Factors for Neutropenia

Certain patient characteristics and disease factors can increase the risk of developing neutropenia, including:

• Chemotherapy-related high-risk factors, such as regimens with an expected neutropenia rate of > 50% 6
• Patient characteristics, such as disease stage and type of current and previous treatment 6
• Low absolute neutrophil count (ANC) at baseline, which can increase the risk of severe neutropenia 6