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

From the Guidelines

Neutropenia is primarily caused by a decrease in neutrophils due to various factors including certain medications, viral infections, bacterial or fungal infections, autoimmune disorders, bone marrow disorders, nutritional deficiencies, congenital disorders, and radiation exposure. The most common causes of neutropenia include:

• Certain medications such as chemotherapy drugs, antibiotics like trimethoprim-sulfamethoxazole, antipsychotics, and some anti-seizure medications
• Viral infections like HIV, hepatitis, and influenza
• Bacterial or fungal infections
• Autoimmune disorders such as lupus and rheumatoid arthritis
• Bone marrow disorders like leukemia and myelodysplastic syndromes
• Nutritional deficiencies including vitamin B12 or folate deficiency
• Congenital disorders like Kostmann syndrome and cyclic neutropenia
• Radiation exposure Neutropenia can also be induced by hypersplenism, where an enlarged spleen traps and destroys blood cells. The severity of neutropenia is classified based on the absolute neutrophil count (ANC), with severe neutropenia (ANC < 500 cells/μL) posing the highest risk for infections, as noted in the study by 1. Treatment depends on the underlying cause and may include granulocyte colony-stimulating factors like filgrastim (Neupogen) to stimulate neutrophil production, antibiotics for infections, and addressing the primary condition causing the neutropenia, as discussed in the guidelines by 1. It is essential to prioritize the management of febrile neutropenia, as it can lead to severe complications and mortality, with a hospital mortality rate of up to 11% as reported in the study by 1. Therefore, prompt initiation of empirical antibiotic therapy is crucial in patients with fever and neutropenia, as recommended by the guidelines by 1.

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 and its treatment, such as bone marrow transplantation and myelosuppressive doses of radiation
• Congenital neutropenia, a condition present at birth
• Cyclic or idiopathic neutropenia, a condition where the neutrophil count fluctuates or is low for unknown reasons 2

From the Research

Causes of Neutropenia

• Drug-induced neutropenia, which can be immune-mediated or due to direct inhibition of bone marrow precursors 3
• Autoimmune neutropenia, caused by granulocyte-specific autoantibodies, which occurs predominantly in infancy 4
• Chemotherapy-induced neutropenia, which can be profound and require hospitalization 5
• Viral infections, which can occur during periods of neutropenia, particularly after bone marrow transplantation 6
• Congenital marrow defects, intrinsic and acquired disorders, which can cause severe chronic neutropenia 7

Underlying Factors

• Immunosuppressive disease or therapy, which can increase the risk of infection 6
• Defects in cellular immune function, which can predispose to viral infections 6
• Underlying disease and nature of therapy, which can affect the net state of the patient's host-defence mechanisms 6

Clinical Presentation

• Severe neutropenia, defined by an absolute blood neutrophil count (ANC) less than 0.5 x 10(9)/L, which can predispose to infection 7
• Oral ulcers and inflammation, and recurrent skin infections, which are common in severely neutropenic patients 7
• Fever, which can be a symptom of febrile neutropenia 3, 5