From the Guidelines
Neutropenia, or low neutrophil count, is primarily caused by factors such as cancer treatments, particularly chemotherapy, which suppress bone marrow function, as well as certain medications, viral infections, autoimmune disorders, bone marrow disorders, nutritional deficiencies, congenital disorders, and severe bacterial infections, as supported by recent guidelines 1.
Causes of Neutropenia
The causes of neutropenia can be diverse and include:
- Viral infections
- Certain medications, such as chemotherapy drugs, antibiotics like trimethoprim-sulfamethoxazole, and antipsychotics like clozapine
- Autoimmune disorders, including lupus or rheumatoid arthritis
- Bone marrow disorders, like aplastic anemia or myelodysplastic syndromes
- Nutritional deficiencies, especially vitamin B12 and folate
- Congenital disorders
- Severe bacterial infections
- Cancer treatments that suppress bone marrow function where neutrophils are produced
- Certain genetic conditions like Kostmann syndrome that can lead to chronically low neutrophil counts
Classification and Risk
The severity of neutropenia is classified based on the absolute neutrophil count (ANC), with severe neutropenia (ANC below 500 cells/μL) posing the highest risk for infections, as indicated by guidelines for managing febrile neutropenia 1.
Treatment Approach
Treatment depends on identifying and addressing the underlying cause, which may include stopping offending medications, treating infections, or in severe cases, administering granulocyte colony-stimulating factors like filgrastim to stimulate neutrophil production, as recommended by guidelines for myeloid growth factors 1. Key considerations in managing neutropenia include:
- Identifying the underlying cause
- Stopping or adjusting medications that may be contributing to neutropenia
- Treating any underlying infections
- Using granulocyte colony-stimulating factors (G-CSF) in appropriate cases to stimulate neutrophil production
- Monitoring for complications, especially in cases of severe or prolonged neutropenia, as highlighted in guidelines for preventing opportunistic infections 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 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, a condition characterized by a low neutrophil count, can be categorized into several factors, including:
- Decreased neutrophil production 3, 4, 5
- Accelerated use of neutrophils 3
- Shift in compartments of neutrophils 3
- Combination of these factors 3
- Genetic variations or mutations, such as benign familial neutropenia and chronic severe neutropenias (e.g. Kostmann disease) 6
- Underlying disorders, including HIV, hepatitis, autoimmune disorders, and large granular lymphocyte syndrome 6
- Medications, such as those used to treat rheumatoid arthritis, including methotrexate 7
- Folic acid deficiency, particularly in patients taking methotrexate 7
- RA-related autoimmune reaction, including Felty's syndrome and large granular lymphocytic (LGL) leukemia 7
- Constitutional neutropenia, which is rare and usually moderate and well-tolerated, predominantly affecting patients of African descent 7
- Congenital neutropenia due to genetic abnormalities, which is severe and chiefly seen in the pediatric population 7
- Extrinsic causes, including impaired proliferation and maturation of myeloid progenitor cells in the bone marrow 4
- Intrinsic causes, including sequestering of neutrophils and increased destruction of neutrophils in the peripheral blood 5
Classification of Neutropenia
Neutropenia can be classified according to its severity, with mild, moderate, and severe forms 3, 7, 5, as well as its duration, with transient and chronic forms 4. Chronic neutropenia can be further described as extrinsic or intrinsic 4.
Clinical Implications
The clinical result of neutropenia is an increased risk for infection, which is directly proportional to the severity and duration of neutropenia 3, 5. Febrile neutropenia is associated with substantial morbidity and even mortality 5. Assessment of patients with neutropenia should be guided by the severity on presentation, and treatment should be aimed at managing the underlying cause of neutropenia 4.