Neutrophilic granulocytes (or neutrophils) are the most abundant circulating leukocytes in humans which play a fundamental role in the innate immune response. These cells are recruited rapidly when inflammation is present, and their primary role is to kill invading microorganisms via phagocytosis by release of preformed granular enzymes and proteins, as well as by the production of a range of oxygen species.

Neutropenia can be defined as the reduction in the absolute number of neutrophils in the blood circulation. The condition can be acute or chronic, and is most often seen as a result of autoimmune disorders, chemotherapy treatments or adverse drug reactions, although it can be also seen as a part of congenital neutropenia syndromes.

Homeostatic regulation of blood neutrophil counts

Stable neutrophil blood counts are not static, but rather a result of a highly dynamic feedback system. Neutrophil homeostasis is maintained by a delicate balance between granulopoiesis (production of granulocytes), bone marrow storage and release, margination in blood vessels, clearance and destruction.

Neutrophils are produced inside the hematopoietic cords interspersed within the venous sinuses of the bone marrow. The differentiation of granulocytes is regulated by the synchronized expression of fundamental myeloid transcription factors, with granulocytes and macrophages differentiating from a common progenitor cell.

Neutrophil counts in healthy humans are regulated by a myriad of environmental and genetic factors, most of which still remain unknown. The presence of severe neutropenia highlights the vital role of the neutrophil, with its panoply of defense mechanisms used to contain and kill pathogenic microorganisms.

Definition and epidemiology of neutropenia

According to the general guidelines, neutropenia can be characterized clinically as mild neutropenia with an absolute neutrophil count of 1000-1500/μL, moderate neutropenia with an absolute neutrophil count of 500-1000/μL, or severe neutropenia with an absolute neutrophil count of less than 500/μL.

The exact definition of febrile neutropenia varies, but is generally defined as the presence of a fever higher than 38.3°C with an absolute neutrophil count less than 1000/μL. It is one of the most serious adverse events in patients with hematological malignancies undergoing chemotherapy, and potential rapid progression of infections makes it a true medical emergency.

Neutropenia is often a secondary finding in a patient who has significant underlying hematologic disorders. Acute neutropenia arises swiftly when neutrophil use is rapid and production impaired; conversely, chronic neutropenia is a result of reduced production, increased destruction or excessive splenic sequestration of neutrophils, often lasting three months or more.

According to the French National Registry of Primary Immunodeficiency Diseases, all cases of congenital neutropenia occur at 6.2 cases per million. Febrile neutropenia continues to represent a significant cause of morbidity, mortality and economic loss in patients receiving cancer chemotherapy.

Care for patients with neutropenia is mostly based on supportive measures, taking into account the cause, severity, and duration of the neutropenia. Fever and various infections that occur as complications of neutropenia necessitate specific and targeted treatment. Surgical approach is usually not indicated, albeit it may be employed in certain contexts.

Further Reading

• All Neutropenia Content
• What Causes Neutropenia?
• Neutropenia Diagnosis
• Neutropenia Symptoms
• Absolute Neutrophil Count (ANC)

Written by

Dr. Tomislav Meštrović

Dr. Tomislav Meštrović is a medical doctor (MD) with a Ph.D. in biomedical and health sciences, specialist in the field of clinical microbiology, and an Assistant Professor at Croatia's youngest university – University North. In addition to his interest in clinical, research and lecturing activities, his immense passion for medical writing and scientific communication goes back to his student days. He enjoys contributing back to the community. In his spare time, Tomislav is a movie buff and an avid traveler.