Neutropenia designates a blood absolute neutrophil count that is less than 2 standard deviations (SDs) below the mean of a normal population. Neutropenia can be inherited or acquired. It usually results from decreased production of neutrophil precursor cells in the marrow. Neutropenia also can result from a shift of neutrophils from the circulating into the marginated cell pools in the circulation. Less commonly, neutropenia results from accelerated destruction of neutrophils or increased egress of neutrophil from the circulation into the tissues. When neutropenia is the sole or dominant abnormality, the condition is called “selective” or “isolated” neutropenia, such as severe congenital neutropenia, chronic idiopathic neutropenia, or drug-induced neutropenia. Neutropenia can occur in other inherited or acquired marrow failure syndromes, such as severe aplastic anemia or Fanconi anemia, in which the condition is a bicytopenia or pancytopenia. In some diseases, several cell lineages are mildly affected, but the reduction in neutrophils is the most severe, such as Felty syndrome. Neutropenia may be an indicator of an underlying systemic disease, such as early cobalamin or transcobalamin deficiency. Neutropenia, particularly severe neutropenia (neutrophil counts <0.5 × 109/L), increases susceptibility to bacterial or fungal infections and impairs the resolution of these infections. Therapy with the hormone primarily responsible for neutrophil production, granulocyte colony-stimulating factor (G-CSF), can increase blood neutrophil counts for most types of neutropenia, although whether its administration makes a clinically useful impact is dependent on the origin, duration, and severity of the neutropenia. There are published clinical guidelines on the rational use of G-CSF to prevent chemotherapy-associated febrile neutropenia.
Neutrophilia is an increase in the absolute neutrophil count to a concentration greater than 2 SDs above the normal population mean value. Demargination of neutrophils or rapid release of neutrophils from the normally large marrow pool transiently increases the blood neutrophil count. Sustained increases require increased production of these cells. Neutrophilia contributes to the inflammatory response and to resolution of infections. Inflammatory and infectious diseases are the most frequent causes of neutrophilia. Bacterial infections usually produce neutrophilia, whereas viral infections may not produce neutrophilia or may raise the neutrophil count only slightly. Solid tumors occasionally engender striking neutrophilia caused by G-CSF production by the malignant cells. Hereditary neutrophilia can be caused by activating mutations within the CSF3R gene. When the neutrophil count is very high (ie, exceeding 50 × 109/L), it is called a leukemoid reaction. Chronic myeloid leukemia and chronic neutrophilic leukemia usually cause sustained neutrophilia.
Acronyms and Abbreviations
ANA, antinuclear antibody; BTH, Bruton tyrosine kinase; G-CSF, granulocyte colony-stimulating factor; GM-CSF, granulocyte-macrophage colony-stimulating factor; Ig, immunoglobulin; IL, interleukin; TRAIL, tumor necrosis factor-related apoptosis-inducing ligand.
Neutropenia refers to an absolute blood neutrophil count (total leukocyte count per microliter × percent of neutrophils) that is less than 2 standard deviations (SDs) below the normal mean of the population.1 In the Danish nationwide health register with approximately 370,000 ...