Chapter 65: Neutropenia and Neutrophilia

SUMMARY

Neutropenia designates a blood absolute neutrophil count that is less than 2 SD 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 neutrophil is the most severe, such as Felty syndrome. Neutropenia may be an indicator of an underlying systemic disease, such as early vitamin B₁₂ or transcobalamin deficiency. Neutropenia, particularly severe neutropenia (neutrophil counts <0.5 × 10⁹/L [500/μL]), 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, 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. Clinical guidelines have been published on the rational use of the drug.

Neutrophilia is an increase in the absolute neutrophil count to a concentration greater than 2 SD above the normal population mean value. 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. Hereditary neutrophilia can be caused by activating mutations within the CSF3R gene. When the neutrophil count is very high, it may be referred to as a leukemoid reaction. The rare neutrophilic variants of chronic myeloid leukemia and chronic neutrophilic leukemia may result in striking neutrophilia. Demargination of neutrophils or rapid release of neutrophils from a large marrow pool may transiently increase the blood neutrophil count. Sustained increased require increased production of these cells.

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.