Chapter 30: Neutropenia and Neutrophilia

NEUTROPENIA

• Leukopenia refers to a reduced total leukocyte count.

• Granulocytopenia refers to a reduced granulocyte (neutrophils, eosinophils, and basophils) count.

• Neutropenia refers to a reduced neutrophil count: less than 1.5 × 10⁹/L in patients from age 1 month to 10 years and less than 1.8 × 10⁹/L in patients older than age 10 years. (Table 29–1 outlines the classification of neutrophil disorders.)

• Agranulocytosis literally means a complete absence of blood granulocytes but is used to indicate very severe neutropenia, usually a neutrophil count less than 0.5 × 10⁹/L.

• Americans of African descent (as do some other ethnic groups) have lower normal mean neutrophil counts than do Americans of European descent.

• The risk of infections is inversely related to the severity of the neutropenia: patients with qualitatively normal neutrophils and neutrophil counts of 1.0 to 1.8 × 10⁹/L are at little risk, patients with counts of 0.5 to 1.0 × 10⁹/L are at low or slight risk, and patients with counts less than 0.5 × 10⁹/L are at higher risk.

• Patients with severe, prolonged neutropenia are at particular risk for bacterial and fungal infections.

• The risk is calculated not only by the neutrophil count but by complicating factors as follows:

  — The longer the duration of severe neutropenia, the greater the risk of infection.

  — The risk of infection is greater when the count is falling rapidly or when there is associated monocytopenia, lymphocytopenia, or hypogammaglobulinemia.

  — Neutropenia caused by disorders of hematopoietic progenitor cells (eg, chemotherapy-induced marrow suppression, severe inherited neutropenia) generally results in a greater susceptibility to infections compared with neutropenia resulting from accelerated turnover (eg, immune neutropenia).

  — Integrity of the skin and mucous membranes, blood supply to tissues, presence of an indwelling catheter, and nutritional status are also important in considering infection risk.

• Neutropenia can be classified as: (1) disorders of neutrophil production, (2) disorders of neutrophil distribution and turnover, (3) drug-induced neutropenia, and (4) neutropenia with infectious diseases.

DISORDERS OF PRODUCTION

Inherited Neutropenia Syndromes

Kostmann Syndrome

• Inheritance can be an autosomal dominant (mutation in gene for neutrophil elastase, ELA-2), recessive (mutation in gene encoding mitochondrial protein, HAX-1), or sporadic (mutation in ELA-2). Mutation in the gene for the glucose-6-phosphate catalytic subunit (G6PC3) also can cause severe neutropenia.

• Mutations in the receptor for granulocyte colony-stimulating factor (G-CSF) and in RAS may be present and, although not the cause of the neutropenia, may predispose to evolution to acute myelogenous leukemia.

• Otitis, gingivitis, pneumonia, enteritis, peritonitis, and bacteremia usually occur in the first month of life.

• Neutrophil count is often less than 0.2 × 10⁹/L. Eosinophilia, monocytosis, and mild splenomegaly may be present.

• Marrow usually shows some early neutrophil precursors but few myelocytes or mature neutrophils.

• Immunoglobulin levels are usually normal or increased ...