Neutropaenia

Introduction

Neutropaenia is defined as a decrease in the number of circulating neutrophils. The neutrophil count varies with age, sex and racial grouping. The severity of neutropaenia is usually graded as follows:

• Mild: neutrophil count 1.0 to 1.5 × 10 ⁹ /L

• Moderate: neutrophil count 0.5 to 1.0 × 10 ⁹ /L

• Severe: neutrophil count <0.5 × 10 ⁹ /L.

The risk of infection rises as the neutrophil count falls; it becomes significant once the neutrophil count drops below 1.0 × 10 ⁹ /L. Australian guidelines have defined febrile neutropaenia as existing in a patient with a temperature above 38.4°C (or above 38°C on two occasions) with a neutrophil count less than 0.5 × 10 ⁹ /L or less than 1.0 × 10 ⁹ /L and likely to fall to less than 0.5 × 10 ⁹ /L. These patients must be examined for signs of systemic compromise ( Box 13.2.1 ).

Neutropaenic patients are at greater risk of overwhelming infection if the onset of the neutropaenia is acute rather than chronic and, in the case of patients receiving cancer chemotherapy, if the absolute neutrophil count is in the process of falling rather than rising.

Signs or symptoms of infection in the presence of severe neutropaenia, especially with features of systemic compromise, constitute a true emergency that mandates rapid assessment and aggressive management to prevent progression to overwhelming sepsis. In the emergency department (ED) setting, this is most commonly encountered when a patient presents with fever in the context of chemotherapy for cancer.

Pathophysiology and aetiology

Polymorphonuclear neutrophils are formed in marrow from the myelogenous cell series. Pluripotent haematopoietic stem cells are committed to a particular cell lineage through the formation of colony forming units, which further differentiate to form given white cell precursors. The mature neutrophil has a multi-lobed nucleus and granules in the cytoplasm. The cells are termed ‘neutrophilic’ because of the lilac colour of the granules caused by the uptake of both acidic and basic dyes.

The neutrophils leave the marrow and enter the circulation, where they have a life span of only 6 to 10 hours before entering the tissues. Here they migrate by chemotaxis to sites of infection and injury, where they phagocytose and destroy foreign material. In health, about half of the available mature neutrophils are in the circulation. ‘Marginal’ cells are adherent to vascular endothelium or in the tissues and are not measured by the full blood count. Some individuals have fixed increased marginal neutrophil pools and decreased circulating pools; they are said to have benign idiopathic neutropaenia.

For a previously normal individual to become neutropaenic, there must be decreased production of neutrophils in the marrow, decreased survival of mature neutrophils or a redistribution of neutrophils from the circulating pool. The important causes are shown in Box 13.2.2 .