Summary

Neutrophils are essential components of the haematopoietic and immune system, and quantitative or qualitative abnormalities of neutrophils can result in life-threatening infection. Neutropenia is a low neutrophil count and results from decreased production, accelerated utilisation, increased destruction, or a shift in compartments. A combination of these mechanisms may be present. Causes can be congenital or acquired. The most serious complication of neutropenia is infection, which can be fatal. The source is usually endogenous flora of the gut and mucosa (commonly Staphylococcus and gram-negative organisms). Fungal infections occur with increased frequency, but there is no increased risk of viral or parasitic infection. Common sites of infection include mucous membranes (gingivitis, stomatitis, perirectal abscesses), skin (cellulitis), and lungs (pneumonia). [1] [2]

Classification

There is no standard classification system for neutropenia, but the absolute neutrophil count (ANC) is generally used to grade severity. The ANC is calculated as follows:

ANC = white blood cells (microlitre) x percent (polymorphonuclear cells + bands)/100

An ANC <1500/microlitre or <1.5 x 10^9/L is defined as neutropenia and graded as mild, moderate, or severe: [3]

• Mild: 1000 to 1500/microlitre or 1 to 1.5 x 10^9/L

• Moderate: 500 to 999/microlitre or 0.5 to 0.99 x 10^9/L

• Severe: <500/microlitre or <0.5 x 10^9/L.

As the ANC falls below 1000/microlitre or 1 x 10^9/L, the risk of infection progressively increases. If the ANC falls below 500/microlitre or 0.5 x 10^9/L, infections may be life-threatening. However, there are some diseases, such as autoimmune neutropenia (AIN), in which a low ANC does not confer an infection risk; infections are rare in these patients despite the ANC often being <500/microlitre or <0.5 x 10^9/L.

The ANC varies according to age and ethnicity. It is lower in children than in adults. Children <12 months are not considered neutropenic unless the ANC falls below 1000/microlitre or 1 x 10^9/L. After 10 years of age neutrophil values normally exceed 1500/microlitre or 1.5 x 10^9/L. [4] Black people, Ethiopians, Yemenite Jews, and some Arab populations display lower average values. [5] [6] [7] [8] The normal range in black people has a lower limit of 1400/microlitre or 1.4 x 10^9/L.

Common causes

Infections are the most common causes of neutropenia in adults, followed by drug-induced neutropenias. [9] In Europe the incidence of drug-induced neutropenia in the general population is 1.6 to 9.2 cases per million. The incidence within the US is slightly higher with 2.4 to 15.4 cases per million reported per year. Acquired bone marrow diseases such as the leukemias, lymphomas, and aplastic anaemia are relatively common causes of neutropenia in adults, as are nutritional deficiencies (vitamin B12, folate, copper). Other causes of neutropenia are rare in adults. The epidemiology of pseudoneutropenia (neutrophil maldistribution) is unknown.

In children, the epidemiology is different. Primary autoimmune neutropenia in infancy is the most common cause of neutropenia in children <2 years old. [10] Neonatal alloimmune neutropenia is also a relatively common cause of neutropenia in infants. Infections and medications remain common causes in children. Congenital causes are rarer than acquired causes, and epidemiological data are limited. The most common and important diseases affecting neutrophil production are severe congenital neutropenia and cyclic neutropenia. Common variable immunodeficiency is the most common immunodeficiency encountered.