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BACKGROUND

NEUTROPENIA

Neutrophils are the cellular elements of the blood, which provide a large portion of anti-bacterial immunity to the body. The risk of sepsis, fungal infections, and mucositis correlates with the severity of neutropenia.1 Neutrophils phagocytize bacteria opsonized by either immunoglobulin or complement and kill them by means of enzymatic and oxidative mechanisms. Because neutrophils play such an important role in the killing of bacteria and fungi, neutropenic patients may succumb to severe infections caused by either. Immunity is preserved until neutrophil counts are profoundly suppressed. As with red blood cells or platelets, the absolute number of circulating neutrophils is determined by rate of production in the marrow as well as circulating half-life. Therefore absolute neutrophil count (ANC) will be influenced by processes that affect production or maturation of neutrophils in the marrow as well as conditions that shorten neutrophil survival in the periphery. Since the life span of a circulating neutrophil is on the order of hours rather than days, ANC can be an early indication of hematopoietic activity in the marrow compartment. However, there are actually two distinct populations of neutrophils in the circulation—one free in the blood and the other associated with the endothelial surface of blood vessels. Glucocorticoid steroids such as prednisone or dexamethasone have a demarginating effect on neutrophils, resulting in higher ANCs in blood samples, especially in the first hours-to-days of taking such medications. Therefore neutrophil counts can be influenced by the rate of demargination of endothelial-associated cells into the circulation.

Normal neutrophil levels vary between individuals of different races and ages; however, an ANC below 1000 cells/μL represents neutropenia. ANC, determined by total white blood cell count in the CBC as well as the percentage of cells of the neutrophilic lineage in the differential, is calculated as follows:

ANC = WBC × (% segmented neutrophils + % band or earlier myeloid forms)/100.

 

Thus the ANC for a person whose CBC shows a WBC of 10,000 cells/μL and a differential of 50% neutrophils, 30% lymphocytes, 10% monocytes, and 10% band forms would calculate to 6000 cells/μL. Conventionally, neutropenia is classified by the absolute number of circulating neutrophils (ANC) and is usually classified as: mild (1000–1500 cells/μL), moderate (500–1000 cells/μL), severe (<500 cells/μL), or very severe (<200 cells/μL). Generally, neutrophil counts below 1000 are abnormal and warrant further investigation.

ISOLATED NEUTROPENIA

Neutropenia, whether isolated or as part of a broader clinical scenario, may be caused by a number of different underlying conditions (Table 90-1). The epidemiology, presenting symptoms, risk of infection, clinical course, and management differ depending on the etiology. The diagnostic approach to the neutropenic patient depends on clinical context and should be guided by whether neutropenia is accompanied by other hematologic imbalances (Table 90-2). “Isolated neutropenia” implies that every other aspect of the CBC (differential, hemoglobin/hematocrit, mean corpuscular volume [MCV], and platelet count) is normal for age. Congenital forms such as Kostmann disease, cyclic neutropenia, and ...

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