Caron A. Jacobson

Nancy Berliner


The normal range for the peripheral white blood count (WBC) is between 4.5 × 109/L and 10.0 × 109/L, with a mean of 7.5 × 109/L. The total WBC includes neutrophils and lymphocytes, as well as smaller numbers of monocytes, basophils, and eosinophils. Leukopenia, a depressed WBC, may reflect either neutropenia or lymphopenia. Neutrophils constitute about 60% of the peripheral WBC, and therefore, reduction of WBC number most commonly reflects a decreased absolute neutrophil count (ANC). Neutropenia can occur as a secondary manifestation of an underlying disease or exposure or may reflect primary hematologic disease. This chapter focuses on the primary and secondary causes of neutropenia.


The circulating neutrophil pool represents only approximately 5% of the body’s total neutrophil number. It is therefore a fairly distant reflection of the dynamics of neutrophil maturation within the bone marrow.1 Neutrophils arise in the bone marrow from a multipotent progenitor cell that also gives rise to all other formed elements of the blood. Maturation of neutrophil precursors occurs over 6 to 10 days. The majority of mature neutrophils constitute a storage pool that remains in the bone marrow poised for release as needed. The proliferating pool and storage pool together make up about 95% of the total granulocyte mass. Of the remaining 5% of neutrophils that enter the peripheral circulation, about 60% are a “marginating pool” that adheres to the vascular endothelium. These marginated neutrophils are easily mobilized into the circulation in response to stress. Circulating neutrophils survive for only 6 to 12 hours; when mobilized to sites of infection or inflammation, they can migrate into tissues where they survive for 1 to 4 days. Neutropenia can occur upon disruption of any of these processes: it may reflect decreased marrow production, increased margination (especially in the setting of splenomegaly and sequestration by the spleen), or peripheral immune destruction of mature cells.


Neutropenia is defined by a decreased ANC, calculated by multiplying the total WBC by the percentage of neutrophils and bands noted on the differential cell count. What constitutes a low ANC differs by age, sex, race, and other factors; the normal range for the ANC for a given population, then, is defined as the mean ANC for that population +/- two standard deviations.2, 3 In general, however, an ANC less than 1.5 × 109/L is considered neutropenic in most patient populations. Neutropenia can be further classified as mild, moderate, or severe based on the degree of ANC depression: an ANC of 1.0 to 1.5 × 109/L is considered mild, 0.5 to 1.0 × 109/L is considered moderate, and less than 0.5 × 109/L is considered severe. Although this classification is useful in predicting the risk of severe bacterial infection, other features may modify the risk. The risk of infection may be modified by the neutrophil storage pool.4 Risk may also be modified by the cause of neutropenia. For instance, chemotherapyinduced neutropenia is associated with a much greater risk of serious infection than chronic immune or nonimmune neutropenia. The risk of infection is also a function of both the degree and duration of neutropenia.5

Oct 21, 2016 | Posted by in HEMATOLOGY | Comments Off on Neutropenia

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