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Disorders of Granulocytes

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INTRODUCTION

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White blood cells (WBCs), or leukocytes, are 1 of the body’s major defenses in preventing and combating infection. The most common types of leukocytes are granulocytes, lymphocytes, and monocytes. This chapter will deal primarily with granulocytes, which include neutrophils, basophils, and eosinophils. The most common of the granulocytes is the neutrophil. Neutropenia, which is a deficiency of neutrophils, is 1 of the most common hematologic abnormalities during childhood and, when severe, can result in life-threatening infection.

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NEUTROPENIA

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The absolute neutrophil count (ANC) and the relative proportions of neutrophils to lymphocytes vary with age. At birth, neutrophils are the majority and decrease during the first few days of life. During infancy, neutrophils compose approximately 20% to 30% of the circulating WBCs. By 5 years of age, neutrophil and lymphocyte counts are equal, and by puberty, approximately 70% of WBCs are neutrophils.

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Neutropenia is defined by a decrease in the absolute number of circulating mature and band forms of neutrophils, which can be determined by calculating the ANC. The ANC is calculated by multiplying the number of total WBCs obtained from the complete blood count (CBC) by the combined percentage of segmented neutrophils and bands. The normal resting ANC in the general population ranges between 1500 and 8000 cells/mm3 for white children over 6 years of age, while 30% of African American children have an ANC as low as 800 cells/mm3. Based on the ANC, neutropenia can be classified as mild (ANC of 1000–1500 cells/mm3), moderate (ANC of 500–1000 cells/mm3), or severe (ANC < 500 cells/mm3). Neutropenia is associated with an increased chance of developing an infection; however, only patients with severe neutropenia are likely to develop life-threatening infections.

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Patients with neutropenia are most frequently infected with endogenous flora, Gram-negative organisms, Staphylococcus aureus, Staphylococcus epidermidis, streptococci, and enterococci. Susceptibility to bacterial infections varies even in the presence of severe neutropenia. Some patients with chronic neutropenia syndromes with an ANC less than 200 cells do not develop life-threatening infections, while neutropenia induced by immunosuppressive drugs, particularly in conjunction with a malignancy, is associated with higher rates of severe infections, probably due to the additional loss of cellular immunity. Severe neutropenia is associated with skin and soft tissue infections, gingivitis, stomatitis, pneumonia, and septicemia. However, isolated neutropenia is not associated with an increased risk for parasitic, viral, or fungal infections. Acute neutropenia arises when neutrophils are being employed and production is limited. Chronic neutropenia lasting months to years often evolves from impaired production or excessive splenic sequestration. Neutropenia may commonly occur from factors extrinsic to marrow myeloid cells or less frequently as an acquired disorder of myeloid and stem cells. A neutropenia classification schema is shown in Figure 437-1.

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Figure 437-1

A neutropenia classification schema.

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