Chapter 061. Disorders of Granulocytes and Monocytes (Part 6)

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Chapter 061. Disorders of Granulocytes and Monocytes (Part 6) Chapter 061. Disorders of Granulocytes and Monocytes (Part 6) Hereditary Neutropenias Hereditary neutropenias are rare and may manifest in early childhood as aprofound constant neutropenia or agranulocytosis. Congenital forms ofneutropenia include Kostmanns syndrome (neutrophil count myelokathexis (retention of WBCs in the marrow)] syndrome, characterized byneutrophil hypersegmentation and bone marrow myeloid arrest due to mutations inthe chemokine receptor CXCR4; and neutropenias associated with other immunedefects, such as X-linked agammaglobulinemia, Wiskott-Aldrich syndrome, andCD40 ligand deficiency. Mutations in the G-CSF receptor can develop in severecongenital neutropenia and are linked to leukemia. Maternal factors can be associated with neutropenia in the newborn.Transplacental transfer of IgG directed against antigens on fetal neutrophils canresult in peripheral destruction. Drugs (e.g., thiazides) ingested during pregnancycan cause neutropenia in the newborn by either depressed production or peripheraldestruction. In Feltys syndrome—the triad of rheumatoid arthritis, splenomegaly, andneutropenia (Chap. 314)—spleen-produced antibodies can shorten neutrophil lifespan, while LGLs can attack marrow neutrophil precursors. Splenectomy mayincrease neutrophil count in Feltys syndrome and lower serum neutrophil-bindingIgG. Some Feltys syndrome patients also have neutropenia associated with anincreased number of LGLs. Splenomegaly with peripheral trapping anddestruction of neutrophils is also seen in lysosomal storage diseases and in portalhypertension. Neutrophilia Neutrophilia results from increased neutrophil production, increasedmarrow release, or defective margination (Table 61-2). The most important acutecause of neutrophilia is infection. Neutrophilia from acute infection representsboth increased production and increased marrow release. Increased production isalso associated with chronic inflammation and certain myeloproliferative diseases.Increased marrow release and mobilization of the marginated leukocyte pool areinduced by glucocorticoids. Release of epinephrine, as with vigorous exercise,excitement, or stress, will demarginate neutrophils in the spleen and lungs anddouble the neutrophil count in minutes. Cigarette smoking can increase neutrophilcounts into the abnormal range. Leukocytosis with cell counts of 10,000–25,000/µL occurs in response to infection and other forms of acute inflammationand results from both release of the marginated pool and mobilization of marrowreserves. Persistent neutrophilia with cell counts of ≥30,000–50,000/µL is called aleukemoid reaction, a term often used to distinguish this degree of neutrophiliafrom leukemia. In a leukemoid reaction, the circulating neutrophils are usuallymature and not clonally derived. Table 61-2 Causes of Neutrophilia Increased Production Idiopathic Drug-induced—glucocorticoids, G-CSF Infection—bacterial, fungal, sometimes viral Inflammation—thermal injury, tissue necrosis, myocardial and pulmonaryinfarction, hypersensitivity states, collagen vascular diseases Myeloproliferative diseases—myelocytic leukemia, myeloid metaplasia,polycythemia vera Increased Marrow Release Glucocorticoids Acute infection (endotoxin) Inflammation—thermal injury Decreased or Defective Margination Drugs—epinephrine, glucocorticoids, nonsteroidal anti-inflammatoryagents Stress, excitement, vigorous exercise Leukocyte adhesion deficiency type 1 (integrin βchain, CD18); leukocyteadhesion deficiency type 2 (selectin ligand, CD15s, sialyl-Lewisx)