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Neutropenia is present when the neutrophil count is below 1500/mcL, though blacks and other specific population groups may normally have neutrophil counts as low as 1200/mcL The neutropenic patient is increasingly vulnerable to infection by gram-positive and gram-negative bacteria and by fungi The risk of infection is related to the severity of neutropenia Patients with chronic benign neutropenia are free of infection for years despite very low neutrophil levels A variety of bone marrow disorders and nonmarrow conditions may cause neutropenia (Table 13 12) All the causes of aplastic anemia (Table 13 10) and pancytopenia (Table 13 11) may cause neutropenia Isolated neutropenia is often due to an idiosyncratic reaction to a drug, and agranulocytosis (complete absence of neutrophils in the peripheral blood) is almost always due to a drug reaction In these cases, examination of the bone marrow shows an almost complete absence of myeloid precursors, with other cell lines undisturbed Felty s syndrome immune neutropenia associated with seropositive nodular rheumatoid arthritis and splenomegaly is another cause Neutropenia in the presence of a normal bone marrow may be due to immunologic peripheral destruction, sepsis, or hypersplenism Severe neutropenia may be associated with clonal disorders of T
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Table 13 12 Causes of neutropenia
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Bone marrow disorders Aplastic anemia Pure white cell aplasia Congenital (rare) Cyclic neutropenia Drugs: sulfonamides, chlorpromazine, procainamide, penicillin, cephalosporins, cimetidine, methimazole, phenytoin, chlorpropamide, antiretroviral medications Benign chronic Peripheral disorders Hypersplenism Sepsis Immune Felty s syndrome HIV infection Large granular lymphocytosis
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Cullen M et al; Simple Investigation in Neutropenic Individuals of the Frequency of Infection after Chemotherapy +/ Antibiotic in a Number of Tumours (SIGNIFICANT) Trial Group Antibacterial prophylaxis after chemotherapy for solid tumors and lymphomas N Engl J Med 2005 Sep 8;353(10): 988 98 [PMID: 16148284] Walsh TJ et al Caspofungin versus liposomal amphotericin B for empirical antifungal therapy in patients with persistent fever and neutropenia N Engl J Med 2004 Sep 30;351(14): 1391 402 [PMID: 15459300]
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Myeloproliferative disorders are due to acquired clonal abnormalities of the hematopoietic stem cell Since the stem cell gives rise to myeloid, erythroid, and platelet cells, qualitative and quantitative changes are seen in all these cell lines In some disorders (chronic myelogenous leukemia), specific characteristic chromosomal changes are seen In others, no characteristic cytogenetic abnormalities are seen Classically, the myeloproliferative disorders produce characteristic syndromes with well-defined clinical and laboratory features (Tables 13 13 and 13 14) However, these disorders are grouped together because the disease may evolve from one form into another and because hybrid disorders are commonly seen All of the myeloproliferative disorders may progress to acute myelogenous leukemia
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lymphocytes, often with the morphology of large granular lymphocytes
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Clinical Findings
Neutropenia results in stomatitis and in infections due to gram-positive or gram-negative aerobic bacteria or to fungi such as Candida or Aspergillus The most common infections are septicemia, cellulitis, and pneumonia In the presence of severe neutropenia, the usual signs of inflammatory response to infection may be absent Nevertheless, fever in the neutropenic patient should always be assumed to be of infectious origin
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Treatment
Potential causative drugs are discontinued Infections are treated with broad-spectrum antibiotics, but particular attention should be paid to enteric gram-negative bacteria Effective antibiotics include the quinolones such as levofloxacin, 500 mg orally or intravenously daily, or new cephalosporins such as cefepime, 2 g intravenously every 8 hours New antifungal agents such as voriconazole and caspofungin can provide both better efficacy and reduced toxicity compared to amphotericin Many cases of idiopathic or autoimmune neutropenia respond to myeloid growth factors such as granulocyte colony-stimulating factor (G-CSF) Once-weekly or twiceweekly dosage will often be sufficient to produce a protective neutrophil count When Felty s syndrome leads to repeated bacterial infections, splenectomy has been the treatment of choice, but it now appears that sustained use of G-CSF is effective and provides a nonsurgical alternative The prognosis of patients with neutropenia depends on the underlying cause Most patients with drug-induced agranulocytosis can be supported with broad-spectrum antibiotics and will recover completely The myeloid growth factor G-CSF (filgrastim) may be useful in shortening the duration of neutropenia associated with chemotherapy The neutropenia associated with large granular lymphocytes may respond to therapy with either cyclosporine or low-dose methotrexate
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