Neutropenia drug-induced

The last potential mechanism to be discussed in this chapter is drug-induced altered receptor expression. Hematopoiesis is a very intricate process that is regulated by cytokines and cell-cell interactions. Interruption with any of these processes can result in hematotoxicity. For example, zidovudine (AZT) decreases Epo [27], GM-CSFaand to lesser extent IL-3 receptor expression [7]. Decrease in the expression of the above receptors seems to lead to anemia and neutropenia, by decreasing the number of CFU-E and CFU-GM, respectively. 

T. and Alt, M. (2008) Recognition and management of drug-induced blood cytopenias the example of drug-induced acute neutropenia and agranulocytosis. Expert Opinion on Drug Safety, 1, 481-489. 

Approximately 30% of patients using sulfasalazine discontinue the drug because of toxicity. Common adverse effects include nausea, vomiting, headache, and rash. Hemolytic anemia and methemoglobinemia also occur, but rarely. Neutropenia occurs in 1-5% of patients, while thrombocytopenia is very rare. Pulmonary toxicity and positive double-stranded DNA are occasionally seen, but drug-induced lupus is rare. Reversible infertility occurs in men, but sulfasalazine does not affect fertility in women. The drug does not appear to be teratogenic. 

Akamizu T, Ozaki S, Hiratani H, Uesugi H, Sobajima J, Hataya Y, Kanamoto N, Saijo M, Hattori Y, Moriyama K, Ohmori K, Nakao K. Drug-induced neutropenia associated with anti-neutrophil cytoplasmic antibodies (ANCA) possible involvement of complement in granulocyte cytotoxicity. Clin Exp Immunol 2002 127(l) 92-8. 

Arneborn P, Palmblad J. Drug-induced neutropenia—a survey for Stockholm 1973-1978. Acta Med Scand 1982 212(5) 289-92. 

In a study using the UK General Practice Research Database to determine rates of drug-induced, rare, serious adverse effects on the liver, kidneys, skin, or blood, occurring within 45 days of completing a prescription or refill in 54 803 users of either fluconazole or itraconazole, three had illnesses for which a fluconazole-induced cause could not be ruled out one with thrombocytopenia, one with neutropenia, and one with an abnormal liver function test just after receiving fluconazole (31). The rates were 2.8/100 000 prescriptions (95% Cl = 0.8, 10) for serious, adverse blood events and 1.4/100 000 prescriptions (95% Cl = 0.25, 8.2) for serious, adverse liver events. These results suggest that fluconazole does not commonly have serious adverse effects on the liver, kidneys, skin, or blood. 

A hemodialysis patient developed refractory pleural effusion with prolonged leukopenia and thrombocytopenia, and another developed sudden cyanotic dyspnea with subsequent death after G-CSF administration for drug-induced neutropenia (93). The authors suggested that hemodialysis patients receiving G-CSF may have an increased risk of adverse effects. 

A 300 mg dose of rifabutin is usually well tolerated. Adverse effects include neutropenia, thrombocytopenia, rash, and gastrointestinal disturbances (nausea, flatulence). Myositis (12) and uveitis (13) are rarely observed. The drug-induced lupus-like syndrome has been linked in a few cases with rifampicin and rifabutin. 

Weitzman SA, Stossel TP. Drug-induced immunological neutropenia. Lancet 1978 l(8073) 1068-72. 

Koo KB, Bachand RL, Chow AW. Vancomycin-induced neutropenia. Drug Intell Clin Pharm 1986 20(10) 780-2. 

Pessina A, Albella B, Bayo M, et al. Application of the CFU-GM assay to predict acute drug-induced neutropenia An international blind trial to validate a prediction model for the maximum tolerated dose (MTD) of myelosuppressive xenobiotics. Toxicol Sci. 2003,-75(2) 355-367. 

Reduced immunity due to drug-induced neutropenia or cell-mediated immunity. Potent inhibition of gastric acid by proton pump inhibitors (PPI) can facilitate growth of Candida PPI also may inhibit cytotoxic effect of lymphocytes and reduce salivary secretion. 

Myelosuppressant chemotherapy, in bone marrow transplantation, to reduce length of drug-induced neutropenia (aplastic anemia, hairy cell leukemia, AIDS)... 

As with drug-induced hemolytic anemia and thrombocytopenia, affected patients will usually have taken the responsible drug for at least 1 or 2 weeks before presenting with symptoms such as sore throat, pneumonia, and sometimes overwhelming sepsis. Profound neutropenia is found in the blood, but platelet levels and hematocrit are usually normal. Identifiable neutrophil precursors may be completely absent from the marrow or may be arrested in development, whereas cells of the megakaryocyte and erythroid lineages are normal. 

Adachi JD, Bensen WG, Kassam Y el al (1987) Gold induced thrombocytopenia 12 cases and a review of the literature. Semin Arthritis Rheum 16 287-293 Andersohn F, Konzen C, Garbe E (2007) Non-chemotherapy dmg-induced agranulocytosis a systematic review of case reports. Ann Intern Med 146 657-665 Andres E, Maloisel F (2008) Idiosyncratic drug-induced agranulocytosis ot acute neutropenia. Curr Opin Hematol 15 15-21... 

Many autoimmune diseases, such as hemolytic anemia, glomerular nephritis, and neutropenia, are induced by certain metals, pesticides, and a number of drugs. In such automimmune disorders, the immune system produces autoantibodies to endogenous antigens, causing damage to normal tissues. 

Immunologic A 47-year-old woman developed a drug-induced hypersensitivity syndrome, rarely associated with teicoplanin, after receiving teicoplanin for 10 days [48 ]. She developed fever, lymphadenopa-thy, myalgia, raised aminotransferases and CRP, and mild neutropenia and thrombocytopenia all resolved within 7 days of drug withdrawal. She had previously developed a neutropenia after receiving vancomycin. 

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