Induced Agranulocytosis

Corzo, D., et al., "The Major Histocompatibility Complex Region Marked by HSP and HSP70-2 Variant is Associated with Clozapine-induced Agranulocytosis in Two Different Ethnic Groups," Blood, 86, 3835-3840 (1995). 

Guffy, M.M., Goeken, N.E., and Burns, C.P., Granulocytotoxic antibodies in a patient with propylthiouracil-induced agranulocytosis, Arch. Intern. Med., 144, 1687, 1984. 

Uetrecht JP, Ma HM, MacKnight E, et al. Oxidation of aminopyrine by hypochlorite to a reactive dication possible implications for aminopyrine-induced agranulocytosis. Chem Res Toxicol 1995 8(2) 226-233. 

Uetrecht JP, Zahid N, Whitfield D. Metabolism of vesnarinone by activated neutrophils implications for vesnarinone-induced agranulocytosis. J Pharmacol Exp Ther 1994 270(3) 865-872. 

Liu ZC, Uetrecht JP. Metabolism of ticlopidine by activated neutrophils implications for ticlopidine-induced agranulocytosis. Drug Metab Dispos 2000 28(7) 726-730. 

WadeUus, M., Stjemberg, E., Wiholm, B. E., and Rane, A. (2000) Polymorphisms of NAT2 in relation to sulphasalazine-induced agranulocytosis. Pharmacogenetics. 10, 35-41. 

Clozapine Myeloproliferative disorders uncontrolled epilepsy history of clozapine-induced agranulocytosis or severe granulocytopenia should not be used with other agents having a well-known potential to cause agranulocytosis or suppress bone marrow function. 

Mosyagin, L, Dettling, M., Roots, L, Mueller-Oerlinghausen, B. and Cascorbi, I. (2004) Impact of myeloperoxidase and NADPH-oxidase polymorphisms in drug-induced agranulocytosis. Journal of Clinical Psychopharmacology, 24, 613-617. 

Garbe, E. (2007) Non-chemotherapy drug-induced agranulocytosis. Expert Opinion on Drug Safety, 6, 323-335. 

Idiosyncratic drug-induced agranulocytosis update of an old disorder. European Journal of Internal Medicine, 17, 529-535. 

Alvir JM, Lieberman JA, Safferman AZ, et al Clozapine-induced agranulocytosis incidence and risk factors in the United States. N Engl J Med... 

Barnas C, Zwierzina H, Hummer M, et al Granulocyte-macrophage colony-stimulating factor (GM-CSF) treatment of clozapine-induced agranulocytosis a case report. J Clin Psychiatry 53 245-247, 1992... 

Nielsen H Recombinant human granulocyte colony-stimulating factor (rhG-CSF filgrastim) treatment of clozapine-induced agranulocytosis. J Intern Med 234 529-531, 1993... 

G. Other applications Neupogen may also be useful in preventing opportunistic diseases in patients infected with the human immunodehciency virus and for drug-induced agranulocytosis. The use of topical hlgrastim may be effective in reducing oral mucositis due to intensive chemotherapy. 

Initially, the mortality rate from clozapine-induced agranulocytosis was about 40%, but it has decreased by more than half. Now, while the mortality rate of agranulocytosis complicated by infection is still 40%, without infection, it is approximately 15%. In U.S. clinical trials, the incidence is about one per 100, but because this outcome is based on only 1,000 patients, it may not be an accurate estimate. It is notable that some who developed clozapine-induced agranulocytosis were later able to tolerate other antipsychotics without a recurrence, again implying a different underlying mechanism. 

Gerson SL, Gullion G, Yeh H-S, et al. Granulocyte colony-stimulating factor for clozapine-induced agranulocytosis. Lancet 1992 340 1097. 

Skin reactions occur early in therapy but can subside with continued treatment. Jaundice, which can also occur early, is of the cholestatic type, similar to that attributed to chlorpromazine. Agranulocytosis is a rare complication, as are cases of leukocytosis, leukopenia, and eosinophilia. There are no data on the incidence of antidepressant-induced agranulocytosis, except to note that it is rare with all of the agents discussed in this chapter. 

Various combinations of mood stabilizers and antipsychotics may then be considered, always in a stepwise strategy. Although clozapine may be combined with lithium and/or VPA, we caution against the combined use of clozapine plus CBZ, given the former s propensity to induce agranulocytosis and the latter s ability to suppress bone marrow production. 

Antiarrhythmic therapy carries with it a number of risks. In some cases, the risk of an adverse reaction is clearly related to high dosages or plasma concentrations. Examples include lidocaine-induced tremor or quinidine-induced cinchonism. In other cases, adverse reactions are unrelated to high plasma concentrations (eg, procainamide-induced agranulocytosis). For many serious adverse reactions to antiarrhythmic drugs, the combination of drug therapy and the underlying heart disease appears important. 

Outcomes have been reported in a consecutive series of 91 patients hospitalized with non-chemotherapy drug-induced agranulocytosis from 1985-2000 (34). All but two survived. Antithyroid drugs were the cause of agranulocytosis in 20% of cases. Univariate and multivariate analyses failed to reveal a specific effect of antithyroid drugs on the time to neutrophil recovery. In contrast, hemopoietic growth factor treatment was associated with speedier hematological recovery. 

There have been anecdotal reports of the use of G-CSF in cases of thionamide-induced agranulocytosis (45). In a retrospective review (46) the outcomes in 10 severe... 

Antithyroid drug-induced agranulocytosis. The usefulness of routine white blood cell count monitoring. Arch Intern... 

Tajiri J, Noguchi S. Antithyroid drug-induced agranulocytosis special reference to normal white blood cell count agranulocytosis. Thyroid 2004 14(6) 459-62. 

Tamai H, Sudo T, Kimura A, Mukuta T, Matsubayashi S, Kuma K, Nagataki S, Sasazuki T. Association between the DRB1 08032 histocompatibility antigen and methimazole-induced agranulocytosis in Japanese patients with Graves disease. Ann Intern Med 1996 124(5) 490-4. 

Maloisel F, Andres E, Kaltenbach G, Noel E, Koumarianou A. Prognostic factors of hematologic recovery in nonchemotherapy drug-induced agranulocytosis. Haematologica 2003 88 470-1. 

Hirsch D, Luboshitz J, Blum I. Treatment of antithyroid drug-induced agranulocytosis by granulocyte colony-stimulating factor a case of primum non nocere. Thyroid 1999 9(10) 1033-5. 

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