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Aprindine-Induced Agranulocytosis: Evidence for Immunologic Mechanism

Aprindine-Induced Agranulocytosis: Evidence for Immunologic Mechanism Abstract • Clinical use of aprindine hydrochloride is occasionally complicated by agranulocytosis. The mechanisms that underlie this disorder are not well understood. Agranulocytosis developed in a 76-year-old woman one month after treatment with aprindine was begun. Her bone marrow was infiltrated with confluent lymphocyte and plasma cell nodules. Although her serum showed no leukoagglutinins, it was found to kill her own leukocytes in the presence of complement, as shown by suppression of postphagocytosis respiratory burst. When complement was omitted or when her serum was treated with anti-IgM, the cytotoxicity was partially suppressed. Treatment of serum with anti-IgG had no such effect. Cytotoxicity disappeared in 28 days, concomitant with return of polymorphonuclear neutrophil leukocytes. These findings offer evidence that aprindine neither potentiated nor suppressed cytotoxicity. Therefore, this drug is believed to stimulate development of an immunogenic clone that produces antileukocyte antibodies. (Arch Intern Med 1983;143:241-243) References 1. Van Leeuwen R, Meyboom RH: Agranulocytosis and aprindine. Lancet 1976;2:1137.Crossref 2. Hausamen TV, Weber FW: Todlich verlaufene agranulozytose unter antiarrhythmischer therapie mit aprindin. Dtsch Med Wochenschr 1977;42: 1523-1524. 3. Bodenheimer HC Jr, Samarel AM: Agranulocytosis associated with aprindine therapy. Arch Intern Med 1979;139:1181-1182.Crossref 4. Opie LH: Aprindine and agranulocytosis. Lancet 1980;2:689-690.Crossref 5. Zipes DP, Troup PJ: New antiarrhythmic agents: Amiodarome, aprindine, disopyramide, ethmozin, mexiletine, tocaimide, verapamil. Am J Cardiol 1978;41:1005-1024.Crossref 6. Danilo P Jr: Aprindine. Am Heart J 1979;97:119-124.Crossref 7. McIntyre PA, Laleli YR, Hodkinson BA, et al: Evidence for antileukocytic antibodies as a mechanism for drug-induced agranulocytosis. Trans Assoc Am Physicians 1971;84:217-225. 8. Pisciotta AV: Immune and toxic mechanisms in drug-induced agranulocytosis. Semin Hematol 1973;10:279-310. 9. Pisciotta AV, Ebbe S, Lennon EJ, et al: Following administration of phenothiazine derivatives. Am J Med 1958;25:210-223.Crossref 10. Pisciotta AV, Santos AS: Studies on agranulocytosis: VI. The effect of clinical treatment with chlorpromazine on nucleic acid synthesis of granulocyte precursors in normal persons. J Lab Clin Med 1965;65:228-239. 11. Pisciotta AV: Studies on agranulocytosis: IX. A biochemical defect in chlorpromazine sensitive marrow cells. J Lab Clin Med 1971;78:435-448. 12. Thompson JS, Herbick JM, Klassen LW, et al: Studies on levamisole induced agranulocytosis. Blood 1980;56:388-396. http://www.deepdyve.com/assets/images/DeepDyve-Logo-lg.png Archives of Internal Medicine American Medical Association

Aprindine-Induced Agranulocytosis: Evidence for Immunologic Mechanism

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Publisher
American Medical Association
Copyright
Copyright © 1983 American Medical Association. All Rights Reserved.
ISSN
0003-9926
eISSN
1538-3679
DOI
10.1001/archinte.1983.00350020063013
Publisher site
See Article on Publisher Site

Abstract

Abstract • Clinical use of aprindine hydrochloride is occasionally complicated by agranulocytosis. The mechanisms that underlie this disorder are not well understood. Agranulocytosis developed in a 76-year-old woman one month after treatment with aprindine was begun. Her bone marrow was infiltrated with confluent lymphocyte and plasma cell nodules. Although her serum showed no leukoagglutinins, it was found to kill her own leukocytes in the presence of complement, as shown by suppression of postphagocytosis respiratory burst. When complement was omitted or when her serum was treated with anti-IgM, the cytotoxicity was partially suppressed. Treatment of serum with anti-IgG had no such effect. Cytotoxicity disappeared in 28 days, concomitant with return of polymorphonuclear neutrophil leukocytes. These findings offer evidence that aprindine neither potentiated nor suppressed cytotoxicity. Therefore, this drug is believed to stimulate development of an immunogenic clone that produces antileukocyte antibodies. (Arch Intern Med 1983;143:241-243) References 1. Van Leeuwen R, Meyboom RH: Agranulocytosis and aprindine. Lancet 1976;2:1137.Crossref 2. Hausamen TV, Weber FW: Todlich verlaufene agranulozytose unter antiarrhythmischer therapie mit aprindin. Dtsch Med Wochenschr 1977;42: 1523-1524. 3. Bodenheimer HC Jr, Samarel AM: Agranulocytosis associated with aprindine therapy. Arch Intern Med 1979;139:1181-1182.Crossref 4. Opie LH: Aprindine and agranulocytosis. Lancet 1980;2:689-690.Crossref 5. Zipes DP, Troup PJ: New antiarrhythmic agents: Amiodarome, aprindine, disopyramide, ethmozin, mexiletine, tocaimide, verapamil. Am J Cardiol 1978;41:1005-1024.Crossref 6. Danilo P Jr: Aprindine. Am Heart J 1979;97:119-124.Crossref 7. McIntyre PA, Laleli YR, Hodkinson BA, et al: Evidence for antileukocytic antibodies as a mechanism for drug-induced agranulocytosis. Trans Assoc Am Physicians 1971;84:217-225. 8. Pisciotta AV: Immune and toxic mechanisms in drug-induced agranulocytosis. Semin Hematol 1973;10:279-310. 9. Pisciotta AV, Ebbe S, Lennon EJ, et al: Following administration of phenothiazine derivatives. Am J Med 1958;25:210-223.Crossref 10. Pisciotta AV, Santos AS: Studies on agranulocytosis: VI. The effect of clinical treatment with chlorpromazine on nucleic acid synthesis of granulocyte precursors in normal persons. J Lab Clin Med 1965;65:228-239. 11. Pisciotta AV: Studies on agranulocytosis: IX. A biochemical defect in chlorpromazine sensitive marrow cells. J Lab Clin Med 1971;78:435-448. 12. Thompson JS, Herbick JM, Klassen LW, et al: Studies on levamisole induced agranulocytosis. Blood 1980;56:388-396.

Journal

Archives of Internal MedicineAmerican Medical Association

Published: Feb 1, 1983

References