Drug-induced Hemolytic Anemia

Article1 April 1963Drug-induced Hemolytic AnemiaNANNIE K. M. DE LEEUW, M.D., M.SC., F.A.C.P., LORNE SHAPIRO, M.D., F.R.C.P. (C), F.A.C.P., LOUIS LOWENSTEIN, M.D., F.A.C.P.NANNIE K. M. DE LEEUW, M.D., M.SC., F.A.C.P., LORNE SHAPIRO, M.D., F.R.C.P. (C), F.A.C.P., LOUIS LOWENSTEIN, M.D., F.A.C.P.Author, Article, and Disclosure Informationhttps://doi.org/10.7326/0003-4819-58-4-592 SectionsAboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail ExcerptHemolytic Anemia may result from the administration of oxidant drugs, including primaquine, sulfonamides, nitrofurantoin, acetylsalicylic acid, and acetophenetidine (1-4). Recent publications have emphasized the close etiological relationship of erythrocyte glucose-6-phosphate dehydrogenase (G6PD) deficiency to this type of drug-induced hemolytic anemia (1-6). This deficiency is an inherited, sexlinked trait of incomplete dominance with variable expressivity (7, 8). It is associated with instability of reduced glutathione (GSH) in the red cell, and a slightly decreased red-cell life span (4) which is reduced further, by selective destruction of the older cells, when oxidant drugs are administered. It is believed that this red-cell defect...References1. BEUTLER E: Drug-induced hemolytic anemia (primaquine sensitivity), in The Metabolic Basis of Inherited Disease, ed. by Stanbury, J. B., Wyngaarden, J. B., and Fredrickson, D. S., The McGraw-Hill Book Company, Inc., New York, 1960, chap. 32, p. 1031. Google Scholar2. BEUTLER E: The hemolytic effect of primaquine and related compounds: a review. Blood 14: 103, 1959. CrossrefMedlineGoogle Scholar3. TARLOVBREWERCARSONALVING ARGJPEAS: Primaquine sensitivity. Arch. Intern. Med. (Chicago) 109: 209, 1962. CrossrefMedlineGoogle Scholar4. KELLERMEYERTARLOVBREWER RWARGJ: Hemolytic effect of therapeutic drugs. Clinical considerations of the primaquine-type hemolysis. JAMA 180: 388, 1962. CrossrefMedlineGoogle Scholar5. ALVINGKELLERMEYERTARLOVSCHRIERCARSON ASRWASPE: Biochemical and genetic aspects of primaquine-sensitive hemolytic anemia. Ann. Intern. Med. 49: 240, 1958. LinkGoogle Scholar6. LÖHRWALLER GWHD: Biochemie und Pathogenese der enzymopenischen hämolytischen Anämien. Deutsch. Med. Wschr. 86: 27 & 87, 1961. CrossrefMedlineGoogle Scholar7. SZEINBERGSHEBAADAM ACA: Selective occurrence of glutathione instability in red blood corpuscles of the various Jewish tribes. Blood 13: 1043, 1958. CrossrefMedlineGoogle Scholar8. CHILDSZINKHAMBROWNEKIMBROTORBERT BWHEAELJV: A genetic study of a defect in glutathione metabolism of the erythrocyte. Bull. Hopkins Hosp. 102: 21, 1958. MedlineGoogle Scholar9. HUGULEYERSLEVBERGSAGEL CMAJDE: Drug-related blood dyscrasias. JAMA 177: 23, 1961. CrossrefMedlineGoogle Scholar10. TYSOELOWENSTEIN FWL: Blood volume and hematologic studies in pregnancy and the puerperium. Amer. J. Obstet. Gynec. 60: 1187, 1950. CrossrefMedlineGoogle Scholar11. DACIE JV: Laboratory methods used in the investigation of the haemolytic anaemias, in Practical Haematology, 2d ed., J. & A. Churchill, Ltd., London, 1956, chap. 8, p. 94. Google Scholar12. ZINKHAM WH: An in vitro abnormality of glutathione metabolism in erythrocytes from normal newborns: mechanism and clinical significance. Pediatrics 23: 18, 1959. MedlineGoogle Scholar13. BEUTLER E: The glutathione instability of drug-sensitive red cells: a new method for the in vitro detection of drug sensitivity. J. Lab. Clin. Med. 49: 84, 1957. MedlineGoogle Scholar14. GRAYSTERLING SJK: The tagging of red cells and plasma proteins with radioactive chromium. J. Clin. Invest. 29: 1604, 1950. CrossrefMedlineGoogle Scholar15. ZINKHAMLENHARDCHILDS WHREB: A deficiency of glucose-6-phosphate dehydrogenase activity in erythrocytes from patients with favism. Bull. Hopkins Hosp. 102: 169, 1958. MedlineGoogle Scholar16. CARSONFLANAGANICKESALVING PECLCEAS: Enzymatic deficiency in primaquine-sensitive erythrocytes. Science 124: 484, 1956. CrossrefMedlineGoogle Scholar17. CARSONBREWERICKES PEGJC: Decreased glutathione reductase with susceptibility to hemolysis. J. Lab. Clin. Med. 58: 804, 1961 (abstract). Google Scholar18. OORTLOOSPRINS MJAHK: Hereditary absence of reduced glutathione in the erythrocytes—a new clinical and biochemical entity? Vox Sang. 6: 370, 1961. CrossrefMedlineGoogle Scholar19. MACGIBBONLOUGHRIDGEHOURIHANEBOYD BHLWDODW: Autoimmune haemolytic anaemia with acute renal failure due to phenacetin and p-aminosalicylic acid. Lancet 1: 7, 1960. CrossrefMedlineGoogle Scholar20. MUIRHEADHALDENGROVES EEERM: Drug-dependent Coombs (antiglobulin) test and anemia. Arch. Intern. Med. (Chicago) 101: 87, 1958. CrossrefGoogle Scholar21. SNAPPERMARKSSCHWARTZHOLLANDER IDLL: Hemolytic anemia secondary to Mesantoin. Ann. Intern. Med. 39: 619, 1953. LinkGoogle Scholar22. HARRIS JW: Studies on mechanism of drug-induced hemolytic anemia. J. Lab. Clin. Med. 47: 760, 1956. MedlineGoogle Scholar23. DAUSSETBERGEROT-BLONDEL JY: Etude d'un anticorps allergique actif en présence de para-aminosalicylate de soude (PAS) contre les hématies, les leucocytes et les plaquettes humaines. Vox Sang. 6: 91, 1961. CrossrefMedlineGoogle Scholar24. FREEDMANBARRBRODY ALPSEA: Hemolytic anemia due to quinidine: observations on its mechanism. Amer. J. Med. 20: 806, 1956. CrossrefMedlineGoogle Scholar25. MUIRHEADGROVESGUYHALDENBASS EEMRERRK: Acquired hemolytic anemia, exposures to insecticides and positive Coombs' test dependent on insecticide preparations. Vox Sang. 4: 277, 1959. CrossrefMedlineGoogle Scholar26. STRUMIARAYMOND PVFD: Acquired hemolytic anemia and antipenicillin antibody. Arch. Intern. Med. (Chicago) 109: 603, 1962. CrossrefMedlineGoogle Scholar27. CRUZ WO: Acetylphenylhydrazine anemia. I. The mechanism of erythrocyte destruction and regeneration. Amer. J. Med. Sci. 202: 781, 1941. CrossrefGoogle Scholar28. LOGELANGEMOORE JPRDCV: Characterization of the anemia associated with chronic renal insufficiency. Amer. J. Med. 24: 4, 1958. CrossrefMedlineGoogle Scholar29. DESFORGESDAWSON JFJP: The anemia of renal failure. Arch. Intern. Med. (Chicago) 101: 326, 1958. CrossrefGoogle Scholar30. ROSSPAEGEL JFBL: Acute hemolytic anemia and hemoglobinuria following sulfadiazine medication; report of a case. Blood 1: 189, 1946. CrossrefMedlineGoogle Scholar31. EMERSONHAMCASTLE CPTHWB: Hemolytic action of certain organic oxidants derived from sulfanilamide, phenylhydrazine and hydroquinone. J. Clin, Invest. 20: 451, 1941 (abstract). Google Scholar32. MARKSGROSS PART: Erythrocyte glucose-6-phosphate dehydrogenase deficiency: evidence of differences between Negroes and Caucasians with respect to this genetically determined trait. J. Clin. Invest. 38: 2253, 1959. CrossrefMedlineGoogle Scholar33. THEILBRODINEDOOLAN GBCEPD: Red cell glutathione content and stability in renal insufficiency. J. Lab. Clin. Med. 58: 736, 1961. MedlineGoogle Scholar34. NIKKILÄPITKÄNENVUOPIOFORSELL EAEPO: Erythrocyte enzymes in anemias of different etiology. Ann. Med. Intern. Fenn. 49: 187, 1960. MedlineGoogle Scholar35. HENNEMANALTSCHULEGONCZ DHMDRM: Glutathione in human disease, in Glutathione, Proceedings of Symposium held at Ridgefield, Connecticut, November, 1953, ed. by Colowick, S. P., Kaplan, N. O., and others, Academic Press, New York, 1954, p. 299. CrossrefGoogle Scholar36. MARQUÉZYBACHCAYLA RACJ: Intoxication par la phénylsemicarbazide; anémie hémolytique avec hépatite (2 observations). Arch. Franç. Pédiat. 7: 624, 1950. MedlineGoogle Scholar37. MARIEFABIANISERINGESALETATTALELIACHARMAILLARD JPPJ###: Anémie hémolytique aiguë du nourrisson déterminée par l'administration de phénylsemicarbazide. Ibid. 7: 621, 1950. Google Scholar38. DEBRÉMOZZICONACCIBUHOTGUINAND-DONIOLHERRAULT RPSJA: Anémies hémolytiques aiguës curables de l'enfance. Ibid. 7: 168, 1950. Google Scholar39. OLTRAMARE M: Anémie hémolytique aiguë chez une malade traitée par la Cryogénine et l'Irgafène. Schweiz. Med. Wschr. 83: 156, 1953. MedlineGoogle Scholar40. BARIBEAULONG GLA: Anémie hémolytique secondaire à l'ingestion de Cryogénine. Un. Méd. Canada 90: 1085, 1961. MedlineGoogle Scholar41. KIMBROSACHSTORBERT ELMVJV: Mechanism of the hemolytic anemia induced by nitrofurantoin (Furadantin). Further observations on the incidence and significance of "primaquine-sensitive" red cells. Bull. Hopkins Hosp. 101: 245, 1957. MedlineGoogle Scholar42. ZINKHAMCHILDS WHB: Effect of naphthalene derivatives on glutathione metabolism of erythrocytes from patients with naphthalene hemolytic anemia. J. Clin. Invest. 36: 938, 1957. Google Scholar43. ZINKHAMCHILDS WHB: The effect of vitamin K and naphthalene metabolites on the glutathione metabolism of erythrocytes from normal newborns and patients with naphthalene hemolytic anemia. Amer. J. Dis. Child. 94: 420, 1957 (abstract). Google Scholar44. ZBINDENSTUDER GA: Experimental pathology of iproniazid and related compounds. Ann. NY Acad. Sci. 80: 873, 1959. CrossrefMedlineGoogle Scholar45. KUTCHERLANESEGALL AHDLR: The clinical toxicity of antibiotics and sulfonamides. J. Allergy 25: 135, 1954. CrossrefMedlineGoogle Scholar46. PERRYWINKELMANN HORK: Adverse reactions to sulfamethoxypyridazine (Kynex). Its use in the treatment of dermatitis herpetiformis. JAMA 169: 127, 1959. CrossrefMedlineGoogle Scholar47. SIEGENTHALER W: Die langwirkenden Sulfonamide. Antibiot. Chemother. (Basel) 8: 83, 1960. CrossrefGoogle Scholar48. CARTER RG: Acute hemolytic anemia during sulfonamide therapy. Canad. Med. Ass. J. 84: 112, 1961. MedlineGoogle Scholar49. SPRIGGSSMITHGRIFFITHTRUELOVE AJRSHSC: Heinz-body anaemia due to salicylazosulphapyridine. Lancet 1: 1039, 1958. CrossrefMedlineGoogle Scholar50. DERNBEUTLERALVING RJEAS: The hemolytic effect of primaquine. V. Primaquine sensitivity as a manifestation of a multiple drug sensitivity. J. Lab. Clin. Med. 45: 30, 1955. MedlineGoogle Scholar51. SZEINBERGSHEBAHIRSHORNBODONYI ACNE: Studies on erythrocytes in cases with past history of favism and drug-induced acute hemolytic anemia. Blood 12: 603, 1957. CrossrefMedlineGoogle Scholar52. KELLERMEYERTARLOVSCHRIERALVING RWARSLAS: Hemolytic effect of commonly used drugs on erythrocytes deficient in glucose-6-phosphate dehydrogenase. J. Lab. Clin. Med. 52: 827, 1958 (abstract). Google Scholar53. SZEINBERGASHERSHEBA AYC: Studies on glutathione stability in erythrocytes of cases with past history of favism or sulfa-drug-induced hemolysis. Blood 13: 348, 1958. CrossrefMedlineGoogle Scholar54. NEWTONBASS WAJC: Glutathione-sensitive chronic non-spherocytic hemolytic anemia. Amer. J. Dis. Child. 96: 501, 1958. Google Scholar55. BOGERGAVIN WPJJ: Low-dose long-acting sulfonamides are different. Ann. NY Acad. Sci. 82: 18, 1959. CrossrefMedlineGoogle Scholar56. Editorial. Sulfonamides and the urinary tract. Antibiot. Chemother. (NY) 11: 681, 1961. Google Scholar57. MADSEN ST: Plasma concentrations and renal excretion of long-acting sulfonamides in renal failure. Ibid. 11: 684, 1961. Google Scholar58. KRANTZCARR JCCJ: The sulfonamide drugs and bacterial infections, in The Pharmacological Principles of Medical Practice, 5th ed., The Williams & Wilkins Company, Baltimore, 1961, chap. 9, p. 100. Google Scholar59. NISSENSKADHAUGE NIK: Sulfamethyltiodiazole (Lucosil). Acta Med. Scand. 113: 395, 1943. CrossrefGoogle Scholar60. GOODMANGILMAN LSA: Sulfonamides, in The Pharmacological Basis of Therapeutics, 2nd ed., The Macmillan Company, New York, 1955, chap. 56, p. 1316. Google Scholar61. FERTMANFERTMAN MHMB: Toxic anemias and Heinz bodies. Medicine 34: 131, 1955. CrossrefMedlineGoogle Scholar62. PERRYSCHROEDERCOMENS HMHAP: Abnormalities of circulating cells and proteins in hydralazine-treated patients without toxic symptoms. Amer. J. Med. Sci. 244: 44, 1962. CrossrefMedlineGoogle Scholar63. DUBOISKATZFREEMANGARBAK ELYJVF: Chronic toxicity studies of hydralazine (Apresoline) in dogs, with particular reference to the production of the "hydralazine syndrome." J. Lab. Clin. Med. 50: 119, 1957. MedlineGoogle Scholar64. JANDLENGLEALLEN JHLKDW: Oxidative hemolysis and precipitation of hemoglobin. I. Heinz body anemias as an acceleration of red cell aging. J. Clin. Invest. 39: 1818, 1960. CrossrefMedlineGoogle Scholar65. ALLENJANDL DWJH: Oxidative hemolysis and precipitation of hemoglobin. II. Role of thiols in oxidant drug action. J. Clin. Invest. 40: 454, 1961. CrossrefMedlineGoogle Scholar66. JACOBSJANDL HSJH: Effects of sulfhydryl inhibition on red blood cells. I. Mechanism of hemolysis. J. Clin. Invest. 41: 779, 1962. CrossrefMedlineGoogle Scholar67. JACOBSJANDL HSJH: Effects of sulfhydryl inhibition on red blood cells. II. Studies in vivo. J. Clin. Invest. 41: 1514, 1962. CrossrefMedlineGoogle Scholar This content is PDF only. To continue reading please click on the PDF icon. Author, Article, and Disclosure InformationAffiliations: From the Division of Haematology of the Department of Medicine, Royal Victoria Hospital; and University Clinic, McGill University, Montreal, Canada.Requests for reprints should be addressed to Nannie K. M. de Leeuw, M.D., Royal Victoria Hospital, Montreal 2, Canada. 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DOSSETOR, M.A., B.M., B.CH., PH.D., F.R.C.P.(C)Case 1-1968Beziehung zwischen dem glutathionspiegel und der erythrozytenmenge im blut gesunder menschenThe mechanism of action of local anaestheticsBIOCHEMICAL EFFECTS OF AROMATIC AMINESPapierchromatographische Trennung und quantitative Bestimmungsmethode f�r SH-Glutathion in Blut und GewebenMethemoglobinemia and Heinz Body Hemolytic Anemia Due to Phenazopyridine HydrochlorideDrug-Induced blood dyscrasias 1 April 1963Volume 58, Issue 4Page: 592-607KeywordsDehydrogenasesDrug administrationDrugsGlucose-6-phosphate dehydrogenase deficiencyGlutathioneHematology and oncologyHemolytic anemiaHospital medicinePrimaquineSulfonamide ePublished: 1 December 2008 Issue Published: 1 April 1963 PDF downloadLoading ...