Seminars in Hematology
Volume 42, Issue 3 , Pages 137-144 , July 2005

The Changing Spectrum of Drug-Induced Immune Hemolytic Anemia

  • Patricia A. Arndt

      Affiliations

    • Corresponding Author InformationAddress correspondence to Patricia A. Arndt, MS, MT(ASCP)SBB, Research Department, American Red Cross Blood Services, 100 Red Cross Cir, Pomona, CA 91768.
  • ,
  • George Garratty

References 

  1. Petz LD , Garratty G . In: Immune Hemolytic Anemias . (ed 2). Philadelphia, PA: Churchill Livingstone; 2004;
  2. Snapper I , Marks D , Schwartz L , Hollander L . Hemolytic anemia secondary to mesantoin . Ann Intern Med . 1953;39:619–623
  3. Worlledge SM . Immune drug-induced haemolytic anaemias . Semin Hematol . 1969;6:181–200
  4. Petz LD , Garratty G . In: Acquired Immune Hemolytic Anemias . (ed 1). New York, NY: Churchill Livingstone; 1980;
  5. Garratty G . Review (Drug-induced immune hemolytic anemia—The last decade) . Immunohematology . 2004;20:138–146
  6. Garratty G , Arndt PA , Leger RM . The changing spectrum of drug-induced immune hemolytic anemia over the last 25 years . Blood . 2003;102:560a; (abstr)
  7. Dameshek W . Alpha-methyldopa red-cell antibody (Cross-reaction or forbidden clones) . N Engl J Med . 1967;276: 1382-?
  8. Kirtland HH , Mohler DN , Horwitz DA . Methyldopa inhibition of suppressor-lymphocyte function (A proposed cause of autoimmune hemolytic anemia) . N Engl J Med . 1980;302:825–832
  9. Garratty G , Arndt P , Prince HP , Shulman I . The effect of methyldopa and procainamide on suppressor cell activity . Br J Haematol . 1992;84:310–315
  10. Miescher P , Straessle R . Experimentelle studien über den mechanismua der thrombocyten-schädigung durch antigen-antikörperreaktionen . Vox Sang . 1956;1:83
  11. Miescher PA , Cooper N . The fixation of soluble antigen-antibody-complexes upon thrombocytes . Vox Sang . 1960;5:138–142
  12. Shulman NR . Immunoreactions involving platelets. I. A steric and kinetic model for formation of a complex from a human antibody, quinidine as a haptene, and platelets; and for fixation of complement by the complex . J Exp Med . 1958;107:665–690
  13. Shulman NR . A mechanism of cell destruction in individuals sensitized to foreign antigens and its implications in auto-immunity. Combined clinical staff conference at the National Institutes of Health . Ann Intern Med . 1964;60:506–521
  14. Habibi B . Drug induced red blood cell autoantibodies co-developed with drug specific antibodies causing haemolytic anaemias . Br J Haematol . 1985;61:139–143
  15. Mueller-Eckhardt C , Salama A . Drug-induced immune cytopenias (A unifying pathogenetic concept with special emphasis on the role of drug metabolites) . Transfus Med Rev . 1990;4:69–77
  16. Garratty G . Target antigens for red-cell-bound autoantibodies . In:  Nance SJ editors. Clinical and Basic Science Aspects of Immunohematology . Arlington, VA: American Association of Blood Banks; 1991;p. 33–72
  17. Garratty G . Drug-induced immune hemolytic anemia . In:  Garratty G editors. Immunobiology of Transfusion Medicine . New York, NY: Dekker; 1994;p. 523–551
  18. Shulman NR , Reid DM . Mechanisms of drug-induced immunologically mediated cytopenias . Tranfus Med Rev . 1993;7:215–229
  19. Molthan L , Reidenberg MM , Eichman MF . Positive direct Coombs tests due to cephalothin . N Engl J Med . 1967;277:123–125
  20. Gralnick HR , Wright LD , McGinniss MH . Coombs’ positive reactions associated with sodium cephalothin therapy . JAMA . 1967;199:725–726
  21. Spath P , Garratty G , Petz L . Studies on the immune response to penicillin and cephalothin in humans. II. Immunohematologic reactions to cephalothin administration . J Immunol . 1971;107:860–869
  22. Ferrone S , Zanella A , Scalamogna M . Red cell metabolism in positive direct Coombs test after cephalothin therapy . Experientia . 1971;27:194–195
  23. Garratty G , Arndt P , Nance S . Nonimmunological adsorption of proteins onto red cells treated with second and third generation cephalosporins . Transfusion . 1994;34(suppl):69S; (abstr)
  24. Zeger G , Smith L , McQuiston D , Goldfinger D . Cisplatin-induced nonimmunologic adsorption of immunoglobulin by red cells . Transfusion . 1988;28:493–495
  25. Jamin D , Demers J , Shulman I , Lam HT , Momparler R . An explanation for non-immunologic adsorption of proteins onto red blood cells (Schiff’s base reactions) . Blood . 1986;67:993–996
  26. Arndt PA , Garratty G , Isaak E , Bolger MJ . Positive direct and indirect antiglobulin tests associated with oxaliplatin can be caused by antibody and/or nonimmunologic protein adsorption . Transfusion . 2003;43:102A; (abstr)
  27. Jamin D , Shulman I , Lam HT , Aguilar S , Shields M , Cohen J , et al.   Production of a positive direct antiglobulin test due to suramin . Arch Pathol Lab Med . 1988;112:898–900
  28. Williams ME , Thomas D , Harman CP , Mintz PD , Donowitz GR . Positive direct antiglobulin tests due to clavulanic acid . Antimicrob Agents Chemother . 1985;27:125–127
  29. Garratty G , Arndt PA . Positive direct antiglobulin tests and haemolytic anaemia following therapy with beta-lactamase inhibitor containing drugs may be associated with nonimmunologic adsorption of protein onto red blood cells . Br J Haematol . 1998;100:777–783
  30. Arndt PA , Leger RM , Garratty G . Positive direct antiglobulin tests and haemolytic anemia following therapy with the beta-lactamase inhibitor, tazobactam, may also be associated with non-immunologic adsorption of protein onto red blood cells . Vox Sang . 2003;85:53
  31. Gralnick HR , McGinniss M , Elton W , McCurdy P . Hemolytic anemia associated with cephalothin . JAMA . 1971;217:1193–1197
  32. Jeannet M , Bloch A , Dayer JM , Farquet JJ , Girard JP , Cruchaud A . Cephalothin-induced immune hemolytic anemia . Acta Haematol . 1976;55:109–117
  33. Rubin RN , Burka ER . Anti-cephalothin antibody and Coombs’-positive hemolytic anemia . Ann Intern Med . 1977;86:64–65
  34. Moake JL , Butler CF , Hewell GM , Cheek J , Spruell MA . Hemolysis induced by cefazolin and cephalothin in a patient with penicillin sensitivity . Transfusion . 1978;18:369–373
  35. Broadberry RE , Farren TW , Bevin SV , Kobler JA , Yates S , Skidmore I , et al.   Tazobactam-induced haemolytic anaemia, possibly caused by non-immunological adsorption of IgG onto patient’s red cells . Transfusion Med . 2004;14:53–57
  36. Arndt P , Garratty G . Can nonspecific protein coating of RBCs lead to increased RBC destruction? Drug-treated RBCs with positive antiglobulin tests due to nonspecific protein uptake give positive monocyte monolayer assays . Transfusion . 2000;40(suppl):29S; (abstr)
  37. Nance SJ , Arndt P , Garratty G . Predicting the clinical significance of red cell alloantibodies using a monocyte monolayer assay . Transfusion . 1987;27:449–452
  38. Garratty G . Predicting the clinical significance of red cell antibodies with in vitro cellular assays . Transfus Med Rev . 1990;4:297–312
  39. Arndt PA , Garratty G . A retrospective analysis of the value of monocyte monolayer assay results for predicting the clinical significance of blood group alloantibodies . Transfusion . 2004;44:1273–1281
  40. Hardman JG , Gilman AG , Limbird LE . In: Goodman & Gilman’s The Pharmacological Basis of Therapeutics . (ed 9). New York, NY: McGraw-Hill; 1996;
  41. Manoharan A , Kot T . Cephalexin-induced hemolytic anemia . Med J Aust . 1987;147:202
  42. Salama A , Göttsche B , Schleiffer T , Mueller-Eckhardt C . ‘Immune complex’ mediated intravascular hemolysis due to IgM cephalosporin-dependent antibody . Transfusion . 1987;27:460–463
  43. Shulman IA , Arndt PA , McGehee W , Garratty G . Cefotaxime-induced immune hemolytic anemia due to antibodies reacting in vitro by more than one mechanism . Transfusion . 1990;30:263–266
  44. Malaponte G , Arcidiacono C , Mazzarino C , Pelligra S , Li Volti G , Bevelacqua V , et al.   Cephalosporin-induced hemolytic anemia in a Sicilian child . Hematology . 2000;5:327–334
  45. Garratty G , Nance S , Lloyd M , Domen R . Fatal immune hemolytic anemia due to cefotetan . Transfusion . 1992;32:269–271
  46. Ehmann WC . Cephalosporin-induced hemolysis (A case report and review of the literature) . Am J Hematol . 1992;40:121–125
  47. Chenoweth CE , Judd WJ , Steiner EA , Kauffman CA . Cefotetan-induced immune hemolytic anemia . Clin Infect Dis . 1992;15:863–865
  48. Eckrich RJ , Fox S , Mallory D . Cefotetan-induced immune hemolytic anemia due to the drug-adsorption mechanism . Immunohematology . 1994;10:51–54
  49. Peano GM , Menardi G , Quaranta L , Abello P , Landra M , Fenoglio S . A rapidly fatal case of immune hemolytic anemia due to cefotetan . Vox Sang . 1994;66:84–85
  50. Garratty G , Leger RM , Arndt PA . Severe immune hemolytic anemia associated with prophylactic use of cefotetan in obstetric and gynecologic procedures . Am J Obstet Gynecol . 1999;181:103–104
  51. Arndt PA , Leger RM , Garratty G . Serology of antibodies to second- and third-generation cephalosporins associated with immune hemolytic anemia and/or positive direct antiglobulin tests . Transfusion . 1999;39:1239–1246
  52. Stroncek D , Proctor JL , Johnson J . Drug-induced hemolysis (Cefotetan-dependent hemolytic anemia mimicking an acute intravascular immune transfusion reaction) . Am J Hematol . 2000;64:67–70
  53. Naylor CS , Steele L , His R , Margolin M , Goldfinger D . Cefotetan-induced hemolysis associated with antibiotic prophylaxis for cesarean delivery . Am J Obstet Gynecol . 2000;182:1427–1428
  54. Moes GS , MacPherson BR . Cefotetan-induced hemolytic anemia (A case report and review of the literature) . Arch Pathol Lab Med . 2000;124:1344–1346
  55. Marques MB , Carr KD , Brumfield CG , Huang ST . A pregnant patient with sickle cell disease and cefotetan-induced immune hemolysis . Lab Med . 2000;31:541–543
  56. Ray EK , Warkentin TE , O’Hoski PL , Gregor P . Delayed onset of life-threatening immune hemolysis after perioperative antimicrobial prophylaxis with cefotetan . Can J Surg . 2000;43:461–462
  57. Arndt PA . Practical aspects of investigating drug-induced immune hemolytic anemia due to cefotetan or ceftriaxone—A case study approach . Immunohematology . 2002;18:27–32
  58. Leger RM , Arndt PA , Garratty G . A negative of very weakly positive DAT should not exclude investigation of drug-induced immune hemolytic anemia . Transfusion . 2003;43:1640–1641
  59. Franchini M , Piccoli PL , Gandini G , Giuffrida A , Bressan F , De Gironcoli M , et al.   Clinical and laboratory study of an episode of cefotetan-induced severe hemolytic anemia . Hematology . 2004;9:65–69
  60. Shariatmadar S , Storry J , Sausais L , Reid ME . Cefotetan-induced immune hemolytic anemia following prophylaxis for cesarean delivery . Immunohematology . 2004;20:63–66
  61. Garratty G , Postoway N , Schwellenbach J , McMahill PC . A fatal case of ceftriaxone (Rocephin)-induced hemolytic anemia associated with intravascular immune hemolysis . Transfusion . 1991;31:176–179
  62. Bernini JC , Mustafa MM , Sutor LJ , Buchanan GR . Fatal hemolysis induced by ceftriaxone in a child with sickle cell anemia . J Pediatr . 1995;126:813–815
  63. Borgna-Pignatti C , Bezzi TM , Reverberi R . Fatal ceftriaxone-induced hemolysis in a child with acquired immunodeficiency syndrome . Pediatr Infect Dis J . 1995;14:1116–1117
  64. Moallem HJ , Garratty G , Wakeham M , Dial S , Oligario A , Gondi A , et al.   Ceftriaxone-related fatal hemolysis in an adolescent with perinatally acquired human immunodeficiency virus infection . J Pediatr . 1998;133:279–281
  65. Meyer O , Hackstein H , Hoppe B , Göbel F-J , Bein G , Salama A . Fatal immune haemolysis due to a degradation product of ceftriaxone . Br J Haematol . 1999;105:1084–1085
  66. Viner Y , Hashkes PJ , Yakubova R , Segal-Kupershmit D , Luder AS . Severe hemolysis induced by ceftriaxone in a child with sickle-cell anemia . Pediatr Infect Dis J . 2000;19:83–85
  67. Seltsam A , Salama A . Ceftriaxone-induced immune haemolysis (Two case reports and a concise review of the literature) . Intensive Care Med . 2000;26:1390–1394
  68. Falezza GC , Piccoli PL , Franchini M , Gandini G , Aprili G . Ceftriaxone-induced hemolysis in an adult . Transfusion . 2000;40:1543–1545
  69. Kim S , Song KS , Kim HO , Lee HM . Ceftriaxone induced immune hemolytic anemia (detection of drug-dependent antibody by ex-vivo antigen in urine) . Yonsei Med J . 2002;43:391–394
  70. Citak A , Garratty G , Ucsel R , Karabocuoglu M , Uzel N . Ceftriaxone-induced haemolytic anaemia in a child with no immune deficiency or haematological disease . J Paediatr Child Health . 2002;38:209–210
  71. Mattis LE , Saavedra JM , Shan H , Shirey RS , Powell E , Oliva-Hemker MM . Life-threatening ceftriaxone-induced immune hemolytic anemia in a child with Crohn’s disease . Clin Pediatr . 2004;43:175–178
  72. Kakaiya R , Cseri J , Smith S , Silberman S , Rubinas TC , Hoffstadter A . A case of acute hemolysis after ceftriaxone (immune complex mechanism demonstrated by flow cytometry) . Arch Pathol Lab Med . 2004;128:905–907
  73. Viraraghavan R , Chakravarty AG , Soreth J . Cefotetan-induced haemolytic anaemia. A review of 85 cases . Adverse Drug React Toxicol Rev . 2002;21:101–107
  74. Davenport RD , Judd WJ , Dake LR . Persistence of cefotetan on red blood cells . Transfusion . 2004;44:849–852
  75. Bateman ST , Hu E , Lane C , Quillen K , Pelton SI . Antibody to ceftriaxone in HIV pediatric patients and potential implications for RBC hemolysis . Blood . 2002;100:48b; (abstr)
  76. Arndt PA , Garratty G . Cross-reactivity of cefotetan and ceftriaxone antibodies, associated with hemolytic anemia, with other cephalosporins and penicillin . Am J Clin Pathol . 2002;118:256–262
  77. Arndt P , Garratty G . Is severe immune hemolytic anemia, following a single dose of cefotetan, associated with the presence of “naturally-occurring” anti-cefotetan? . Transfusion . 2001;41(suppl):24S; (abstr)
  78. Sosler SD , Behzad O , Garratty G , Lee CL , Postoway N , Khomo O . Acute hemolytic anemia associated with a chlorpropamide-induced apparent auto-anti-Jka . Transfusion . 1984;24:206–209
  79. Shirey RS , Morton SJ , Lawton KB , Lowell C , Kickler TS , Ness PM . Fenoprofen-induced immune hemolysis . Am J Clin Pathol . 1988;89:410–414
  80. Brown JL . Incomplete labeling of pharmaceuticals (A list of “inactive” ingredients) . N Engl J Med . 1983;309:439–441
  81. Law IP , Wickman CJ , Harrison BR . Coombs’-positive hemolytic anemia and ibuprofen . South Med J . 1979;72:707–710
  82. Salama A , Mueller-Eckhardt C , Kissel K , Pralle H , Seeger W . Ex vivo antigen preparation for the serological detection of drug-dependent antibodies in immune haemolytic anaemias . Br J Haematol . 1984;58:525–531

PII: S0037-1963(05)00057-0

doi: 10.1053/j.seminhematol.2005.04.004

Seminars in Hematology
Volume 42, Issue 3 , Pages 137-144 , July 2005