To describe a case of acute hemolysis associated temporally with administration of trimethoprim/ sulfamethoxazole (TMP/SMX) in a patient with AIDS, review the available literature on TMP/SMX-induced hemolytic anemia, and discuss possible drug- and disease-related factors that may have contributed to the episode of hemolysis.
Case Summary:
A precipitous decrease in red blood cell count, hemoglobin, and hematocrit occurred shortly after a black woman with AIDS received a single intravenous dose of TMP/SMX for Pneumocystis carinii pneumonia. Following drug discontinuation and repeated transfusions, the patient's hematologic indices returned to baseline.
Literature Sources:
References were obtained using MEDLINE searches, the bibliographies of articles identified during the searches, review articles, and standard textbooks.
Data Synthesis:
Of the two different mechanisms of TMP/SMX-induced hemolytic anemia, the reaction is most likely to occur via dose-related oxidative disruption of the erythrocyte membrane in subpopulations deficient in glucose-6-phosphate dehydrogenase (G6PD) activity. In the US, G6PD deficiency most frequently is encountered among blacks. The potential for hemolysis may be further increased in G6PD-deficient AIDS patients, who also appear to lack adequate intracellular glutathione, which is essential for protecting the erythrocyte membrane from oxidative damage. Although an assay for G6PD activity was not conducted, the case circumstances were consistent with TMP/SMX-induced hemolysis in a G6PD-deficient patient.
Conclusions:
Black patients with AIDS who are receiving relatively high (≥50 mg/kg/d) dosages of TMP/SMX should be monitored closely for signs and symptoms of hemolytic anemia.
Get full access to this article
View all access options for this article.
References
1.
BeutlerE. Glucose-6-phosphate dehydrogenase deficiency. N Engl J Med1991; 324: 169–74.
2.
TabbaraIA. Hemolytic anemias: Diagnosis and management. Med Clin North Am1992; 76: 649–68.
3.
WallachJ. Interpretation of laboratory tests: A synopsis of laboratory medicine. 5th ed.Boston: Little, Brown, 1992: 298–9,312–6.
4.
SacherRAMcPhersonRA. Widmann's clinical interpretation of laboratory tests. 10th ed.Philadelphia: FA Davis, 1991: 33–58, 116–8,422–5.
5.
GreenbergMS. Heinz body hemolytic anemia. Arch Intern Med1976; 136: 153–5.
6.
ZeringerHPittiglioDH. Hemolytic anemias: Intracorpuscular defects. III. The hemoglobinopathies. In: PittiglioEHSacherRA, eds. Clinical hematology and fundamentals of hemostasis. Philadelphia: FA Davis, 1987: 106–16.
7.
BeutlerE. Erythrocyte disorders: Anemias due to increased destruction of erythrocytes with enzyme deficiencies. In: WilliamsWJBeutlerEErslevAJLichtmanMA, eds. Hematology. 4th ed.New York: McGraw Hill Publishing, 1990: 591–606.
ZonLIGroopmanJE. Hematologic manifestations of the human immunodeficiency virus (HIV). Semin Hematol1988; 25: 208–18.
10.
MatthewsSJCersosimoRJSpivackML. Zidovudine and other reverse transcriptase inhibitors in the management of human immunodeficiency virus-related disease. Pharmacotherapy1991; 11: 419–49.
11.
SattlerFRCowanRNielsonDMRuskinJ. Trimethoprim-sulfamethoxazole compared with pentamidine for treatment of Pneumocystis carinii pneumonia in the acquired immunodeficiency syndrome. Ann Intern Med1988; 109: 280–7.
12.
HoigneRMalinverniRSchopferK. Sulfonamides and miscellaneous antibacterial and antiviral drugs. In: DukesMNG, ed. Meyler's side effects of drugs. 11th ed.New York: Elsevier, 1988: 603–13.
13.
BerkowitzFE. Hemolysis and infection: Categories and mechanisms of their interrelationship. Rev Infect Dis1991; 13: 1151–62.
14.
PuppoFTorresinALottiGBalleariEOrlandoGIndiveriF. Autoimmune hemolytic anemia and human immunodeficiency virus (HIV) infection. Ann Intern Med1988; 109: 249–50.
15.
RapoportAPRowJMMcMicanA. Life-threatening autoimmune hemolytic anemia in a patient with the acquired immunodeficiency syndrome. Transfusion1988; 28: 190–1.
ZinkhamWH. Unstable hemoglobins and the selective hemolytic action of sulfonamides (editorial). Arch Intern Med1977; 137: 1365–6.
20.
ValentineWNTanakaKRPagliaDE. Hemolytic anemias and erythrocyte enzymopathies. Ann Intern Med1985; 103: 245–7.
21.
HochsteinP. Perspectives on hydrogen peroxide and drug-induced hemolytic anemia in glucose-6-phosphate dehydrogenase deficiency. Free Radic Biol Med1988; 5: 387–92.
22.
MeloonJR. Hemolytic anemias: Intracorpuscular defects II. Hereditary enzyme deficiencies. In: PittiglioEHSacherRA, eds. Clinical hematology and fundamentals of hemostasis. Philadelphia: FA Davis, 1987: 99–105.
23.
Koch-WeserJSidelVWDexterMParishCFinerDCKanarekP. Adverse reactions to sulfisoxazole, sulfamethoxazole, and nitrofurantoin: Manifestations and specific reaction rates during 2,118 courses of therapy. Arch Intern Med1971; 128: 399–404.
24.
GleckmanRAlvarezSJoubertDW. Trimethoprim-sulfamethoxazole. Am J Hosp Pharm1979; 36: 893–906.
25.
BöttigerLEFurhoffAKHolmbergL. Drug-induced blood dyscrasias. Acta Med Scand1979; 205: 457–61.
26.
JickH. Adverse reactions to trimethoprim-sulfamethoxazole in hospitalized patients. Rev Infect Dis1982; 4: 426–8.
27.
LawsonDHPaiceBJ. Adverse reactions to trimethoprim-sulfa-methoxazole. Rev Infect Dis1982; 4: 429–33.
HeimpelHRaghavacherA. Hematological side effects of co-trimoxazole. Infection1987; 15(suppl 5): S248–53.
30.
MarkowitzNSaravolatzLD. Use of trimethoprim-sulfamethoxazole in a glucose-6-phosphate dehydrogenase-deficient population. Rev Infect Dis1987; 9(suppl 2): S218–29.
31.
Report from the International Agranulocytosis and Aplastic Anemia Study. Anti-infective drug use in relation to the risk of agranulocytosis and aplastic anemia. Arch Intern Med1989; 149: 1036–40.
32.
KeisuMWiholmBEPalmbladJ. Trimethoprim-sulphamethoxazole associated blood dyscrasias. Ten years' experience of the Swedish spontaneous reporting system. J Intern Med1990; 228: 353–60.
33.
Food and Drug Administration. Sulfonamide-induced serious adverse reactions—FDA bulletin, 1984. In: DRUGDEX drug consultsedition 81. Micromedex, Denver, CO, 1994.
34.
AllenSDWilkersonJL. The importance of glucose-6-phosphate dehydrogenase screening in a urologic practice. J Urol1972; 107: 304–5.
35.
OwusuSK. Acute haemolysis complicating co-trimoxazole therapy for typhoid fever in a patient with G.-6-P.D. deficiency (letter). Lancet1972,2: 819.
36.
ConstantopoulosAEconomopoulosPKandylasJ. Fulminant diarrhoea and acute haemolysis due to G-6-PD deficiency in salmonellosis (letter). Lancet1973; 1: 1522.
37.
ChanTKMcFadzeanAJS. Haemolytic effect of trimethoprim-sulphamethoxazole in G-6-PD deficiency. Trans R Soc Trop Med Hyg1974; 68: 61–2.
38.
ParijaAC. A clinical study of trimethoprim and sulpha-methoxazole (Septra) in the treatment of bacterial diarrhoeas. Indian J Pediatr1975; 42: 345–50.
39.
ChanTKToddDTsoSC. Drug-induced haemolysis in glucose-6-phosphate dehydrogenase deficiency. Br Med J1976; 2: 1227–9.
40.
LexomboomUUnkurapianaN. Co-trimoxazole in the treatment of typhoid fever in children with glucose-6-phosphate dehydrogenase deficiency. Southeast Asian J Trop Med Public Health1978; 9: 576–80.
41.
PayneFEJrGieseckeTF. Multiple system reaction to trimethoprim-sulfamethoxazole. South Med J1987; 80: 275–6.
42.
TaraszewskiRHarveyRRosmanP. Death from drug-induced hemolytic anemia. Postgrad Med1989; 85: 79–81.
43.
JayGDRenziFP. Evaluation of pulse oximetry in anemia from hemoglobin-h disease. Ann Emerg Med1992; 21: 572–4.
44.
PonteCDLewisMJRogersJSII. Heinz-body hemolytic anemia associated with phenazopyridine and sulfonamide. DICP Ann Pharmacother1989; 23: 140–2.
NathanDMSiegelAJBunnHF. Acute methemoglobinemia and hemolytic anemia with phenazopyridine (letter). Arch Intern Med1977; 137: 1636.
47.
FoltzerMAReeseRE. Trimethoprim-sulfamethoxazole and other sulfonamides. Med Clin North Am1987; 71: 1177–94.
48.
StevensRCLaizureSCWilliamsCLSteinDS. Pharmacokinetics and adverse effects of 20-mgAg/day trimethoprim and 100-mg/kg/day sulfamethoxazole in healthy adult subjects. Antimicrob Agents Chemother1991; 35: 1884–90.
49.
BowdenFJHarmanPJLucasCR. Serum trimethoprim and sulfamethoxazole levels in AIDS (letter). Lancet1986; 1: 853.
50.
LeeBLMedinaIBenowitzNLJacobPIIIWofsyCBMillsVJ. Dapsone, trimethoprim, and sulfamethoxazole plasma levels during treatment of Pneumocystis pneumonia in patients with the acquired immunodeficiency syndrome (AIDS): Evidence of drug interactions. Ann Intern Med1989; 110: 606–11.
51.
GaitJE. Hemolytic reactions to nitrofurantoin in patients with glucoses-phosphate dehydrogenase deficiency: Theory and practice. DICP Ann Pharmacother1990; 24: 1210–3.
52.
ArnoldPAGuglielmoBJHollanderH. Severe hypersensitivity reaction upon rechallenge with trimethoprim-sulfamethoxazole in a patient with AIDS. Drug Intell Clin Pharm1988; 22: 43–5.
53.
JohnsonMPGoodwinSDShandsJWJr. Trimethoprim-sulfamethoxazole anaphylactoid reactions in patients with AIDS: Case reports and literature review. Pharmacotherapy1990; 10: 413–6.
54.
KellyJWDooleyDPLattuadaCPSmithCE. A severe, unusual reaction to trimethoprim-sulfamethoxazole in patients infected with human immunodeficiency virus. Clin Infect Dis1992; 14: 1034–9.
55.
MartinGJPaparelloSFDeckerCF. A severe systemic reaction to trimethoprim-sulfamethoxazole in a patient infected with the human immunodeficiency virus (letter). Clin Infect Dis1993; 16: 175–6.
56.
ShearNHSpielbergSPGrantDMTangBKKalowW. Differences in metabolism of sulfonamides predisposing to idiosyncratic toxicity. Ann Intern Med1986; 105: 179–84.
57.
van der VenAJAMKoopmansPVreeTBvan der MeerJWM. Adverse reactions to co-trimoxazole in HIV infection. Lancet1991; 338: 431–3.
MarkowitzNQuinnELSaravolitzLD. Trimethoprim-sulfamethoxazole compared to vancomycin for the treatment of Staphylococcus aureus infection. Ann Intern Med1992; 117: 390–8.
