Anemia Induced by Amphotericin B

Brandriss, Michael W.; Wolff, Sheldon M.; Moores, Russell R.; Stohlman, Frederick

doi:10.1001/jama.1964.03070090013003

Cited by 53 publications

(24 citation statements)

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“…In all other patients, at a point where the degree of anemia would be expected to stimulate the production of high erythropoietin levels, none could be detected in either serum or 24-h urine collections. DISCUSSION Anemia occurs in more than 95% of patients requiring prolonged amphotericin B therapy (4,10). In one study, the mean hematocrit fell from 41% before therapy to 27% at the completion of therapy (4).…”

Section: Methodsmentioning

confidence: 99%

“…DISCUSSION Anemia occurs in more than 95% of patients requiring prolonged amphotericin B therapy (4,10). In one study, the mean hematocrit fell from 41% before therapy to 27% at the completion of therapy (4). Defective iron reutilization is present in many systemic mycotic infections and may in part be responsible for their anemia of chronic infection (6, 7).…”

Section: Methodsmentioning

confidence: 99%

“…Although it can be a life-saving drug, its use is limited by significant toxic reactions: fever, malaise, anorexia, phlebitis, azotemia, hypokalemia, and anemia occur commonly (3)(4)(5)11). The anemia is normocytic and normochromic, with a reticulocyte count inappropriately low for the degree of hemoglobin reduction (4). Although there is some decrease in erythrocyte survival associated with the early stages of amphotericin B treatment of systemic mycoses (4), the cause for the amphotericininduced anemia appears to be reduced erythrocyte production.…”

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confidence: 99%

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Erythropoietin Concentration in Amphotericin B-Induced Anemia

MacGregor

Bennett

Erslev

1978

Antimicrob Agents Chemother

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Amphotericin B was given to six patients with systemic fungal infections. A dose averaging 1.78 g, administered from 42 to 144 days, was associated with a fall in hematocrit to a mean value of 25.8%. Despite this degree of anemia, no elevation of erythropoietin concentrations in urine or serum could be detected. Thus, amphotericin appears to cause anemia by inhibiting erythropoietin production rather than by suppressing bone marrow activity directly.

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Section: Methodsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

mentioning

confidence: 99%

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Erythropoietin Concentration in Amphotericin B-Induced Anemia

MacGregor

Bennett

Erslev

1978

Antimicrob Agents Chemother

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“…In cases of prolonged therapy (ie, more than 1 month), anemia occurs in more than 90% of patients. 3,5 The anemia produced is normocytic and normochromic, and reticulocyte numbers in anemic patients are below the normal range. 5,6 It was concluded that this anemia is caused by a drug-induced suppression of erythrocyte production rather than by an increased rate of erythrocyte destruction.…”

Section: Introductionmentioning

confidence: 99%

“…3,5 The anemia produced is normocytic and normochromic, and reticulocyte numbers in anemic patients are below the normal range. 5,6 It was concluded that this anemia is caused by a drug-induced suppression of erythrocyte production rather than by an increased rate of erythrocyte destruction. In spite of anemia, AmB-treated patients show low plasma levels of erythropoietin (EPO), which is markedly induced in case of anemia with other etiologies.…”

Section: Introductionmentioning

confidence: 99%

Amphotericin B blunts erythropoietin response to hypoxia by reinforcing FIH-mediated repression of HIF-1

Yeo

Ryu

Cho

et al. 2006

Blood

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Amphotericin B (AmB) is widely used for treating severe systemic fungal infections. However, long-term AmB treatment is invariably associated with adverse effects such as anemia. The erythropoietin (EPO) suppression by AmB has been proposed to contribute to the development of anemia. However, the mechanism whereby EPO is suppressed remains obscure. In this study, we investigated the possibility that AmB inhibits the transcription of the EPO gene by inactivating HIF-1, which is a known key transcription factor and regulator of EPO expression. EPO mRNA levels were markedly attenuated by AmB treatment both in rat kidneys and in Hep3B cells. AmB inactivated the transcriptional activity of HIF-1␣, but did not affect the expression or localization of HIF-1 subunits. Moreover, AmB was found to specifically repress the C-terminal transactivation domain (CAD) of HIF-1␣, and this repression by AmB required Asn803, a target site of the factor-inhibiting HIF-1 (FIH); moreover, this repressive effect was reversed by FIH inhibitors. Furthermore, AmB stimulated CAD-FIH interaction and inhibited the p300 recruitment by CAD. We propose that this mechanism underlies the unexplained anemia associated with AmB therapy.

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Toxicity of Amphotericin B in Children With Cancer

Wilson¹

1979

Arch Pediatr Adolesc Med

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\s=b\ The pattern of amphotericin B toxicity was assessed retrospectively in a group of 20 children with cancer who had received one or more courses of the drug for treatment of systemic fungal infection. Azotemia was the most frequent complication, developing during 23 of 24 treatment courses. Other major toxic effects, in decreasing order of frequency, were anemia, hypokalemia, thrombocytopenia, and neutropenia. Infusion side effects, including drug-related fever, chills, and nausea, were also frequently seen. Seventeen of 20 patients were treated for disseminated histoplasmosis. Nineteen of 20 patients had acute leukemia. Although interaction with other agents could not be excluded, amphotericin B appeared to be the major causative agent for the toxic reactions noted. In no patient, however, was administration of amphotericin B stopped because of drug toxicity.(Am J Dis Child 133: [731][732][733][734] 1979) A mphotericin remains the drug of choice for systemic antifungal chemotherapy. Its toxic effects in adults have been extensively reviewed and can be summarized as follows: (1) hematopoietic toxicity manifested primarily as anemia, (2) renal toxicity manifested as azotemia, (3) electro¬ lyte abnormalities, chiefly hypokale¬ mia, (4) rare instances of cardiotoxicity and hepatotoxicity, and (5) imme¬ diate side effects from the infusion, including chills, fever, and nausea. Characterizations of amphotericin toxicity in children are, by compari¬ son, quite limited. In a search of the literature, Cherry et al' found only 19 cases in which renal function studies were done, either during or at the completion of amphotericin thera¬ py, and only 39 cases in which specific dosages were noted. This report pre¬ sents toxicity findings in 20 patients Atlanta, GA 30333 (Dr Wilson). who were treated for at least two weeks with amphotericin B. Our intent is to characterize amphotericin toxicity in children with cancer, providing data that will serve as a baseline for future prospective stud¬ ies. SUBJECTS AND METHODSFrom 1962 to 1977, twenty-two patients with systemic fungal infections were treated for two weeks or longer with amphotericin at St Jude Children's Research Hospital, Memphis. The medical records of each child were reviewed for demographic information and for laborato¬ ry and clinical findings considered perti¬ nent to the potential toxic effects of amphotericin B. Two patients were ex¬ cluded from the study because of inade¬ quate laboratory reports. Thus, findings for 20 patients, representing 24 courses of amphotericin B, were analyzed. Selected patient characteristics on ad¬ mission to the study were as follows: (1) Eight of the 20 patients were boys; ages ranged from 1 year and 10 months to 17 years and 7 months (median, 7 years and 11 months). (2) Acute lymphoblastic leukemia was the underlying malignant disease in 17 patients. (3) One patient had acute myeloblastic leukemia and one had Wilms' tumor. (4) The underlying fungal diseases included histoplasmosis in 17 patients, and one patient each with as...

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Anemia Induced by Amphotericin B

Cited by 53 publications

References 4 publications

Erythropoietin Concentration in Amphotericin B-Induced Anemia

Erythropoietin Concentration in Amphotericin B-Induced Anemia

Amphotericin B blunts erythropoietin response to hypoxia by reinforcing FIH-mediated repression of HIF-1

Toxicity of Amphotericin B in Children With Cancer

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