Acute pure red cell aplasia associated with allopurinol therapy

Lin, Ying‐Wei; Okazaki, Shin; Hamahata, Keigo; Watanabe, Kenichiro; Usami, Ikuya; Yoshibayashi, Muneo; Akiyama, Yuichi; Kubota, Masaru

doi:10.1002/(sici)1096-8652(199907)61:3<209::aid-ajh9>3.0.co;2-v

Cited by 14 publications

(12 citation statements)

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“…Since topiroxostat is not dialyzable, the dose reduction is not required even in patients with lowered renal function. 16 Therefore, it seems that topiroxostat exerted the effect even at low doses in HD patients. Conversely, allopurinol which has been conventionally used as a xanthine oxidase inhibitor has been basically administered at lower doses to patients with renal failure than those to patients with normal renal function, because it has adverse effects such as hypersensitivity and bone marrow toxicity.…”

Section: Discussionmentioning

confidence: 99%

“…To maintain serum uric acid levels below 7.0 mg/dL, an additional prescription was not needed in 85% of patients in the topiroxostat‐treated period, whereas only 59% of patients did not required it in the allopurinol‐treated period. Since topiroxostat is not dialyzable, the dose reduction is not required even in patients with lowered renal function . Therefore, it seems that topiroxostat exerted the effect even at low doses in HD patients.…”

Section: Discussionmentioning

confidence: 99%

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The effect of small dose of topiroxostat on serum uric acid in patients receiving hemodialysis

Nagaoka

Tanaka

Yoshimoto

et al. 2017

Hemodialysis International

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

The effect of small dose of topiroxostat on serum uric acid in patients receiving hemodialysis

Nagaoka

Tanaka

Yoshimoto

et al. 2017

Hemodialysis International

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“…Allopurinol is known to cause anaemia symptoms, such as macrocytic anaemia and aplastic anaemia, as side effects in humans and rodents (Chao, Yang, & Lee, ; Kim et al, ; Lin et al, ). In particular, aplastic anaemia which is a serious condition and is clinically problematic.…”

Section: Discussionmentioning

confidence: 99%

Perfecting a high hypoxanthine phosphoribosyltransferase activity–uricase KO mice to test the effects of purine‐ and non‐purine‐type xanthine dehydrogenase (XDH) inhibitors

Hosoya

Uchida

Shibata

et al. 2020

British J Pharmacology

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Background and Purpose: Purine metabolism in mice and human differ in terms of uricase (Uox) activity as well as hypoxanthine phosphoribosyltransferase (HPRT) activity. The aim of this study was the establishment of high HPRT activity-Uox knockout (KO) mice as a novel hyperuricaemic model. Then to investigate the effects of purine-type xanthine dehydrogenase (XDH) inhibitor, allopurinol, and non-purinetype XDH inhibitor, topiroxostat, on purine metabolism. Experimental Approach: A novel hyperuricaemic mouse model was established by mating B6-ChrXC MSM mice with uricase KO mice. The pharmacological effects of allopurinol and topiroxostat were explored by evaluating urate, hypoxanthine, xanthine and creatinine in the plasma and urine of these model mice. Furthermore, we analysed the effect of both drugs on erythrocyte hypoxanthine phosphoribosyltransferase activity. Key Results: Plasma urate level and urinary urate/creatinine ratio significantly decreased after administration of allopurinol 30 mgÁkg −1 or topiroxostat 1 mgÁkg −1 for 7 days. The urate-lowering effect was equivalent for allopurinol and topiroxostat.However, the urinary hypoxanthine/creatinine ratio and xanthine/creatinine ratio after treatment with topiroxostat were significantly lower than for allopurinol. In addition, the urinary oxypurine/creatinine ratio was significantly lowered after treatment with topiroxostat, but allopurinol elicited no such effect. Furthermore, allopurinol inhibited mouse erythrocyte hypoxanthine phosphoribosyltransferase, while topiroxostat did not. Conclusions and Implications:High hypoxanthine phosphoribosyltransferase activity-uricase KO mice were established as a novel hyperuricaemic animal model.In addition, topiroxostat, a non-purine-type xanthine dehydrogenase inhibitor, elicited a potent plasma urate-lowering effect. However, unlike allopurinol, topiroxostat did not perturb the salvage pathway, resulting in lowered total oxypurine excretion.Abbreviations: BUN, blood urea nitrogen; CRP, C-reactive protein; FE, fractional excretion; HPRT, hypoxanthine phosphoribosyltransferase; IMP, inosine 5 0 -monophosphate; KO, knockout; PRPP, 5-phosphoribosyl-1-pyrophosphate; ULE, urate-lowering effect; Uox, urate oxidase (uricase); WT, wild-type; XDH, xanthine dehydrogenase.Takuji Hosoya and Makoto Hosoyamada contributed equally to this work.

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“…Some drugs have also been implicated in the development of PRCA, most notably phenytoin, azathioprine, and isoniazid [2]. Allopurinol has been associated with nine cases of aplastic anemia but with only two cases of PRCA in the medical literature [3,4]. We report a third case linking allopurinol to the development of PRCA.…”

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confidence: 92%

Allopurinol‐induced pure red cell aplasia

2003

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Acquired pure red cell aplasia (PRCA) is a rare condition characterized by a profound anemia associated with reticulocytopenia and bone marrow remarkable for the absence of erythroid precursors while other cell lineages are preserved (see [1] for review). Although PRCA is most often idiopathic in the adult, associations with several conditions have been clearly established, including systemic lupus erythematosus, thymomas, lymphomas, ABO-incompatible blood transfusion, and viral infections, most notably parvovirus B19 and viral hepatitis. Some drugs have also been implicated in the development of PRCA, most notably phenytoin, azathioprine, and isoniazid [2]. Allopurinol has been associated with nine cases of aplastic anemia but with only two cases of PRCA in the medical literature [3,4]. We report a third case linking allopurinol to the development of PRCA.T.M. is a 79-year-old man with coronary artery disease and hypertension who was admitted to the hospital with the chief complaint of shortness of breath of 1-week duration. Physical examination was remarkable for extreme pallor without icterus, lymphadenopathy, or splenomegaly, and stool guaiac test was negative. His CBC revealed a hemoglobin of 7.9 g/dL, a hematocrit of 22.4%, an MCV of 109 fL, a RDW of 17.1%, a white blood cell count of 6.1 × 10 3 c/ l, a platelet count of 367,000 c/ l, and a normal leucocyte differential count. The peripheral blood smear showed anisocytosis with macrocytosis. Initial assessment revealed that the patient had suffered a myocardial infarction. CBC performed 3 months prior to his admission was normal with a hematocrit of 44%. Initial workup excluded vitamin B 12 , folate, and iron deficiencies as well as bleeding and hemolysis. Bone marrow biopsy showed moderate hypocellularity, with maturing granulocytic and megakaryocytic lineage. Most interestingly, the virtual absence of erythroid precursors was conspicuous. Flow cytometry revealed a small monoclonal population of mature lymphocytes with kappa light chain restriction expressing CD19, CD20, and CD22 surface antigens. Serum titers for parvovirus B19 and viral hepatitis antibodies were negative. A lupus screen was unremarkable. Because the patient had been started on allopurinol 8 weeks earlier and in view of the association between PRCA and allopurinol in two reports, this medication was discontinued. The patient was transfused to a hematocrit of 31% and discharged from the hospital. Without any further therapeutic intervention or transfusion, his hematocrit rose to 36% eight weeks later. A bone marrow biopsy performed then revealed a normal cellularity with maturing trilineage hematopoiesis and adequate erythroid precursors. Although the patient has an underlying low-grade lymphoproliferative disorder, the prompt resolution of the PRCA after discontinuation of allopurinol, along with the exclusion of any other therapeutic intervention, strongly argues in favor of a toxic drug effect. This is the third report linking the intake of allopurinol to the development of PRCA and st...

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Acute pure red cell aplasia associated with allopurinol therapy

Cited by 14 publications

References 14 publications

The effect of small dose of topiroxostat on serum uric acid in patients receiving hemodialysis

The effect of small dose of topiroxostat on serum uric acid in patients receiving hemodialysis

Perfecting a high hypoxanthine phosphoribosyltransferase activity–uricase KO mice to test the effects of purine‐ and non‐purine‐type xanthine dehydrogenase (XDH) inhibitors

Allopurinol‐induced pure red cell aplasia

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