A Case of Copper Deficiency‐Induced Pancytopenia With Maintenance Hemodialysis Outpatient Treated With Polaprezinc

Zinc deficiency has been reported in hemodialysis (HD) patients and causes erythropoietin-resistant anemia (3). These HD patients sometimes receive oral adjuvant zinc therapy using polaprezinc (Promac, Zeria Pharmaceuticals, Tokyo, Japan). We report a rare case of pancytopenia due to polaprezinc-induced copper deficiency in a HD patient without a history of gastrointestinal surgery. Erythropoietin-resistant anemia was improved by drinking hot chocolate. We found that hot chocolate was useful to correct copper deficiency safely in a HD patient. A 46-year-old Japanese non-diabetic woman who had been receiving dialysis therapy including peritoneal dialysis for more than 10 years complained of low appetite and general fatigue. She had no history of an abnormal blood cell count prior to the event. On physical examination, her conjunctiva was pale but other examinations were normal. Laboratory data showed pancytopenia. Further serological study showed that zinc was remarkably elevated (182 μg/dL), while copper was significantly decreased (4 μg/dL). She had been taking oral polaprezinc (zinc content, 34 mg/day) for more than 10 years. We diagnosed polaprezinc-induced pancytopenia associated with copper deficiency and polaprezinc was discontinued. Although the serum zinc level gradually decreased, pancytopenia was not improved because of the lowered serum copper level. Hence, we urged her to drink hot chocolate (containing about 0.23 mg copper/cup) as a copper substitution therapy. After that, pancytopenia gradually resolved with improvement of serum zinc and copper levels (Fig. 1). There are few case reports of anemia due to copper deficiency in HD patients (2). Those cases involved enteral nutrition, which was different from our case. We thought that expansion of the zinc/copper ratio was an important factor in the progression of copper deficiency-induced pancytopenia. This patient had a low appetite before pancytopenia appeared. However, we had continued oral administration of polaprezinc. It may have caused by rapid expansion of the zinc/copper ratio. We need to consider the possibility of copper deficiency in outpatient dialysis treatment in the setting of erythropoietin-resistant anemia. Knowledge of the detailed mechanism by which copper is absorbed from the diet is incomplete. It is generally known that copper and zinc are absorbed in the stomach and small intestine (5). Excessive serum zinc levels cause an upregulation of synthesis of metallothionein (MTO) in enterocytes. MTO has a high affinity for transition metals, forming mercaptide bonds through its multiple cysteine residues. Copper displaces zinc because of its higher affinity for MTO (4). When there is an excess of zinc, copper is not absorbed into the intestinal tract and leads to hypocupremia. Another important point to note is that serum copper could be corrected without elevation of potassium and phosphate levels by drinking a cup of hot chocolate. We suggest that hot chocolate can safely correct serum copper levels in dialysis patients. In conclusion, this case suggests that serum trace elements in long-term HD patients should be closely monitored to prevent over-supplementation. We FIG. 1. Clinical course of patient. Cu, copper; DA, darbepoetinalfa; ESA, erythropoiesis stimulating agent; Hb, hemoglobin; Plt, platelets; WBC, white blood cells; Zn, zinc. 422 Letters to the Editor