Clinical Features of Hematological Disorders Caused by Copper Deficiency during Long-Term Enteral Nutrition

Abstract

Objective Copper deficiency has been reported to cause hematological disorders. However, its clinical and hematological characteristics are not fully understood. Therefore, we investigated bedridden patients suffering from copper deficiency and tried to clarify the clinical features of hematological disorders caused by this condition.Patients and Methods Five patients with typical copper deficiency who had been dependent upon enteral nutrition for a long period of time due to various diseases were investigated. We measured hematological parameters and observed the response to copper supplementation therapy and the recovery process of hematological disorders.Results Their mean age was 82.6±10.4 years and the mean duration of enteral nutrition was 16.4±5.2 months. Their serum copper concentration was extremely decreased (range, 3 to 8 g/dl). All five patients had anemia and neutropenia. On the other hand, platelet count remained within the normal range. After copper supplementation therapy, hemoglobin concentration increased from 6.8±0.7 g/dl to 9.9±0.7 g/dl within a few months (p<0.01). Neutrophil count also increased from 750±370/ l to 3,690±1,210/ l in a few weeks (p<0.01). Mean corpuscular volume (MCV) decreased from 94.3±7.3 fl to 86.0±4.8 fl (p<0.05). Elevated serum ferritin and erythropoietin (EPO) levels were normalized after the improvement of anemia.Conclusion Bicytopenia (anemia and neutropenia) with normal platelet count is a feature of hematological disorders caused by copper deficiency. MCV tends to indicate macrocytic anemia. Serum ferritin and EPO levels are elevated. These hematological abnormalities are improved within a few months after copper supplementation therapy.

Interaction between anemia and blood levels of iron, zinc, copper, cadmium and lead in children

“…Also, Nagano et al shows that copper supplementation decreased MCV levels in humans. 20 At the same time the results show that the negative correlation is between serums copper concentration and ferritin, hemoglobin values of serum in this study (r= -0.203 p<0.01, r= -0.392 p<0.001 respectively). We observed that high copper negatively affected hematological parameters in this research.…”

Phase I Study of Copper-Binding Agent ATN-224 in Patients with Advanced Solid Tumors

“…Neutropenia has been described previously in copper deficiency (18) and may be due to arrested maturation of granulocytes (19). Grade 3 to 4 neutropenia was also seen in the phase II study of tetrathiomolybdate (16).…”

Clinicopathological Analysis of Hematological Disorders in Tube-Fed Patients with Copper Deficiency

“…Such patients sometimes have trace element deficiencies, and the clinical sequelae of these deficiencies may not be very obvious (3,4). Some such patients have anemia, often caused by iron deficiency due to gastrointestinal bleeding, but severe copper deficiency usually presents with anemia and or leucopenia (5)(6)(7). There have been reports of ringed sideroblasts and vacuolation of erythroid and myeloid precursors in patients with severe copper deficiency (6,(8)(9)(10)(11)(12)(13)(14)(15)…”