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Copper Deficiency Anemia Is Not Uncommon in a Hematology Practice.

Jason D. Huff, Yi-Kong Keung, Mohan C. Thakuri, Michael W. Beaty, John Owen and Istvan Molnar

Abstract

Copper deficiency is a rare cause of anemia. Copper deficiency anemia has been described in patients on total parenteral or forced enteral nutrition deficient in copper, post gastric resection, short bowel syndrome (from prior intestinal resections or gastric by-pass) or malabsorptive disease states such as Crohn’s or celiac disease, and in patients taking excessive amounts of zinc. We have shown that in the NHANES II adult population, low copper levels are associated with increased risk of unexplained anemia (Molnar et al., abstract submitted at this meeting). We recently started to routinely check serum copper levels in patients referred to our hematology clinic for evaluation of unexplained anemia. Between December 2003 and March 2005, we found seven patients who had lower than normal copper levels and unexplained anemia. Six out of the seven patients were treated with copper supplementation and had improvement in their hematological abnormalities. Most patients had undergone an expensive, unproductive diagnostic evaluation before copper deficiency was diagnosed. In five of the seven patients, the anemia was severe. Two patients were red cell transfusion-dependent. Six out of seven patients had associated granulocytopenia. Even in the presence of severe granulocytopenia, recurrent, clinically significant infections were rare. Thrombocytopenia was present in two patients. Peripheral blood findings were non-specific. Bone marrow findings varied with two patients demonstrating normal marrow histology, two patients with hypercellular marrow, one exhibited myeloid maturation arrest, and the remaining two patients demonstrating frank dysplastic changes with ring sideroblasts. Five out of seven patients had cytogenetic examination of the bone marrow revealing a normal karyotype. The response to copper treatment was frequently rapid, and improvement in anemia and neutropenia was evident within a few weeks. The characteristics of our patient population are outlined in the table below. In conclusion, copper deficiency anemia is not uncommon in a hematology practice. Copper deficiency should be considered in patients presenting with unexplained anemia associated with neutropenia, a history of malabsorption, gastrointestinal resection or gastric bypass, nephrotic syndrome, or dysplastic bone marrow changes with a normal karyotype analysis. The details of clinical and pathological features of the patients will be presented in detail at the meeting.

CaseAge /SexAnemiaNeutropeniaBone Marrow FindingsCo-morbid conditionsCopper Level μg/dLHematological Response to Copper Treatment
171 /FemaleTransfustion dependentYesHypercellularChronic diarrhea, nephrotic syndrome, diabetes mellitus< 10Partial
260 /MaleYesYesNormalChronic diarrhea, renal failure status-post renal transplant, celiac sprue41Not treated Complete
333 /FemaleMildYesRinged sideroblasts, myeloid and erythroid dysplasiaNone37Complete response
432 /FemaleYesYesMyeloid maturation arrestGastric bypass surgery< 10Complete response
545 /FemaleTransfusion dependentYesRinged sideroblasts, DyserythropoiesisBillroth II operation< 10Complete response
642 /FemaleMildYesHypercellular, myeloid maturation arrestNone< 10Complete response
751 /MaleYesNoNormalAcute myeoid leukemia, short bowel syndrome45Partial

Copper Deficiency Anemia Patient Characteristics