Copper Deficiency Remains An Underappreciated Cause of Ineffective Hematopoiesis

Copper deficiency has long been recognized as cause of hematopoietic dysfunction, and diagnosis is straightforward if it is pursued. Over a three year period, we diagnosed copper deficiency in seven pts referred to our university-based hematology and BMT outpatient clinics for evaluation and treatment of myelodysplastic syndrome (MDS) or neutropenia/anemia. This represents approximately 3% of new outpatient referrals carrying an ICD-9 code corresponding to MDS or neutropenia. Patient characteristics are shown in Table 1. Three of the seven pts carried a presumptive diagnosis of MDS, and one had received several months of decitabine therapy. Two patients were actually referred for consideration of stem cell transplantation; the others were referred for evaluation of cytopenias. Six of the seven patients had been evaluated by a hematologist prior to referral. Only 3 of 7 pts in our series had recognized risk factors for copper deficiency such as prior gastric bypass or other GI dysfunction; postulated risk factors in the other pts are included in Table1. All pts in our series were anemic and leukopenic, with absolute neutropenia at presentation. In contrast, platelet counts were normal or elevated in all pts, consistent with most previous reports. Five of the seven pts in our series had neuropathy or myelopathy of variable severity. The hematologic abnormalities responded rapidly and completely to oral and/or IV copper replacement in all pts, although neurologic recovery was slow and incomplete.

Conclusions: Our experience indicates that copper deficiency is a relatively common cause of neutropenia and anemia, and the consequences of missing the diagnosis may be substantial, including performance of unnecessary transfusion, chemotherapy, and even stem cell transplantation. Normal or elevated platelet counts and concomitant neuropathy or myelopathy are important clues to the diagnosis. Furthermore, copper deficiency must be considered even in pts without obvious GI absorption abnormalities. Serum copper and ceruloplasmin assays should be incorporated into the routine evaluation of most pts with cytopenias and suspected MDS.