Observations on the anemia and neutropenia of human copper deficiency

Abstract

Following extensive bowel resection, a young woman experienced severe malnutrition; subsequent administration of parenteral nutrition precipitated the copper deficiency syndrome. This consisted of hypocupremia, subnormal ceruloplasmin levels, anemia, and severe neutropenia. The bone marrow was megaloblastic, vacuolated, and sideroblastic; granulocytic maturation was not observed beyond the myelocyte stage. Copper sulfate therapy was followed by a marked reticulocytosis, increase in hematocrit, and recovery of neutrophils. Additional studies indicated that both serum and urinary erythropoietin values were low; serum activity increased after copper supplementation. Abnormal granulopoiesis was demonstrated using the in vitro granulocyte colony assay. The patient's granulcoytic stem cells were normal on two occasions; however, mixing studies showed that culture of the patient's copper-deficient marrow with her copper-deficient serum yielded significantly reduced numbers of granulocyte colonies. Thus, copper appears to be a necessary element for normal hematopoiesis; lack of this trace element may result in ineffective erythropoiesis and granulopoiesis.

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

“…Dunlap et al (8) suggested that cytoplasmic vacuolization in early erythroid precursors is the first erythroid developmental change that occurs in cases of copper deficiency, because many patients with copper deficiency but without anemia exhibit this change. Most of the reported cases of copper deficiency (6,(8)(9)(10)(11)(12)(13)(14)(15), and all of the present copper-deficient subjects, exhibited cytoplasmic vacuolization of erythroid and myeloid precursors, which rapidly disappeared after copper supplementation. Although cytoplasmic vacuolization is also associated with other disorders, it may be particularly strongly associated with copper deficiency.…”

“…Copper deficiency has been observed in adult patients with inflammatory bowel disease (19,20), total parenteral nutrition (21,22), massive zinc ingestion (11) (6,(8)(9)(10)(11)(12)(13)(14)(15). Cytoplasmic vacuoles have also been found in patients with acute alcoholic intoxication (23), chloramphenicol toxicity (24), pancreatic dysfunction (25) and myeloproliferative syndromes (26).…”

“…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)…”

Engineering cord blood to improve engraftment after cord blood transplant

“…Severe anemia and neutropenia are well-recognized signs of copper deficiency, resulting from ineffective erythropoiesis and granulopoiesis due to the arrest of progenitor cell maturation (45)(46)(47). Similar effects can be induced by using a high affinity copper chelator which decreases the intracellular copper content (48 had engraftment from the expanded cord at the time of engraftment while the rest engrafted from the unmanipulated unit.…”

Cocoa Supplementation for Copper Deficiency Associated with Tube Feeding Nutrition

“…Although it is unclear why gender distribution of our patients showed more women than men (12 versus 1) (19)(20)(21)(22)(23), those with short bowel syndrome (24,25), and those with partial gastrectomy (12,26,27). In addition, sporadic case reports also suggested that inadequate diet alone or genetic disorders affecting proteins of copper metabolism could cause copper deficiency (28)(29)(30), including Menkes disease and occipital horn syndrome (10) …”