Copper Deficiency and Cytopenia: A Systematic Review

Copper Deficiency and Cytopenia: A Systematic Review

Prakash Kharel, Karthik Gnanapandithan, Ramesh Kumar Pandey, Samir Jha, Alyssa Grimshaw, Smith Giri

Introduction: Copper deficiency is rare in humans unless there is a condition that affects either copper uptake or metabolism, or dietary deficiency. However, the incidence appears to be rising due to increasing gastric bypass surgery and total parenteral nutrition (TPN) use. Published data on hematological manifestations due to copper deficiency are limited to case reports, case series and small retrospective studies, creating confusion among clinicians and hematologists. We performed a systematic review of all published case reports and series to characterize hematological manifestations associated copper deficiency with a focus on risk factors, clinical manifestations, treatments and outcomes.

Methods:

Using a combination of free text and controlled vocabulary, a systematic search of the electronic literature using MEDLINE and EMBASE for published material from inception to March 2019 was performed. Two authors independently screened the titles, abstracts, and the full text of the selected papers. Subsequently, the full text of each article was assessed for eligibility and details. From the 97 reports, we included 116 cases in which the clinical course, management and outcomes were described.

Results: Of 5374 articles screened, a total of 268 articles were selected for full text review and a total of 97 reports describing 116 cases met our eligibility criteria. The median age at the time of presentation was 44 (interquartile range (IQR) 25-57) year, and 64 (55%) were males. Total of 37(32 %) had coexisting neurological symptoms. The median Hb was 7.7 gm/dl (IQR 6.2-9.5) and median WBC 2.3 (1.6-3.1). 94 (81%) of the patients had hemoglobin (Hb)< 10, 41(35%) had severe anemia Hb <7 at presentation. 80(69%) had leukopenia with white blood cell (WBC) <4K, of them only one patient had lymphopenia (1.28%), rest had neutropenia (98.72 %). Nearly half of these patients had macrocytic anemia (38, 55%) and only 3 cases had microcytic anemia. Of 78 patients with available data, 23(29%) had low platelet counts and 8 (10 %) had elevated platelet count. Zinc excess was implicated in almost half of these cases (39/87, 45%) and total parenteral nutrition (TPN) in 9 out of 87 cases (10%)

Conclusion:

Copper deficiency should be one of the reflexes in evaluation of patient who is at risk of copper deficiency specially as there is rise of bariatric surgery, survivors of significant bowel surgery patient requiring total parenteral nutrition or jejunal feed along with the baby boomers who will be the high number of patients using dentures and patient on zinc supplementation. There should always be a high degree of suspicion among clinicians when dealing with at-risk individuals to prevent irreversible complications and morbidity.