key: cord-0855211-b7a883p6
authors: Abusabeib, Alyaa; El Ansari, Walid; Elhag, Wahiba
title: First Case Report of Acquired Copper Deficiency Following Revisional Single Anastomosis Duodeno-Ileal Bypass with Sleeve Gastrectomy (SADI-S) Leading to Severe Pancytopenia with Refractory Anemia
date: 2020-08-28
journal: Obes Surg
DOI: 10.1007/s11695-020-04916-3
sha: 1e2d77c216b2bd56293ac47f1d1a3221c285c26b
doc_id: 855211
cord_uid: b7a883p6

nan

Published reports of the malnutrition outcomes after SADI-S are extremely rare [9] . An exception is a study of 97 SADI-S patients, where 12% developed copper deficiency at 1 year and 11% at 3 years post-op [10] . We report a case of severe copper deficiency after revisional SADI-S leading to severe pancytopenia with cellular atypia. To the best of our knowledge, this could be the first case report of severe copper deficiency leading to profound hematological abnormalities post-SADI-S. Figure 1 depicts the sequence of events over 7 years.

A 37-year-old Qatari female presented to our outpatient bariatric clinic (Hamad General Hospital, largest tertiary care institution in Qatar) with a 4-month complaint of generalized fatigability and progressive bilateral lower limbs swelling with occasional numbness of the distal aspects of the lower limbs but no weakness. Her complaints had worsened over time, and were affecting her quality of life and ability to work. She also had frequent episodes of palpitations, exertional shortness of breath, but no chest pain. There was no nausea or vomiting, but she indicated that there was an increase in her bowel motions which had become more greasy. She denied bloody stools abdominal pain, change in appetite, fever, joint pain, or skin changes. She also complained of occasional headaches but no visual changes. Past medical history was remarkable for T2DM controlled with oral hypoglycemic agents (sitagliptin 50 mg and metformin 1000) and basal insulin, hypertension controlled by antihypertensives (valsartan 160 mg and hydrochlorothiazide 12.5 mg), bronchial asthma with recurrent exacerbations, primary infertility, and severe obesity.

The patient had undertaken laparoscopic sleeve gastrectomy (LSG) on April 2013 (Fig. 1A) as her weight then was 162 kg (BMI 57 kg/m 2 ). After the LSG, her minimum postoperative weight was 90 kg, the T2DM and hypertension resolved within the first year post-operatively and she was off medications for both conditions. Moreover, her asthma exacerbations became minimal. Weight regain started on the second year post-LSG until she reached 118 kg (BMI 42 kg/m 2 ). Hence, 3 years after her initial LSG, in December 2016, she underwent revisional laparoscopic SADI-S. Eleven months after the SADI-S (November 2017), she presented to our bariatric surgery clinic with the abovementioned complaints, claimed to be adherent to the multivitamin with minerals daily tablets and iron supplements, and denied smoking or alcohol consumption.

Upon examination, she appeared vitally stable, weighed 93.6 kg (BMI 35.6 kg/m 2 ), with normal cardiovascular, chest, and abdominal examinations, and no neurological deficits. She appeared pale and had significant bilateral lower limb edema (Grade 3), and was admitted for inpatient assessment and further management.

Laboratory results upon admission showed microcytic hypochromic anemia, leucopenia, thrombocytopenia, hypoalbuminemia, and high level of vitamin B 12 (Fig. 1C) . She was started on IV multivitamins and trace elements, thiamine IV, and highprotein diet, and eventually required total parental nutrition until laboratory results became available. Peripheral blood smear confirmed pancytopenia with cellular atypia (Fig. 1C) . Further investigations revealed low ceruloplasmin, and severe deficiencies of copper, zinc, selenium, vitamin D, and folate but normal cholesterol and lipid profile (Fig. 1C) . Hemoglobin electrophoresis showed normal hemoglobin pattern.

For the severe microcytic hypochromic anemia, she received a transfusion of two units of packed red blood cells (Fig. 1D ) that resulted in a transient rise in hematocrit count and hemoglobin level (Fig. 1E ), followed by a gradual drop of both levels over the following days (Fig. 1F) . The pancytopenia progressively improved following the initiation of an additional 0.5 mg of copper chloride IV daily dose after diagnosis of copper deficiency.

Screening for celiac disease was negative and esophagogastroduodenoscopy was normal. She was hospitalized for 2 weeks. At discharge, her blood picture was improving (Fig. 1G) . She was prescribed multivitamin and minerals daily tablet, copper gluconate 2 mg daily, selenium 200 mcg bid, vitamin D, calcium and iron supplements, cyanocobalamin 1 mg daily, pancreatic enzymes for suspected pancreatic insufficiency, and high-protein supplement. At follow-up, 2 weeks after discharge, her laboratory results showed a normal level of serum copper, resolution of the leukopenia, neutropenia, and thrombocytopenia, and improvement of microcytic hypochromic anemia (Fig. 1H) . She reported significant improvements in her symptoms and better quality of life.

We report a case report of severe copper deficiency leading to hematological abnormalities post-SADI-S. The mechanism/s by which copper deficiency causes anemia are multifactorial. Copper and iron interact through ceruloplasmin, a copperdependent oxidase that helps to transport iron into the plasma along with transferrin [11] . In addition, hephaestin, a transmembrane copper containing ferroxidase, helps to export iron from enterocytes into the blood circulation, and as copper is essential to mobilize iron from the liver to the bone marrow where it is consumed, thus copper significantly affects erythropoiesis [11] . These mechanisms and interactions explain how the laboratory findings of copper deficiency and myelodysplastic syndromes mimic each other [11, 12] . Our patient had anemia and leucopenia (mainly neutropenia), in agreement with myelodysplastic syndrome [11, 12] . In addition, she had moderate thrombocytopenia which is less frequently reported in copper deficiency [4] .

The patient underwent LSG as a primary weight loss surgery followed by SADI-S as revisional surgery. Weight loss surgery that is characterized by combined restrictive and malabsorptive effects alters copper absorption in the stomach, duodenum, and ilium [13] . In addition, other factors e.g. pre-operative deficiencies, post-surgery food intolerance, changes in taste and eating patterns, and non-adherence to dietary and supplement recommendations could collectively lead to copper deficiency. The literature completely lacks case reports outlining the types and levels of the range of micro-and macronutrient deficiencies after SADI-S. However, copper deficiency has been reported following mainly malabsorptive procedures, e.g., gastric bypass surgery [14, 15] , and less frequently after sleeve gastrectomy and duodenal switch [16, 17] .

While the neurological examination of our patient was normal, she mentioned a history of occasional episodes of lower limb numbness that might be attributed to the copper deficiency, given that her laboratory results showed normal thiamine and vitamin B 12 blood levels. Various myelopathies and peripheral neuropathies have been reported with copper deficiency, some of which were severe and irreversible [3, 4, 18, 19] . In addition, although copper deficiency has been observed as a possible cause of ischemic heart disease by significantly promoting major risk factors such as hypercholesterolemia, chronic inflammation, oxidative stress, and glucose intolerance [20] , our patient had normal cholesterol and lipid profiles.

Refractory iron deficiency anemia with copper deficiency has been described post-duodenal switch surgery [21] . In our case, the two units of packed red blood cells transfusion resulted in a transient rise in hematocrit count and hemoglobin level (Fig. 1E) , followed by a gradual dropping of both, highlighting that among anemic patients, copper deficiency could cause a refractory response to blood transfusion and iron replacement. Hence, prompt diagnosis and treatment of copper deficiency could help to prevent serious complications such as severe pancytopenia with its consequences and neuropathy. Finally, although the patient also had concomitant folate deficiency, however, her peripheral smear showed hypochromic microcytic anemia (as opposed to the macrocytic anemia observed with folate deficiency), suggesting that among post-bariatric surgery patients with concomitant hypocuperimia, that the effects of the copper deficiency on erythropoiesis could be more pronounced than that of the folate.

Although rare, the current case emphasizes that the bariatric team should be aware that after bariatric procedures such as SADI-S, micronutrient deficiencies could be encountered. In order to avoid complications, early diagnosis, and prompt treatment of copper and other micronutrient deficiencies are critical. Mild neurological symptoms among post-bariatric surgery patients should alert the bariatric team to possible micronutrient/copper deficiency. Findings of anemia, pancytopenia, and cellular atypia warrant extensive assessment and replacement of micronutrients.

Acknowledgments The authors appreciate the willingness of the patient to agree to this case report.

Conflict of Interest The authors declare that they have no conflicts of interest.

Ethical Approval Statement All procedures performed in the study involving human participant were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards. This case report has been approved by the Medical Research center (IRB) at Hamad Medical Corporation (approval # MRC-04-20-618).

Informed Consent Statement Due to the COVID-19 pandemic, written informed consent was not possible as it was deemed unethical that the patient travels to the hospital to sign the consent. Hence, informed verbal consent was obtained over the telephone from the patient after a through explanation of the fact that her case will be published in a scientific journal without breaking her confidentiality or disclosing her identity and she happily agreed to do so; the discussion was witnessed by a coauthor.

Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/.

Pancytopenia complicated with peripheral neuropathy due to copper deficiency: clinical diagnostic review

MON-595 Severe copper deficiency post-bariatric surgery with serious preventable complications

Anemia from A to zinc: hypocupremia in the setting of gastric bypass and zinc excess

Copper deficiency (hypocupremia) and pancytopenia late after gastric bypass surgery

Bariatric surgery and long-term nutritional issues

Singleanastomosis duodenoileal bypass with sleeve gastrectomy (SADI-S) for obese diabetic patients

Technical options for malabsorption issues after single anastomosis duodenoileal bypass with sleeve gastrectomy

Progressive myeloneuropathy with symptomatic anaemia

The single anastomosis duodenal switch modifications: a review of the current literature on outcomes

Copper: effects of deficiency and overload. Interrelations between essential metal ions and human diseases

Copper deficiency mimicking myelodysplastic syndrome

Myelodysplastic syndromes: moving towards personalized management

Single-anastomosis duodeno-ileal -new revision procedure in a patient with insufficient weight loss after sleeve gastrectomy

Acquired copper deficiency: a potentially serious and preventable complication following gastric bypass surgery

Incidence and prevalence of copper deficiency following Roux-en-Y gastric bypass surgery

Paralysis due to thiamine and copper deficiencies following sleeve gastrectomy complicated by oral intolerance with recurrent pancreatitis

Neurologic dysfunction and pancytopenia secondary to acquired copper deficiency following duodenal switch: case report and review of the literature

Copper deficiency, a new triad: anemia, leucopenia, and myeloneuropathy

Copper deficiency myelopathy: a report of two cases

Copper deficiency may be a leading cause of ischaemic heart disease

Refractory iron deficiency anemia. Current Developments in Nutrition

Publisher's Note Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations