Zinc deficiency affects half of children and adolescents with primary immune thrombocytopenia, an Egyptian cross-sectional study has found, yet the trace element disturbance showed no significant link to disease severity, chronicity, or response to treatment. The study, published in the Egyptian Pediatric Association Gazette, measured serum copper and zinc in 74 patients aged 2 to 18 years treated at Cairo University Children’s Hospital and concluded that these deficiencies may represent non-specific findings rather than determinants of clinical outcome in pediatric immune thrombocytopenia.
Primary immune thrombocytopenia, commonly abbreviated ITP, is an acquired autoimmune hematological disorder characterized by isolated thrombocytopenia, defined as a platelet count below 100 × 10⁹ per liter, together with an increased risk of bleeding. Diagnosis requires careful exclusion of other causes of thrombocytopenia, including systemic autoimmune disease, infection, and medication effects, supported by clinical evaluation and laboratory findings. Most pediatric cases are acute and self-limiting, but the study’s authors note that approximately 20 to 25 percent of children evolve into a chronic form persisting beyond twelve months. Chronic ITP poses a substantial clinical challenge because patients may experience recurrent bleeding episodes, diminished quality of life, and refractoriness to standard therapies such as corticosteroids and intravenous immunoglobulin.
The rationale for examining trace elements rests on oxidative stress, which accumulating evidence identifies as one contributor to ITP pathogenesis. Oxidative stress is thought to trigger the production of autoantibodies targeting platelets. Copper and zinc form part of the body’s physiological antioxidant defenses: both are cofactors of two isoenzymes of the superoxide dismutase system, the cytoplasmic SOD1 and the extracellular SOD3. In deficiency states, the activity of these enzymes decreases and oxidative stress increases. Zinc additionally inhibits the pro-oxidant enzyme NADPH oxidase, preventing superoxide formation and helping to protect cells against oxidative damage, while copper is an integral component of ceruloplasmin, an antioxidant ferroxidase with anti-inflammatory effects. Because copper and zinc deficiencies are common nutritional problems that can be treated medically, the researchers asked whether subnormal levels might influence disease course.
The cross-sectional study enrolled 74 children and adolescents diagnosed with primary ITP according to international consensus guidelines, all registered and followed at the Hematology Outpatient Clinic of Cairo University Children’s Hospital between May 2025 and December 2025. Patients with congenital bone marrow failure syndromes, myelodysplastic syndromes, or platelet dysfunction were excluded. Participants underwent bone marrow aspiration after failure of first-line therapy and before starting second-line treatment with a thrombopoietin receptor agonist; marrow examination consistently revealed preserved platelet production with hypercellular marrow in all cases. The cohort comprised 41 males (55.4 percent) and 33 females (44.6 percent), a male-to-female ratio of 1.24 to 1.
Clinical assessment used the ITP-specific bleeding scale based on the ISTH Scientific and Standardization Committee Bleeding Assessment Tool, and disease status was classified as persistent, lasting three to twelve months, in 12 patients (16.2 percent), or chronic, lasting more than twelve months, in 62 patients (83.8 percent). Response to therapy was graded under National Institutes of Health guidelines: 62 patients were classified as responders, having achieved either a complete response, defined as a platelet count of at least 100 × 10⁹ per liter without bleeding, or a response, defined as a platelet count of at least 30 × 10⁹ per liter with at least a twofold increase from baseline and no bleeding. The remaining 12 patients were non-responders. Serum zinc and copper concentrations were measured by atomic absorption spectrophotometry on a PerkinElmer AAS 800 instrument, with samples diluted 1:4 in distilled water and concentrations calculated against calibration curves from standard solutions.
The cohort’s mean age was 8.07 ± 3.24 years, and disease duration ranged from four months to eight years with a median of two years. Bleeding manifestations were the predominant presenting feature, occurring in 73 percent of patients. At enrollment, 27 percent had no bleeding, 31.1 percent showed scattered ecchymoses or petechiae, and 41.9 percent reported recurrent bleeding episodes. Most patients, 58 cases or 78.4 percent, received steroids as first-line treatment, while combined intravenous immunoglobulin and steroids were used in 16 cases (21.6 percent). On current therapy, 78.3 percent had started eltrombopag, 6.8 percent were on romiplostim, and 14.9 percent were off treatment. Complete response had been achieved in 48.6 percent of patients, partial response in 35.1 percent, and no response in 16.2 percent.
The central laboratory finding was a stark imbalance between the two trace elements. Zinc deficiency, defined as a serum level below 50 µg/dL, was present in 50 percent of the cohort, 37 of 74 patients. Serum zinc values ranged from 23.60 to 86.10 µg/dL, with a mean of 51.62 ± 15.67 µg/dL and a median of 50.55. Copper deficiency, by contrast, was detected in only 9.5 percent, seven patients, with serum copper ranging from 62.6 to 201.3 µg/dL. When the researchers split the cohort into zinc-deficient and zinc-normal groups of 37 patients each, they found no significant differences in age, sex, platelet count on the day of sampling, or response to treatment. Zinc deficiency was somewhat more frequent among females, 54.1 percent versus 45.9 percent in males, but this did not reach statistical significance. Platelet counts tended to be lower in zinc-deficient patients without statistical significance, and a higher proportion of zinc-normal children were off treatment, 25 percent versus 5 percent, a difference of only marginal significance. Subnormal copper levels were also more common in the zinc-deficient group, 16.2 percent versus 2.7 percent, again without statistical significance.
Correlation and subgroup analyses reinforced the picture of independence between trace element status and clinical course. Serum zinc levels showed no correlation with the demographic and clinical variables studied and appeared largely independent of them. Zinc deficiency was only slightly more frequent among non-responders than responders, 58.3 percent versus 48.4 percent, a non-significant difference. For copper, the seven deficient patients showed no significant differences from the 67 copper-normal patients, and serum copper showed no significant association with response quality. The sole statistically significant correlation was a weak negative association between serum copper and age. The authors contrasted their findings with a Turkish study of 154 individuals, predominantly adults, in which copper deficiency was observed in 7.8 percent of cases, closely matching their figure, but zinc deficiency was identified in only 3.9 percent, far below the 50 percent seen in this pediatric cohort. That discrepancy, the authors suggest, may reflect age-related differences in nutritional status, developmental physiology, and environmental exposures, indicating that pediatric and adult populations may exhibit distinct vulnerability profiles. They also note that adult studies by Sincan and colleagues reported a significant correlation between serum copper levels and response to first-line therapy, and that Chen and associates identified serum copper as a protective factor for ITP, relations their analyses failed to confirm, most likely because so few children in the cohort had copper deficiency.
The authors are careful about what these results can and cannot establish. Because SOD1 activity was not evaluated, the findings cannot demonstrate functional impairment of antioxidant defense and should be interpreted only as an association between serum trace element concentrations and pediatric immune thrombocytopenia. Several further limitations constrain interpretation: the relatively small sample size limited statistical power to detect associations between trace element status and clinical outcomes; the cross-sectional design prevents establishing any causal link between the observed deficiencies and ITP pathogenesis; and the study did not measure biomarkers such as the immature platelet fraction or thrombopoietin, which could distinguish impaired platelet production from increased peripheral destruction. The authors also note that future studies would benefit from including indicators of increased oxidation, such as total antioxidant activity, SOD1 activity, malondialdehyde levels, and the ratio of reduced to oxidized glutathione.
The study’s conclusion is measured rather than dramatic. Zinc deficiency is markedly more frequent than copper deficiency among pediatric ITP patients, occurring at a rate consistent with global estimates that nearly half the population is at risk of zinc deficiency, with prevalence expected to be particularly high in developing regions of Asia and Africa, whereas copper deficiency has been reported predominantly in children with underlying malabsorption disorders and lacks comprehensive international prevalence data. Yet neither zinc nor copper levels demonstrated a significant relationship with disease severity, chronicity, or treatment response in this cohort. The findings suggest that while micronutrient deficiencies are frequent in children with primary immune thrombocytopenia, they may not serve as independent determinants of clinical outcomes, and the authors highlight the need for further investigation into any potential contribution of zinc imbalance to immune dysregulation and platelet homeostasis before such measurements could guide care.
Subject of Research: Serum copper and zinc levels in children and adolescents with primary immune thrombocytopenia
Article Title: Serum copper and zinc status in children & adolescents with primary immune thrombocytopenia
Article References: El-Sayed, D., Abdel-Salam, A., Hamed, D., Areed, M., & Al Komy, M. (2026). Serum copper and zinc status in children & adolescents with primary immune thrombocytopenia. Egyptian Pediatric Association Gazette, 74(1), Article 120. https://doi.org/10.1186/s43054-026-00618-0
Image Credits: AI Generated
DOI: 10.1186/s43054-026-00618-0
Keywords: immune thrombocytopenia, zinc deficiency, copper deficiency, pediatric hematology, trace elements, oxidative stress, cross-sectional study, platelet count, treatment response, atomic absorption spectrophotometry, antioxidant defense, chronic ITP
News Source: Harold Sullivan. (October 29, 2026). Half of Children with Immune Thrombocytopenia Show Zinc Deficiency, Study Finds. Scienmag.
