Download PDF
Thromb Haemost 2023; 123(12): 1129-1139
DOI: 10.1055/s-0043-1772683
Cellular Haemostasis and Platelets

Variations of Redox Balance in Different Stages of Childhood Immune Thrombocytopenic Purpura

Rasa H. Medovic 
1   Department of Pediatrics, Faculty of Medical Sciences, University of Kragujevac, Kragujevac, Serbia
2   University Clinical Center Kragujevac, Kragujevac, Serbia
,
Ivan M. Srejovic 
3   Department of Physiology, Faculty of Medical Sciences, University of Kragujevac, Kragujevac, Serbia
4   Center of Excellence for the Study of Redox Balance in Cardiovascular and Metabolic Disorders, University of Kragujevac, Kragujevac, Serbia
5   Department of Pharmacology, First Moscow State Medical University I.M. Sechenov, Moscow, Russian Federation
,
Marija V. Medovic 
2   University Clinical Center Kragujevac, Kragujevac, Serbia
6   Department of Dermatovenerology, Faculty of Medical Sciences, University of Kragujevac, Kragujevac, Serbia
,
Isidora M. Milosavljevic 
4   Center of Excellence for the Study of Redox Balance in Cardiovascular and Metabolic Disorders, University of Kragujevac, Kragujevac, Serbia
7   Department of Pharmacy, Faculty of Medical Sciences, University of Kragujevac, Kragujevac, Serbia
,
Marina R. Nikolic 
3   Department of Physiology, Faculty of Medical Sciences, University of Kragujevac, Kragujevac, Serbia
4   Center of Excellence for the Study of Redox Balance in Cardiovascular and Metabolic Disorders, University of Kragujevac, Kragujevac, Serbia
,
Aleksandra Z. Stojanovic 
4   Center of Excellence for the Study of Redox Balance in Cardiovascular and Metabolic Disorders, University of Kragujevac, Kragujevac, Serbia
7   Department of Pharmacy, Faculty of Medical Sciences, University of Kragujevac, Kragujevac, Serbia
,
Milos B. Kuzmanovic
8   Mother and Child Health Institute of Serbia “Dr Vukan Cupic”, Belgrade, Serbia
9   Department of Pediatrics, Medical Faculty, University of Belgrade, Belgrade, Serbia
,
Predrag M. Djurdjevic 
2   University Clinical Center Kragujevac, Kragujevac, Serbia
10   Department of Internal medicine, Faculty of Medical Sciences, University of Kragujevac, Kragujevac, Serbia
,
Sergey B. Bolevich 
11   Department of Human Pathology, First Moscow State Medical University I.M. Sechenov, Moscow, Russia Federation
,
Vladimir P. Fisenko 
5   Department of Pharmacology, First Moscow State Medical University I.M. Sechenov, Moscow, Russian Federation
,
Vladimir Lj. Jakovljevic 
3   Department of Physiology, Faculty of Medical Sciences, University of Kragujevac, Kragujevac, Serbia
4   Center of Excellence for the Study of Redox Balance in Cardiovascular and Metabolic Disorders, University of Kragujevac, Kragujevac, Serbia
11   Department of Human Pathology, First Moscow State Medical University I.M. Sechenov, Moscow, Russia Federation
,
Zoran R. Igrutinovic 
1   Department of Pediatrics, Faculty of Medical Sciences, University of Kragujevac, Kragujevac, Serbia
2   University Clinical Center Kragujevac, Kragujevac, Serbia
› Author Affiliations Funding The project was supported by Faculty of Medical Sciences, University of Kragujevac (JP 27/20) and Ministry of Science, Technical Development and Innovation of the Republic of Serbia (contract No. 451-03-47/2023-01/200111).
› Further Information
Also available at
    Permissions and Reprints


Abstract

Background Few previous studies indicated the role of oxidative stress in the pathogenesis of childhood idiopathic thrombocytopenic purpura (ITP), but there are little data regarding changes in redox balance in different forms of the disease, and changes after therapeutic procedures. We aimed to investigate the values of pro-oxidants and antioxidative capacity in various forms of ITP before and after the applying therapy.

Materials and Methods The research included 102 children, classified into the following groups: (1) newly diagnosed ITP (ndITP), (2) persistent ITP, (3) chronic ITP (chITP), and (4) control groups: (A) healthy control and (B) previously experienced ITP—healthy children who had been suffering from ITP earlier. During the clinical assessment, a blood sample was taken from the patients, from which the value of pro-oxidants (index of lipid peroxidation measured as TBARS, nitrites [NO2 −], as measurement of nitric oxide [NO] production, superoxide anion radical [O2 −], and hydrogen peroxide [H2O2]) and the capacity of antioxidant protection (activity of superoxide dismutase and catalase, and quantity of reduced glutathione) were determined spectrophotometrically.

Results Our results demonstrated that values of pro-oxidants, especially reflected through the TBARS and O2 −, were the highest in the ndITP and exacerbated chITP groups. Also, the activity of the endogenous antioxidative defense system was the lowest in these groups. Intravenous immunoglobulin therapy in the ndITP group exerted the most prominent effect on the redox balance.

Conclusion It can be concluded that severity and exacerbation of the ITP are closely related to the redox status.

Keywords

childhood idiopathic thrombocytopenic purpura - corticosteroids - endogenous antioxidant - intravenous immunoglobulins - oxidative stress

Ethical Approval Statement

Parents and patients were informed about the research, and written consent was obtained from the parents, and from the patients themselves if they were older than 12 years, to participate in the research. Ethical approval was obtained from University Clinical Center Kragujevac, Kragujevac, Serbia (approval number 01-22-656).


Authors' Contribution

Conception and design of the study: R.H.M., Z.R.I., I.M.S., V.L.J.; acquisition of data: R.H.M., M.B.K., P.M.D., Z.R.I.; analysis and interpretation of data: R.H.M., I.M.S., M.V.M, I.M.M., M.R.N., A.Z.S., S.B.B., V.P.F.; drafting the article: R.H.M., I.M.S., V.L.J., A.Z.S. All authors approved the final version of the manuscript before submission.




Publication History

Received: 18 January 2023

Accepted: 02 June 2023

Article published online:
21 August 2023

© 2023. Thieme. All rights reserved.

Georg Thieme Verlag KG
Rüdigerstraße 14, 70469 Stuttgart, Germany

 

  • References

  • 1 Schmidt DE, Heitink-Polle KMJ, Porcelijn L. et al. Anti-platelet antibodies in childhood immune thrombocytopenia: prevalence and prognostic implications. J Thromb Haemost 2020; 18 (05) 1210-1220
    CrossrefPubMedGoogle Scholar
  • 2 Rodeghiero F, Stasi R, Gernsheimer T. et al. Standardization of terminology, definitions and outcome criteria in immune thrombocytopenic purpura of adults and children: report from an international working group. Blood 2009; 113 (11) 2386-2393
    CrossrefPubMedGoogle Scholar
  • 3 Schmidt DE, Heitink-Pollé KMJ, Mertens B. et al. Biological stratification of clinical disease courses in childhood immune thrombocytopenia. J Thromb Haemost 2021; 19 (04) 1071-1081
    CrossrefPubMedGoogle Scholar
  • 4 Zhang B, Zehnder JL. Oxidative stress and immune thrombocytopenia. Semin Hematol 2013; 50 (03) e1-e4
    CrossrefPubMedGoogle Scholar
  • 5 Elalfy MS, Elhenawy YI, Deifalla S, Hegazy M, Sabra A, Abdelaziz Y. Oxidant/antioxidant status in children and adolescents with immune thrombocytopenia (ITP) and the role of an adjuvant antioxidant therapy. Pediatr Blood Cancer 2015; 62 (05) 830-837
    CrossrefPubMedGoogle Scholar
  • 6 Zhang B, Lo C, Shen L. et al. The role of vanin-1 and oxidative stress-related pathways in distinguishing acute and chronic pediatric ITP. Blood 2011; 117 (17) 4569-4579
    CrossrefPubMedGoogle Scholar
  • 7 Kamhieh-Milz J, Salama A. Oxidative stress is predominant in female but not in male patients with autoimmune thrombocytopenia. Oxid Med Cell Longev 2014; 2014: 720347
    CrossrefPubMedGoogle Scholar
  • 8 Wang S, Liu Y, Li G, Feng Q, Hou M, Peng J. Reduced intracellular antioxidant capacity in platelets contributes to primary immune thrombocytopenia via ROS-NLRP3-caspase-1 pathway. Thromb Res 2021; 199: 1-9
    CrossrefPubMedGoogle Scholar
  • 9 Guo NH, Fu X, Zi FM, Song Y, Wang S, Cheng J. The potential therapeutic benefit of resveratrol on Th17/Treg imbalance in immune thrombocytopenic purpura. Int Immunopharmacol 2019; 73: 181-192
    CrossrefPubMedGoogle Scholar
  • 10 Buchanan GR, Adix L. Grading of hemorrhage in children with idiopathic thrombocytopenic purpura. J Pediatr 2002; 141 (05) 683-688
    CrossrefPubMedGoogle Scholar
  • 11 Al-Samkari H, Cronin A, Arnold DM, Rodeghiero F, Grace RF. Extensive variability in platelet, bleeding, and QOL outcome measures in adult and pediatric ITP: communication from the ISTH SSC subcommittee on platelet immunology. J Thromb Haemost 2021; 19 (09) 2348-2354
    CrossrefPubMedGoogle Scholar
  • 12 Joksimovic Jovic J, Antic S, Nikolic T. et al. Erythropoietin resistance development in hemodialysis patients: the role of oxidative stress. Oxid Med Cell Longev 2022; 2022: 9598211
    CrossrefPubMedGoogle Scholar
  • 13 Milosavljevic I, Jakovljevic V, Petrovic D. et al. Standardized Aronia melanocarpa extract regulates redox status in patients receiving hemodialysis with anemia. Mol Cell Biochem 2021; 476 (11) 4167-4175
    CrossrefPubMedGoogle Scholar
  • 14 Stojanovic A, Veselinovic M, Draginic N. et al. The influence of menopause and inflammation on redox status and bone mineral density in patients with rheumatoid arthritis. Oxid Med Cell Longev 2021; 2021: 9458587
    CrossrefPubMedGoogle Scholar
  • 15 Misra HP, Fridovich I. The role of superoxide anion in the autoxidation of epinephrine and a simple assay for superoxide dismutase. J Biol Chem 1972; 247 (10) 3170-3175
    CrossrefPubMedGoogle Scholar
  • 16 Bissinger R, Bhuyan AAM, Qadri SM, Lang F. Oxidative stress, eryptosis and anemia: a pivotal mechanistic nexus in systemic diseases. FEBS J 2019; 286 (05) 826-854
    CrossrefPubMedGoogle Scholar
  • 17 Liang Y, Zhou R, Liu X. et al. Leukemia inhibitory factor facilitates self-renewal and differentiation and attenuates oxidative stress of BMSCs by activating PI3K/AKT signaling. Oxid Med Cell Longev 2022; 2022: 5772509
    CrossrefPubMedGoogle Scholar
  • 18 Xiong S, Chng WJ, Zhou J. Crosstalk between endoplasmic reticulum stress and oxidative stress: a dynamic duo in multiple myeloma. Cell Mol Life Sci 2021; 78 (08) 3883-3906
    CrossrefPubMedGoogle Scholar
  • 19 Jafri F, Seong G, Jang T. et al. L-glutamine for sickle cell disease: more than reducing redox. Ann Hematol 2022; 101 (08) 1645-1654
    CrossrefPubMedGoogle Scholar
  • 20 Hirsch RE, Sibmooh N, Fucharoen S, Friedman JM. HbE/β-thalassemia and oxidative stress: the key to pathophysiological mechanisms and novel therapeutics. Antioxid Redox Signal 2017; 26 (14) 794-813
    CrossrefPubMedGoogle Scholar
  • 21 Voskou S, Aslan M, Fanis P, Phylactides M, Kleanthous M. Oxidative stress in β-thalassaemia and sickle cell disease. Redox Biol 2015; 6: 226-239
    CrossrefPubMedGoogle Scholar
  • 22 Beyazit H, Demiryürek AT, Temel MT, Pekpak E, Demiryürek S, Akbayram S. Investigation of dynamic thiol/disulfide homeostasis in children with acute immune thrombocytopenia. J Pediatr Hematol Oncol 2019; 41 (06) 463-467
    CrossrefPubMedGoogle Scholar
  • 23 Semple JW, Provan D. The immunopathogenesis of immune thrombocytopenia: T cells still take center-stage. Curr Opin Hematol 2012; 19 (05) 357-362
    CrossrefPubMedGoogle Scholar
  • 24 Akbayram S, Doğan M, Akgün C. et al. The association of oxidant status and antioxidant capacity in children with acute and chronic ITP. J Pediatr Hematol Oncol 2010; 32 (04) 277-281
    CrossrefPubMedGoogle Scholar
  • 25 Jin CQ, Dong HX, Cheng PP, Zhou JW, Zheng BY, Liu F. Antioxidant status and oxidative stress in patients with chronic ITP. Scand J Immunol 2013; 77 (06) 482-487
    CrossrefPubMedGoogle Scholar
  • 26 Kamhieh-Milz J, Bal G, Sterzer V, Kamhieh-Milz S, Arbach O, Salama A. Reduced antioxidant capacities in platelets from patients with autoimmune thrombocytopenia purpura (ITP). Platelets 2012; 23 (03) 184-194
    CrossrefPubMedGoogle Scholar
  • 27 Nelson VS, Jolink AC, Amini SN. et al. Platelets in ITP: victims in charge of their own fate?. Cells 2021; 10 (11) 3235
    CrossrefPubMedGoogle Scholar
  • 28 Ramani S, Pathak A, Dalal V, Paul A, Biswas S. Oxidative stress in autoimmune diseases: an under dealt malice. Curr Protein Pept Sci 2020; 21 (06) 611-621
    CrossrefPubMedGoogle Scholar
  • 29 Schwab I, Nimmerjahn F. Intravenous immunoglobulin therapy: how does IgG modulate the immune system?. Nat Rev Immunol 2013; 13 (03) 176-189
    CrossrefPubMedGoogle Scholar
  • 30 Zuercher AW, Spirig R, Baz Morelli A, Käsermann F. IVIG in autoimmune disease - potential next generation biologics. Autoimmun Rev 2016; 15 (08) 781-785
    CrossrefPubMedGoogle Scholar
  • 31 Counts SE, Ray B, Mufson EJ, Perez SE, He B, Lahiri DK. Intravenous immunoglobulin (IVIG) treatment exerts antioxidant and neuropreservatory effects in preclinical models of Alzheimer's disease. J Clin Immunol 2014; 34 Suppl 1 (0 1) S80-S85
    CrossrefPubMedGoogle Scholar
  • 32 Chen H, Souayah N. Immunoglobulins reduced oxidative stress in human microglial cells induced by high dose of acetoacetate. Brain Res 2020; 1748: 147054
    CrossrefPubMedGoogle Scholar
  • 33 Cura M, Koç A, Aksoy N, Özdemir ZC. Effect of short-term, high-dose methylprednisolone on oxidative stress in children with acute immune thrombocytopenia. Blood Res 2016; 51 (04) 261-267
    CrossrefPubMedGoogle Scholar
  • 34 Zhu Y, Dong Y, Wu L, Deng F. Changes of inflammatory mediators and oxidative stress indicators in children with Henoch-Schönlein purpura and clinical effects of hemoperfusion in the treatment of severe Henoch-Schönlein purpura with gastrointestinal involvement in children. BMC Pediatr 2019; 19 (01) 409
    CrossrefPubMedGoogle Scholar
  • 35 Heijink I, van Oosterhout A, Kliphuis N. et al. Oxidant-induced corticosteroid unresponsiveness in human bronchial epithelial cells. Thorax 2014; 69 (01) 5-13
    CrossrefPubMedGoogle Scholar
  • 36 Ito M, Yagasaki H, Kanezawa K, Shimozawa K, Hirai M, Morioka I. Incidence and outcomes of refractory immune thrombocytopenic purpura in children: a retrospective study in a single institution. Sci Rep 2021; 11 (01) 14263
    CrossrefPubMedGoogle Scholar
  • 37 Güngör T, Arman Bilir Ö, Koşan Çulha V. et al. Retrospective evaluation of children with immune thrombocytopenic purpura and factors contributing to chronicity. Pediatr Neonatol 2019; 60 (04) 411-416
    CrossrefPubMedGoogle Scholar
  • 38 Navidhamidi M, Nazari A, Dehghan S, Ebrahimpour A, Nasrnezhad R, Pourabdolhossein F. Therapeutic potential of combined therapy of vitamin A and vitamin C in the experimental autoimmune encephalomyelitis (EAE) in Lewis rats. Mol Neurobiol 2022; 59 (04) 2328-2347
    CrossrefPubMedGoogle Scholar
  • 39 Mannucci C, Casciaro M, Sorbara EE. et al. Nutraceuticals against oxidative stress in autoimmune disorders. Antioxidants 2021; 10 (02) 261
    CrossrefPubMedGoogle Scholar