Biological stratification of clinical disease courses in childhood immune thrombocytopenia

Schmidt, David E.; Heitink‐Pollé, Katja M. J.; Mertens, Bart; Porcelijn, Leendert; Kapur, Rick; Schoot, C. Ellen van der; Vidarsson, Gestur; Bom, Johanna G. van der; Bruin, Marrie C.A.; Haas, Masja de

doi:10.1111/jth.15232

Cited by 3 publications

(5 citation statements)

References 57 publications

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“…From a large, nationwide study of children with newly diagnosed ITP, we know that some clinical and laboratory characteristics are associated with response to IVIg, like a preceding infection and Fc gamma receptor profile 7 . Based on this trial a prediction score was composed that not only predicted clinical course but also was able to predict a higher likelihood of response to IVIG 18,19 . Anti glycoprotein Ib/IX antibodies have been supposed to predict a lower response rate to IVIg by some studies, 20 but this was not confirmed by others 7 .…”

Section: Case Discussionmentioning

confidence: 99%

“…7 Based on this trial a prediction score was composed that not only predicted clinical course but also was able to predict a higher likelihood of response to IVIG. 18,19 Anti glycoprotein Ib/IX antibodies have been supposed to predict a lower response rate to IVIg by some studies, 20 but this was not confirmed by others. 7 Data on the prediction of response to other agents in children are very scarce, so further research is needed.…”

Section: Predicting Refractory Itpmentioning

confidence: 92%

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A proposal for new definition (s) and management approach to paediatric refractory ITP: Reflections from the Intercontinental ITP Study Group

Neunert,

Heitink‐Polle,

Lambert

2023

Br J Haematol

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SummaryImmune thrombocytopenia (ITP) in children is a relatively mild and self‐limited disorder with the majority of children demonstrating normalization of platelet count by 12 months from diagnosis. Because of this, many children with ITP can be observed without the need for treatment. When needed, treatment with either intravenous immunoglobulin (IVIG) or corticosteroids is highly effective (>80% IVIG and >95% corticosteroids). For those children who require second‐line therapies, response rates of >60% are seen with both the thrombopoietin‐receptor agonists and rituximab. Despite this, some children will have ‘refractory’ ITP (rITP) with poor or transient responses to platelet‐raising therapies. Here, we review the clinical features of rITP in children, outline proposed classifications and explore potential predictors for children with rITP.

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Section: Case Discussionmentioning

confidence: 99%

Section: Predicting Refractory Itpmentioning

confidence: 92%

A proposal for new definition (s) and management approach to paediatric refractory ITP: Reflections from the Intercontinental ITP Study Group

Neunert,

Heitink‐Polle,

Lambert

2023

Br J Haematol

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“…1 Much effort is invested in elucidating the etiology of ITP and prediction of ITP prognosis. 3 Previous results showed that oxidative stress could be involved in ITP development, similar to other diseases of autoimmune etiology. 4 Oxidative stress is usually defined as an imbalance between production and elimination of reactive oxygen and/or nitrogen species (ROS/RNS), due to increased production of ROS/RNS or/and impaired function of the antioxidative defense system.…”

Section: Introductionmentioning

confidence: 93%

“…7 Oxidative modification of proteins, such as oxidation of amino acid residues or oxidation by addition of aldehydes, may induce conformational alterations, formation of antigenic determinants, and initiation of autoantibody production. 3 Furthermore, ITP platelets have lower intracellular antioxidative capacity, and an increased level of pro-oxidants augments expression of NLRP3 inflammasome and interleukin (IL)-1β production. 8 Blockage of NLRP3, as well as caspase-1, in ITP platelets reduced production of IL-1β and pyroptosis, thus defining the ROS-NLRP3-caspase-1 signaling cascade in ITP development.…”

Section: Introductionmentioning

confidence: 99%

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

Medovic,

Srejovic,

Medovic

et al. 2023

Thromb Haemost

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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.

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“…Platelets have been observed to shed microparticles from their membrane during platelet activation and platelet apoptosis [47,48]. In ITP, a (viral) infection often precedes the onset of the disease, especially in children [58,59]. Such a preceding infection could be an initial trigger for platelets to release PMPs.…”

Section: The First Hitmentioning

confidence: 99%

Platelets in ITP: Victims in Charge of Their Own Fate?

Nelson

Jolink

Amini

et al. 2021

Cells

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Immune thrombocytopenia (ITP) is an autoimmune bleeding disorder. The pathophysiological mechanisms leading to low platelet levels in ITP have not been resolved, but at least involve autoantibody-dependent and/or cytotoxic T cell mediated platelet clearance and impaired megakaryopoiesis. In addition, T cell imbalances involving T regulatory cells (Tregs) also appear to play an important role. Intriguingly, over the past years it has become evident that platelets not only mediate hemostasis, but are able to modulate inflammatory and immunological processes upon activation. Platelets, therefore, might play an immuno-modulatory role in the pathogenesis and pathophysiology of ITP. In this respect, we propose several possible pathways in which platelets themselves may participate in the immune response in ITP. First, we will elaborate on how platelets might directly promote inflammation or stimulate immune responses in ITP. Second, we will discuss two ways in which platelet microparticles (PMPs) might contribute to the disrupted immune balance and impaired thrombopoiesis by megakaryocytes in ITP. Importantly, from these insights, new starting points for further research and for the design of potential future therapies for ITP can be envisioned.

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Biological stratification of clinical disease courses in childhood immune thrombocytopenia

Abstract: This is an open access article under the terms of the Creative Commons Attribution-NonCommercial License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited and is not used for commercial purposes.

Cited by 3 publications

References 57 publications

A proposal for new definition (s) and management approach to paediatric refractory ITP: Reflections from the Intercontinental ITP Study Group

A proposal for new definition (s) and management approach to paediatric refractory ITP: Reflections from the Intercontinental ITP Study Group

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

Platelets in ITP: Victims in Charge of Their Own Fate?

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