Abordarea personalizată a purpurei trombocitopenice autoimune la copil: de la episoade acute la evoluție cronică

Introduction

Immune thrombocytopenic purpura (ITP) represents the most common cause of acquired thrombocytopenia in children, being defined by an isolated decrease in platelet count, accompanied by a variable risk of bleeding. The pathogenesis primarily involves immune-mediated destruction of platelets by specific autoantibo­dies directed against membrane glycoproteins, leading to their accelerated removal by the reticuloendothelial system, particularly in the spleen. In some cases, impaired megakaryocyte maturation also contributes to the persistence of thrombocytopenia^(1,2).

In the pediatric population, ITP typically presents with an acute onset, often preceded by a recent viral infection. This association is well-documented and supports the role of respiratory or gastrointestinal infections as potential triggers of the autoimmune response. The reported incidence rates range from 1.9 to 6.4 cases per 100,000 children annually in Europe^(3,4), being similar in North America (4.2-5.3/100,000/year)⁽⁵⁾, and slightly lower in Asia⁽⁶⁾. Children aged 2 to 5 years old are most frequently afflicted, and some cohorts have noted a slight male predominance in acute presentations⁽⁷⁾.

Although the majority of pediatric cases have a favorable outcome and remit spontaneously or with minimal treatment, approximately one quarter may progress to chronic forms lasting more than 12 months. These cases require long-term monitoring and, at times, escalated therapeutic strategies⁽⁸⁾.

In recent years, the management of ITP in children has shifted towards a more individualized approach, guided not solely by platelet count but also by the severity of symptoms, clinical context, and the overall impact on quality of life. Asymptomatic or mildly symptomatic forms can be managed through observation, whereas significant bleeding manifestations warrant treatment with intravenous immunoglobulin (IVIG) or corticosteroids. In refractory cases, second-line therapies such as thrombopoietin receptor agonists or splenectomy are validated options^(9,10).

Despite its relative frequency, systematically reported epidemiological and therapeutic data on pediatric ITP in Romania remain limited. In this context, this study aims to contribute to the characterization of clinical features, etiological context, therapeutic management, and disease evolution among children diagnosed with ITP in a Romanian university hospital, through a retrospective analysis spanning ten years.

Materials and method

This retrospective observational study was conducted within the First Pediatric Department of the Emergency County Clinical Hospital Târgu-Mureș, Romania, and aimed to evaluate the clinical characteristics, treatment options and outcomes of pediatric patients diagnosed with immune thrombocytopenic purpura. The study included hospitalizations recorded between 1 January 2015 and 1 December 2024.

All patients aged 0 to 18 years old, diagnosed with immune thrombocytopenic purpura, were included based on the available clinical and laboratory data. No exclusion criteria were applied, as case selection sought to reflect the real-world clinical experience during the study period. The diagnosis was established according to internationally accepted recommendations based on the exclusion of other causes of thrombocytopenia (clinical and laboratory-based).

For each patient, the following variables were analyzed: demographic data (age, sex), initial clinical presentation (bleeding manifestations, recent medical history), type of disease course (acute, persistent, or chronic), administered treatments, and platelet count evolution. An assessment of potential triggering etiologies such as recent viral infections or vaccinations was also included, based on information documented in the medical records.

Data were compiled in an electronic database and processed using GraphPad Prism version 9.0. Descriptive statistics (mean, median, standard deviation) were applied, and the normality of distribution was tested using the Shapiro-Wilk test. Comparisons between subgroups were performed using non-parametric tests (Kruskal-Wallis, Wilcoxon) and the Chi-square test for categorical variables.

A p-value below 0.05 was considered statistically significant. The interpretation of results focused on identifying potential associations between disease onset, therapeutic approaches, and patient evolution over time.

Results

The study included 56 pediatric patients diagnosed with immune thrombocytopenic purpura (ITP), aged between 1 and 17 years old. The mean age at diagnosis was 5.92 years old, with a notable concentration of cases in the 2-5 years old age group, which accounted for nearly half of the cohort (46.4%). Sex distribution revealed a slight male predominance (53.6%), although this difference was not statistically significant.

Most patients presented with cutaneous hemorrhagic manifestations, primarily petechiae, ecchymoses and palpable purpura, reported in over 80% of cases. Mucosal bleeding – such as epistaxis, gingival bleeding or hematuria – was documented in 57.1% of patients, while life-threatening hemorrhages were rare. General symptoms such as fatigue or mild pallor were observed only in isolated cases.

Regarding disease progression, 51.8% of patients were classified as having an acute form, 5.4% as persistent and 42.8% as chronic. Patients with a post-infectious onset were more frequently diagnosed with the acute form, whereas chronic evolution was more commonly associated with older age at onset and with the absence of a clear triggering factor.

Specific therapy was initiated in 85.7% of cases. Intravenous immunoglobulin (IVIG) was the first-line treatment in 58.9% of patients, followed by cortico­steroids in 30.3% of cases. In situations with suboptimal therapeutic response or recurrent relapses, second-line therapies were employed, including thrombopoietin receptor agonists (eltrombopag) and, in selected cases, splenectomy.

At the time of admission, the median platelet count was 11,000/mm³, with values ranging between 2000 and 42,000/mm³. A significant post-treatment increase in platelet levels was observed, with a more rapid response in acute cases and a slower, yet sustained improvement in chronic forms. By 7 to 10 days after initiating ther­apy, more than two-thirds of patients had surpassed the 100,000/mm³ threshold.

Relapses occurred in 10.7% of cases, predominantly among children under the age of 5, although this association did not reach statistical significance. Overall, the clinical outcomes were favorable: 78.6% of patients achieved complete remission, 16.1% experienced partial remission, and 5.3% exhibited a stable disease course. The treatment was well tolerated, with no major adverse events reported during the follow-up period.

Discussion

The findings of this study provide valuable insights into the clinical presentation, therapeutic approaches and outcomes of children diagnosed with immune thrombocytopenic purpura in a Romanian University hospital. The average age at diagnosis and the increased incidence in the 2-5 years old age group are consistent with international data identifying this interval as the peak incidence period for pediatric ITP^(3,6,7).

The clinical manifestations were represented predominantly by cutaneous and mucosal hemorrhages, reflecting the classic profile described in the literature. In the multicenter study conducted by Kühne et al., purpura and petechiae were reported in over 75% of children with ITP, with epistaxis and gingival bleeding being the most common mucosal hemorrhages⁽⁷⁾.

The proportion of chronic cases in our cohort (42.8%) was higher than that reported in most European studies (20-30%), possibly due to closer long-term monitoring or later presentation. According to a recent meta-analysis, chronic evolution is influenced by age at onset, absence of a clear viral trigger, and poor initial treatment response^(4,8). These elements were also observed in our cohort, where chronic forms were more frequent in patients over the age of 10 years old.

First-line treatment, consisting of intravenous immunoglobulin and corticosteroids, led to satisfactory responses in most cases, in line with current international guidelines (ASH 2019, ICR 2019)^(9,10). Neunert et al. reported that in moderate to severe symptomatic cases, these therapies result in a rapid response in over 70% of patients⁽⁹⁾. In our study, the outcomes were especially favorable in children with acute onset, while responses were slower in chronic forms, supporting the need for periodic reassessment of therapeutic strategy.

The use of thrombopoietin receptor agonists (TPO-RA), such as eltrombopag, proved effective in refractory cases in our cohort. These findings are consistent with the PETIT and PETIT2 trials, which demonstrated significant platelet increases in children with chronic ITP⁽¹¹⁾. Additionally, these agents were well tolerated, with no serious adverse effects reported, reaffirming their role in modern treatment strategies.

Although relapses were infrequent (10.7%), they occurred more commonly in children under 5 years of age – an observation echoed in other studies, possibly related to immature immune responses⁽⁶⁾. While this association was not statistically significant in our cohort, it suggests the importance of close follow-up in this age group.

Compared to other large-scale European multicenter studies that benefit from more extensive cohorts and advanced healthcare infrastructure⁽¹³⁾, the clinical profile observed in our population appeared milder, with fewer major complications. Such differences may be influenced by factors including healthcare access, timing of diagnosis, variability in symptom reporting, and treatment protocol adherence⁽¹⁴⁾. Therefore, direct comparisons between cohorts from Eastern and Western Europe should be approached with caution, considering the broader systemic and epidemiological disparities.

Overall, the results support the notion that pediatric immune thrombocytopenic purpura is a highly heterogeneous condition, but one with a generally favorable prognosis. The therapeutic management should be flexible and tailored to individual clinical profiles, while the integration of modern therapies in refractory cases can significantly improve long-term outcomes.

However, some limitations of this study should be acknowledged. Given its retrospective design, the analysis was based on previously documented data, which may have lacked certain clinical details and limited the ability to establish firm causal relationships. The relatively small sample size may also affect the extent to which the find­ings can be generalized to broader populations. Being a single-center study, the results may reflect specific insti­tu­tional practices that do not necessarily mirror national or international approaches. Additionally, limited access to advanced therapeutic options, often shaped by financial considerations, could have played a role in treatment de­ci­sions, particularly in more severe or refractory cases.

Conclusions

Pediatric immune thrombocytopenic purpura remains a clinically variable disorder with an unpredictable course. Early diagnosis and appropriate therapeutic management enable favorable outcomes in most cases. The retrospective analysis conducted in this study outlined the clinical and therapeutic characteristics of pediatric ITP, with a predominance of acute forms frequently associated with post-infectious contexts.

The overall evolution was favorable, particularly with first-line therapies. However, the substantial pro­por­tion of chronic cases underscores the need for long-term surveillance. Therapeutic individualization, adap­­ted to disease severity and treatment response, re­mains essential for optimizing management. The inte­gra­tion of modern therapies in refractory forms and the adaptation of treatment strategies to local clinical con­texts may further enhance the prognosis and the qua­li­ty of care in pediatric immune thrombocytopenic pur­pura.  

Corresponding author: Ilinca Misarăș E-mail: octaviailinca22@gmail.com

Conflict of interest: none declared.

Financial support: none declared.

This work is permanently accessible online free of charge and published under the CC-BY licence.