Thrombocytopenic Purpura In Children Research Articles

Congenital thrombotic thrombocytopenic purpura in children

Introduction. Congenital thrombotic thrombocytopenic purpura (TTP) is a rare and life-threatening genetic disorder characterized by recurrent episodes of microangiopathic hemolytic anemia, thrombocytopenia, and organ dysfunction due to the defi ciency or dysfunction of the ADAMTS13 enzyme. Despite the availability of clinical and laboratory diagnostic criteria the diagnosis remains challenging due to a wide range of diseases with similar appearance.Aim: to analyze the clinical manifestations and treatment results of identifi ed cases of congenital TTP at the Dmitry Rogachev National Medical Research Center of Pediatric Hematology, Oncology and Immunology.Methods. This article reviews 11 clinical cases with congenital TTP genetically confi rmed or with typical clinical and laboratory signs.Results. Clinical and laboratory signs of TTP are highly variable and nonspecifi c, which was observed in the described cohort of patients. One of the trigger factors is often an acute respiratory viral infection, and stabilization of the disease can occur after transfusions of blood components. A delay of diagnosis can often lead not only to a delay of correct therapy, but also to the prescription of wrong therapy. The main diagnosis confi rmatory method was a molecular genetic test, which was carried out in 8 cases. All patients diagnosed with congenital TTP were successfully treated with FFP therapy.Conclusion. Early diagnosis of TTP is diffi cult due to the lack of specifi c clinical manifestations and easily accessible laboratory tests

Predictor Factors for Chronicity in Immune Thrombocytopenic Purpura in Children.

(1) Background: Immune thrombocytopenia (ITP) is an acute autoimmune blood disorder that is the main cause of thrombocytopenia in children. It is characterized by a decrease in platelets below 100 × 109/L, and limited evolution with severe complications such as intracranial hemorrhage. The chronic form is defined by the persistence of thrombocytopenia more than 12 months after diagnosis. (2) Methods: We performed a retrospective study over a period of 10 years (1 January 2011-31 December 2020) at the Emergency Clinical Hospital for Children "Sf. Maria", Iasi. The aim of the study was to describe the clinical characteristics and to determine the prognostic factors in immune thrombocytopenia in children. (3) Results: In this study we included 271 children with ITP, comprising 123 females (45.4%) and 148 males (54.6%). The remission rate was higher in males, being 68.9% compared to 56.1% in females. Children with ITP under 9 years of age had a higher remission rate. Children with a platelet count > 10 × 109/L at diagnosis had a higher likelihood-of-remission rate compared to patients who presented initial platelet count below this value. (4) Conclusions: The risk factors highly suggestive for chronicity are: age at diagnosis, female sex, and the number of platelets at the onset of the disease.

Expert consensus on diagnosis and treatment of hereditary thrombotic thrombocytopenic purpura in children

儿童遗传性血栓性血小板减少性紫癜（hTTP）是一种少见但严重，甚至可致命的儿童血栓性微血管病，其发病机制为血管性血友病因子裂解酶（ADAMTS13）基因突变所导致的ADAMTS13活性持续严重缺乏。相较于成人，儿童期起病的hTTP更易出现脑或肾远期并发症，对预防性替代治疗的需求更迫切。本共识涵盖hTTP的定义、诊断、鉴别诊断及治疗，旨在为中国儿科医师开展儿童hTTP规范化诊治提供参考。.

The Use of Clinical Scores in the Management of Immune Thrombocytopenic Purpura in Children.

While the majority of children with recently diagnosed ITP have a benign, self-limiting condition, most often with a spontaneously recovery, 40% of children with ITP progress toward persistent ITP and 10–20% goes toward chronicity. Several clinical scores have been developed with the aim to perform a better monitoring outcome or to differentiate transient vs. persistent ITP (e.g., Donato score). Our paper aims to describe and to compare the most important scores used in the management of ITP in children: bleeding severity scores and chronicity prediction scores. These scores include a combination of different already known risk factors: age, gender, presence of a previous infections or vaccination, bleeding grade, type of onset, platelet count at diagnosis. The real utility of these scores has been a matter of debate and no consensus has been reached so far as to their necessity to be implemented as compulsory tool in the care of children with ITP.

Molecular Diagnosis Is Vital to the Accurate Classification and Management of Thrombotic Thrombocytopenic Purpura in Children.

Thrombotic thrombocytopenic purpura (TTP) is a rare but potentially life-threatening hematologic disease, presenting a myriad of diagnostic and management challenges in children. Here, we provide a review of this disorder and discuss 2 exemplary cases of TTP occurring in adolescents, emphasizing the need for consideration of late-onset congenital TTP (cTTP). We demonstrate the importance of early confirmation of ADAMTS13 enzyme deficiency and the presence or absence of ADAMTS13 inhibitor in order to rapidly initiate the appropriate life-saving therapies. Ultimately, molecular testing is paramount to distinguishing between congenital and acquired immune-mediated TTP.

Assessment of plasmablast cells in immune thrombocytopenic purpura in children

Primary immune thrombocytopenic purpura (ITP) is an autoimmune disorder with platelet destruction due to B- and T-cell dysregulation and antiplatelet autoantibodies production. Flow cytometry can be used to further characterize the B- and T-cell compartments involved in platelet destruction. This case-control study was to enumerate plasmablast cells in pediatric ITP patients and to correlate their levels with disease course. This study included 30 ITP patients and 10 controls. Identification and enumeration of Plasmablast were done by multicolor flow cytometry using specific antibody panels (CD19, CD27 & CD38) and sequential gating using FACSCanto flow cytometer and FlowJo software. We found that lymphocytes subpopulation in ITP patients and controls revealed increase in frequency of CD19 (B lymphocytes) in acute, persistent, and chronic ITP patients in comparison with controls (p < 0.001, 0.023, 0.001) respectively. Plasmablast cells could play a role in the pathogenesis of ITP and might guide therapy in ITP patients in the future.

Safety and Efficacy of Thrombopoietin Analogs in the Treatment of Chronic Thrombocytopenic Purpura in Children: A Systematic Review

IntroductionImmune thrombocytopenic purpura (ITP) is an autoimmune disorder consisting of low platelet count, purpura, and hemorrhagic episodes, caused by antiplatelet autoantibodies. Children who develop chronic or refractory ITP are at risk of bleeding after failing first-line therapies. Thrombopoietin analogs -Eltrombopag and romiplostim are safe and effective treatment options. Thrombopoietin receptor agonists (TPO-Ras) improve platelet production by activating the thrombopoietin pathway. They also stimulate megakaryocytes and hematopoietic stem cells. We analyzed the efficacy and toxicity of romiplostim and eltrombopag in chronic immune thrombocytopenic purpura in the pediatric population (1-17 years).Materials/MethodsFollowing the PRISMA guidelines, we performed a comprehensive literature search on Pubmed, Embase, Cochrane Library, Web of Science, and Clinicaltrials.gov. We used the following keywords, “Thrombopoitein analogs”, “TPOs”, “Immune thrombocytopenic purpura”, “Eltrombopag” and “Romiplostim” MeSh terms from the inception of data till 06/17/2021. We screened initial results from the search of 358 articles focusing on the pediatric population and finally included 9 clinical trials and 1 observational study. We excluded all case reports, case series, preclinical trials, review articles, and meta-analyses. We extracted the data for efficacy (platelet response, baseline platelet count, and Platelet count at first response) and safety (Bleeding or Grade ≥ 3 Adverse Events).Results:RomiplostimA total of 185 patients were analyzed in five clinical trials and 1 observational study employing Romiplostim in the treatment group. Platelet response (PR) (platelet count >50 × 109/L) has been reported in all the studies. In 3 randomized double-blinded control trials by Bussel 2011, Elfaly 2011, and Tarantino 2016, Romiplostim achieved a platelet response of 81.69% vs 12.9% in the placebo group.The other three studies reported substantial platelet response as stated in table 1. In all the studies 25 participants had a prior splenectomy. The most common side effects reported in the studies were bleeding (56.75%), headache (58.64%), contusion (50.76%), and epistaxis (49.23%). Clinically significant bleeding (grade 2-4) was reported by 2 studies in Romiplostim vs placebo group (71.08% vs 96%).EltrombopagA total of 246 patients were analyzed in five clinical trials and 1 observational study. In a randomized double-blinded multicenter study by Grainger et al., Eltrombopag achieved a PR of 39.68% vs 3.4% in the placebo group. Other clinical trials reported a PR of 55.85% whereas the observational study by Neuner et al. reported a PR of 72% in the patient population. Clinically significant bleeding was reported by Grainger et al. and was 47 % in the eltrombopag group vs 7% in the placebo group. Fifteen patients in all the studies had a prior splenectomy.Conclusion:Thrombopoietin analogs such as romiplostim and eltrombopag show substantial platelet response and are associated with minimal side effects. However, more randomized clinical trials are needed to compare their head-to-head efficacy and safety in the treatment of chronic immune thrombocytopenic purpura in pediatric patients. [Display omitted] DisclosuresAnwer: Janssen pharmaceutical: Honoraria, Research Funding; GlaxoSmithKline: Research Funding; Allogene Therapeutics: Research Funding; BMS / Celgene: Honoraria, Research Funding.

Association between Vitamin D Receptor Gene Polymorphisms with Immune Thrombocytopenic Purpura in Children

Association between Vitamin D Receptor Gene Polymorphisms with Immune Thrombocytopenic Purpura in Children

Incidence and outcomes of refractory immune thrombocytopenic purpura in children: a retrospective study in a single institution

Treatment of children with refractory immune thrombocytopenic purpura (ITP) is challenging and poorly established. We retrospectively reviewed the clinical data of 87 patients under the age of 16 years who were diagnosed with ITP from April 1998 to March 2017 in our institution. Refractory ITP was defined as a platelet count of < 50 × 109/L at 14 days after receiving intravenous immunoglobulin (IVIG) and prednisolone. We presumed that there was a pathophysiological overlap between refractory ITP and refractory thrombocytopenia (RT): a subtype of refractory cytopenia of childhood (RCC). Immunosuppressive therapies including anti-thymocyte globulin and cyclosporine (CsA) have been adopted for children with RCC in Japan. Thus, from 2009 onwards, we changed the diagnosis from refractory ITP to RT and introduced CsA for refractory ITP/RT. Nine of 42 patients developed refractory ITP in the 1998–2008 group, who received conventional treatments such as IVIG and steroid therapy. Eight of 45 patients developed refractory ITP in the 2009–2017 group, who received CsA with or without IVIG therapy. The response rate at three years after diagnosis was significantly higher in the 2009–2017 group (98%) than in the 1998–2008 group (83%) (p = 0.019). In conclusion, our strategy of introducing CsA for refractory ITP/RT contributed to better outcomes.

Splenectomy

Laparoscopic splenectomy has become an established standard of care in the management of surgical diseases of the spleen, except in the hemodynamically unstable trauma patient requiring splenectomy. Although adoption of minimally invasive splenectomy has led to a gradual decrease in the indications for open splenectomy, both procedures are still essential components of spleen surgery. This review describes the indications and contraindications for procedure, preoperative preparation and consent, operative anatomy and technique, and long-term follow-up. Tables review the clinical indications for splenectomy, classification of splenectomy, a comparison of laparoscopic versus open postsplenectomy outcomes, indications and contraindications for partial splenectomy, and reported incidences of postoperative outcomes and complications after splenectomy. Figures depict splenomegaly, the American Society of Hematology 2011 evidence-based practice guidelines for management of primary idiopathic thrombocytopenic purpura in children and adults, a splenic mass, a splenic cyst, massive splenomegaly, laparoscopic splenectomy, the 2014 Centers for Disease Control and Prevention recommendations for adult and pediatric splenectomy vaccination, splenic artery embolization, various laparoscopic approaches to splenectomy, splenic vascularization, division of splenic artery branches, suspensory ligaments of the spleen, laparoscopic exposure and transection of splenic hilum, retrieval bags and related procedures, open splenectomy, stapling, and laparoscopic partial splenectomy. Videos demonstrate purely laparoscopic splenectomy and hand-assisted laparoscopic splenectomy. This review contains 26 figures, 5 tables, 2 videos, and 111 references.

Immune-mediated thrombotic thrombocytopenic purpura in childhood treated by caplacizumab, about 3 cases.

Immune-mediated thrombotic thrombocytopenic purpura (iTTP) is a rare disease in adults and exceptional in childhood. Caplacizumab has proven its effectiveness in the treatment of iTTP in adulthood in association with standard of care. Unfortunately, this treatment is restricted to adults. We report our experience in three children who were treated successfully with caplacizumab.

Thrombopoietin receptor agonists for pediatric refractory chronic immune thrombocytopenia

Various treatments have been used to treat chronic immune thrombocytopenic purpura in children; however, none of it has been established as the standard of care. The administration of thrombopoietin receptor agonists (TPO-RAs) has been approved as a new treatment option in Japan. In this case series, TPO-RAs were administered to 16 patients (eltrombopag, n=9; romiplostim, n=7). Excluding the data of two patients who underwent splenectomy immediately after starting treatment with these medicines, platelet counts increased to ≥50,000/µl in seven patients. The adverse events recorded were grade 2 liver dysfunction (n=1), according to the common terminology criteria for adverse events version 4, and myelofibrosis (classified as MF1 or mild reticulin fibrosis), as observed on bone marrow biopsy (n=2). We continued the administration of TPO-RAs at the same dose in these patients because the complications they experienced were mild. The risk of adverse events associated with long-term use of TPO-RAs in this pediatric population remains unclear, and a prospective evaluation is needed.

The Role of Helicobacter Pylori Infection in Idiopathic Thrombocytopenic Purpura in Children

Background: Many studies had found obvious relation between helicobacter pylori infection and chronic idiopathic thrombocytopenic purpura; several studies have reported remission of immune thrombocytopenic purpura (ITP) after eradication of a coexistent Helicobacter pylori infection in adults, data in children are limited. Objective: To detect the association of H. pylori infection and idiopathic thrombocytopenic purpura in children and the effect of eradication of the infection on platelet count in these patients. Patients and methods: This study was conducted on 83 chronic idiopathic thrombocytopenic purpura children with age range from 3 to 13 years. They were 46 males 37 females. Also the study included 104 healthy individual with the same range of age. They were 58 males and 46 females as a control group. This was between October 2018 and September 2019 in the Pediatric Hematology and GIT Clinics or inpatients wards of Pediatric Department. Results: Clinical benefit occurred in 31 cases of the 83 chronic ITP (cITP) patients screened; nevertheless, we have a simple, inexpensive, non‐invasive screening method; the adverse events of eradication therapy are negligible, together with an affordable cost, all uncommon attributes among the specific treatments currently available for cITP; therefore it is worthwhile to test for and treat H. pylori infection. Conclusion: Our data showed a prevalence of H. pylori infection in cITP pediatrics that was similar to other studies. We found that successful H. pylori eradication induced platelet response in 37.3% of 83 cases included in our study.

The Role of Helicobacter Pylori Infection in Idiopathic Thrombocytopenic Purpura in Children

Background: Many studies had found obvious relation between helicobacter pylori infection and chronic idiopathic thrombocytopenic purpura; several studies have reported remission of immune thrombocytopenic purpura (ITP) after eradication of a coexistent Helicobacter pylori infection in adults, data in children are limited. Objective: To detect the association of H. pylori infection and idiopathic thrombocytopenic purpura in children and the effect of eradication of the infection on platelet count in these patients. Patients and methods: This study was conducted on 83 chronic idiopathic thrombocytopenic purpura children with age range from 3 to 13 years. They were 46 males 37 females. Also the study included 104 healthy individual with the same range of age. They were 58 males and 46 females as a control group. This was between October 2018 and September 2019 in the Pediatric Hematology and GIT Clinics or inpatients wards of Pediatric Department. Results: Clinical benefit occurred in 31 cases of the 83 chronic ITP (cITP) patients screened; nevertheless, we have a simple, inexpensive, non‐invasive screening method; the adverse events of eradication therapy are negligible, together with an affordable cost, all uncommon attributes among the specific treatments currently available for cITP; therefore it is worthwhile to test for and treat H. pylori infection. Conclusion: Our data showed a prevalence of H. pylori infection in cITP pediatrics that was similar to other studies. We found that successful H. pylori eradication induced platelet response in 37.3% of 83 cases included in our study.

Induction of the remission of immune thrombocytopenic purpura

Abstract. A review of the literature on remission of immune thrombocytopenic purpura in children and a retrospective analysis of its course in a young patient who was successively applied, first to no avail, standard drug therapy, and then, due to the lack of effect, a physiotherapy technique based on the principles of activation therapy. It is known that immune thrombocytopenic purpura is a rare acquired autoimmune disease characterized by isolated thrombocytopenia with the occurrence of hemorrhagic syndrome of varying severity, which can lead to fatal bleeding. At the same time, antiplatelet antibodies are detected only in half of patients suffering from immune thrombocytopenic purpura, and therefore are not a necessary criterion for diagnosis, which in turn makes it difficult to diagnose the disease and does not allow them to be used as a criterion for the effectiveness of treatment. Despite the fact that in childhood, most cases of immune thrombocytopenic purpura occur in acute form, often with the development of spontaneous remission, but in a significant part of patients, relapses of the disease are accompanied by significant thrombocytopenia, hemorrhagic syndrome, and a decrease in the quality of life, which requires specific therapy up to splenectomy. When using the Reverse wave technique in the treatment of immune thrombocytopenic purpura, a stable, long-term remission was achieved in a young patient. The prospects of studying the application of this physiotherapy technique in clinical practice are discussed.

Результаты лечения высокогорным климатом иммунной тромбоцитопении у детей в Кыргызской Республике (пятилетний анализ)

Введение: Вопрос о дальнейшем совершенствовании базисной терапии иммунной тромбоцитопении (ИТП) по-прежнему широко обсуждается специалистами и является предметом оживленных дискуссий. Цель исследования: оценить эффективность высокогорной климатотерапии при хронической ИТП у детей за 5-летний период наблюдения после ежегодного лечения на высокогорной базе. Материалы и методы: В исследование включено 22 ребенка с хронической ИТП в возрасте от 3 до 14 лет, средний возраст — 6,30 ± 1,02 года, длительность заболевания 2-8 лет. Для лечения детей поднимали на высокогорную базу. Продолжительность лечения в высокогорье составляла 40 дней. Результаты: Из 22 детей, получивших 5 курсов высокогорной климатотерапии, у двоих наблюдали полную ремиссию в виде увеличения тромбоцитов более 100×109/л без кровоточивости. Объективный ответ в виде двукратного увеличения числа тромбоцитов, но менее 100×109/л без кровоточивости установлен у 18 детей, отсутствие эффекта было зарегистрировано у 2 детей. Заключение: Повторные курсы высокогорной климатотерапии способствуют улучшению клинической картины, существенному повышению числа тромбоцитов в периферической крови и достижению ремиссии при ИТП у детей. Background: Further development of basic treatment of immune thrombocytopenia (ITP) is still widely discussed by specialists and is the subject of lively discussions. Objectives: to assess the effi ciency of high-altitude climatotherapy in children with chronic ITP for a 5-year follow-up period after annual treatment at high-altitude base. Patients/Methods: The study included 22 children with chronic ITP from 3 to 14 years, the average age was 6.30 ± 1.02 years, and disease duration was 3-8 years. Children were raised to high-altitude base. Treatment duration was 40 days. Results: 22 children received 5 courses of high-altitude climatotherapy. Complete remission was observed in 2 patients with increasing of platelets more than 100×109/L without bleeding. In 18 children an objective response was found in the form of twofold increasing of platelets number, but less than 100×109/L without bleeding; no effect was recorded in 2 children. Conclusions: Repeated courses of high-altitude climatotherapy improve clinical characteristics, significantly increase the number of platelets in the peripheral blood and contribute to remission in children with ITP.

Efficacy and Safety of Anti-D for Acute Immune Thrombocytopenic Purpura in Children in El-Nasr Hospital - Case Report

Efficacy and Safety of Anti-D for Acute Immune Thrombocytopenic Purpura in Children in El-Nasr Hospital - Case Report

Immune Thrombocytopenic Purpura in Children - A Review

Immune Thrombocytopenic Purpura in Children - A Review

Predictors of In-Hospital Mortality in Thrombotic Thrombocytopenic Purpura in Children in the United States: A Population Analysis.

Despite proven efficacy and increased availability of therapeutic plasma exchange, thrombotic thrombocytopenic purpura (TTP) is associated with significant morbidity and mortality. This study utilized the Kids' Inpatient Database and National Inpatient Sample (2003 to 2016) to study predictors of in-hospital mortality in hospitalized TTP patients. Adjusted odds ratios of death with various putative risk factors were calculated using multiple regression analysis. Among 1568 hospitalizations with TTP as primary admission diagnosis who underwent therapeutic plasma exchange, 69 deaths were identified (all-cause mortality, 0.04%; median time-to-death, 6 wk). Overall, hospitalizations rates were fairly similar across the study period. The overall incidence of TTP related hospitalizations is 1.51 per 100,000 hospitalizations. A total of 69 deaths were reported with an all-cause in-hospital mortality rate of 0.04% (69/1568). The median time-to-death was 6 weeks. The majority of deaths occurred in age 16 to 20 years (58%), females (56.5%), and African American (42.9%) as shown in Table 2. Mean age for nonsurvivors was 14 years and the mean age of 15 years for survivors (P=0.01). Younger age, male sex, African-American ethnicity, malignancy, sepsis, acute kidney injury, platelet transfusion was significantly associated with mortality in patients with TTP. Early and targeted therapy for high risk individuals should be used to guide management of TTP patients for improved survival outcomes.

Efficacy and Safety of Eltrombopag for the Treatment of Chronic Idiopathic Thrombocytopenic Purpura in Children and Adolescents

Background: Chronic ITP is a very common disease in children. Most treatment options have focused on slowing platelet destruction like corticosteroids and IVIG. These treatments are not always effective, or have only a transient effect, and treatment related adverse events often restrict further use. Impaired platelet production has been evolved as a potential disease mechanism for ITP. As a result, growth factor and growth factor analogue stimulation of megakaryopoiesis has also been investigated. Objective: is to evaluate the efficacy and safety of eltrombopag for the treatment of children and adolescents with chronic ITP. Subjects and methods: It was a prospective cohort study which was conducted on forty patients (22 males and 18 females) with chronic ITP. They were treated with eltrombopag for a period ranged from 6 months to 2 years after failure of first line of treatment (steroids, IVIG or both). Patients started eltrombopag with mean initial platelet count 14.4 X 103 / uL and were evaluated after at least 6 months of therapy. The study was approved by the academic and medical ethics committee of Zagazig University and a written informed consent was obtained from all patients. Results: Thirty patients (75%) responded to eltrombopag with a mean platelet count of 100.9 X103/ uL while 10 patients (25%) did not respond to the drug. Mean platelet count was significantly higher after eltrombopag therapy (100.9 ± 65.97 versus 14.4 ± 8.87, P < 0.001). The longer the duration of treatment, the higher the mean platelet count after treatment (r = 0.4, P < 0.001). Only 43.3% of responders received combined treatment with IVIG and steroids versus 20% of non-responders (p = 0.006). Conclusion: Eltrombopag is an effective, well tolerated and safe drug to restore platelet counts at levels high enough to prevent bleeding events in children with chronic ITP.