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Childhood idiopathic thrombocytopenic purpura in the Nordic countries: Epidemiology and predictors of chronic disease
Abstract
Aim: To describe the epidemiology of idiopathic thrombocytopenic purpura (ITP) in the Nordic countries, to define clinical subgroups and to investigate factors predicting chronic disease. Methods: A prospective registration was done from 1998 to 2000, including all children with newly diagnosed ITP aged 0–14 y and at least one platelet count <30×109/l. Results: 506 children were registered and 423 followed for 6 mo. The incidence was 4.8/105 per year. Most children were aged 0–7 y (78%), with a predominance of boys, while patients aged 8–14 y had equal representation of the two sexes. There were seasonal variations determined by variations in postinfectious cases with sudden onset. The platelet count was <10×109/l in 58%, but bleeding manifestations were mild or moderate in 97%. The insidious form (symptoms for more than 2 wk) was more frequent in older children and girls, showed little seasonal variation, had milder manifestations and ran a chronic course in more than half the cases. Intracranial haemorrhages did not occur in the first 6 mo after diagnosis. Chronic ITP developed in 25%. The strongest predictor of chronic disease was insidious onset of symptoms (OR 5.97).Conclusion: In the Nordic countries, ITP mainly affects children aged 0–7 y, with a winter bulk of postinfectious cases superimposed on a steady occurrence of non-infectious cases. Clinically, it may be useful to distinguish between children with sudden versus insidious onset of symptoms rather than between different age groups.
... However, 3-5% of children with ITP face a greater risk of bleeding, resulting in significant morbidity and mortality [7], and children with severe thrombocytopenia (platelet counts below the threshold of approximately 30 × 10 9 /L) require investigation and treatment. Importantly, about 20% of children with newly diagnosed ITP may develop chronic thrombocytopenia status (e.g., platelet counts < 100 × 10 9 /L persisting after 12 months) [3,[8][9][10][11]. ...
... Several studies have attempted to identify clinical and laboratory features to predict disease resolution in pediatric ITP [3,[9][10][11][14][15][16][17][18][19][20][21][22][23]. A study conducted in Nordic countries found six parameters associated with remission at 3 and 6 months, including age, sex, onset type, preceding infection, bleeding severity, and platelet count at diagnosis [19,24]. ...
... Using history and clinical features at diagnosis and platelet counts at 1 month post diagnosis, we found that the remission of ITP at 12 months was associated with an abrupt onset of symptoms (<15 days), younger age (<10 years), and positivity for viral serological tests and a vaccination history. These findings are compatible with most of the literature [10,11,14,15,18,19,21]. Our study also showed that patients with positive viral serology tests or vaccination had trends of achieving disease remission between 7 and 12 months post diagnosis. ...
Childhood immune thrombocytopenia (ITP; platelet count < 100 × 109/L) is the most common bleeding disorder in children. A total of 3–5% of children with ITP face a greater risk of bleeding, resulting in significant morbidity and mortality. Childhood ITP is often benign and self-limited; however, children with severe ITP (platelet count < 30 × 109/L) require investigation and monitoring. In addition, 20% of ITP patients may not go into remission (platelet counts < 100 × 109/L by 12 months after diagnosis) and may develop chronic ITP. The early identifying predictors associated with the resolution of severe ITP at the time of diagnosis may be helpful for family guidance. However, there is still controversy about the associations between the clinical factors at the time of initial diagnosis and the definitions of disease remission assessed at different timepoints after diagnosis. This retrospective study aimed to analyze the shared clinical factors among the disease remission definitions at three arbitrarily set timepoints—3, 6, and 12 months after diagnosis. This study retrieved records for hospitalized children aged under 18 years and diagnosed with ITP from the hospital registry in a tertiary university hospital. Clinical variables were recorded by reviewing the medical records with structured data entry for ITP admission. The serial follow-up platelet counts within 12 months after diagnosis were recorded. The times of ITP remission were identified by experienced pediatric hematologists. Patients with mild-form ITP (platelet counts ≥ 30 × 109/L) at diagnosis or who were lost to follow-up within 3 months were excluded. From 1988 to 2019, 546 children were enrolled, and a total of 497 children with severe ITP were included in the further analysis. In total, one (0.2%) died of an intracranial hemorrhage, 363 (73.2%) children went into remission at 3 months, 40 (8.1%) went into remission between 6 and 12 months, and 104 (20.9%) developed chronic ITP. The shared significant predictors for remission by the third, sixth, and twelfth months included pre-adolescent age (<10 years) at diagnosis, abrupt onset (duration of symptoms prior to admission ≤ 2 weeks), and speedy recovery (platelet count > 100 × 109/L at 1 month post diagnosis). ITP patients with positive viral serology tests or vaccination within 4 weeks had trends of delayed remission. In conclusion, diagnosis before preadolescent age, abrupt onset, and speedy recovery may share favorable factors for the remission of childhood ITP assessed at different timepoints.
... Male paediatric patients appear to be more frequently affected by ITP in the range of 0 to 7 years, whereas in older children the sexes show an equal representation. In the same study a rise of the incidence was reported in the winter months for children (Zeller et al., 2005). ...
... For other vaccinations there seems to be an increased risk of ITP, but the possible association requires further research (O'Leary et al., 2012). Around 60% of paediatric patients with newly diagnosed ITP present themselves with a preceding viral infection within the last month in their history (Kühne et al., 2003;Zeller et al., 2005). ...
... Factors for self-limiting disease: Younger age, low platelet count, and short duration of bleeding symptoms before diagnosis have been associated with a higher possibility for a selflimiting disease (Ahmed et al., 2004;Bennett et al., 2018;Glanz et al., 2008;Revel-Vilk et al., 2013;Zeller et al., 2005). A study with almost 500 children developed the following risk classification to predict recovery from ITP at different moments from point of diagnosis. ...
Objectives: Childhood ITP remains not as well understood as ITP in adults. In consequence, there is no complete reliable statement on the course of childhood ITP patients and no proper German guideline which supports clear statements on therapy. Under these circumstances the aim of this work is to support factors about the course of patients at initial diagnosis and to show the adherence of the current guideline for childhood ITP in past therapies. In this way we try to identify problems in the clinical practice, which should be more in focus to enhance the present guideline. In this manner, we hope to support starting points to improve therapy and education on childhood ITP and in consequence to improve the quality of life in children with ITP. Design & Methods: In this retrospective study 89 childhood patients from the age of 0 to 17 years of the University Paediatric Hospital Erlangen, who had their initial diagnosis ITP between 01.01.2000 and 30.06.2016, were analysed. Parameters chosen for analysis with prognostic factors were their age, sex, prior infection status, bleeding severity, therapy, and thrombocyte count at initial diagnosis. In comparison to the German guideline of childhood ITP 65 patients were evaluated with their length of initial hospital stay, therapy, and amount of blood samples. Observations & Results: We could not significantly support any prognostic factor for a chronic disease. Only tendencies toward a more frequent development of a chronic disease for female sex, older age, and absent prior infection supported the cited literature. On the other hand, a treatment with IVIg alone or in combination with steroids as well as a higher thrombocyte count shows the opposite tendency of more patients with these prognostic factors developing a limited disease course. Regarding the German guideline of childhood ITP, a higher amount of hospitalisation and medical therapy of patients which do not certainly qualify for medical treatment (38 of 55 patients with received medical therapy) was seen. Also, patients in need of medical intervention according to the guideline did not always receive medication (3 of 10 patients without medical therapy). In addition, at least 1.35 blood samples per day of inpatients at their initial therapy was documented. Conclusions: This study adds patients to the pool of patients analysed towards their prognostic factors. Related to the current German guideline of childhood ITP, we established focuses which need to be addressed more in order to provide an improved therapy of ITP and in consequence will give the affected children a better quality of life.
... In our study, we examined the risk factors developed by the Nordic Department of Pediatric Hematology and Oncology (NOPHO) [7] and by the meta-analysis published by Heitink Polle et al. [5]. We have found that there is no statistically significant difference between genders in terms of chronicity. ...
... We have found that there is no statistically significant difference between genders in terms of chronicity. However, according to the results published by NOPHO, female gender in all age groups is at risk about chronicity [7]. ...
... [18]. Three studies in this subject recently revealed that the lack of infection and vaccination history of the patient correlates with the progress of chronic disease development [7,9,11]. However, in this study, there was no history of vaccine or infection of the patients in the last 4 months. ...
... In the present study patients with ITP were 25 males and equal number of females with ages ranging from 1 to 17 years old. Although some reports showed that boys and girls are equally affected by childhood ITP (16,17) ; other authors found a slight female predominance in ITP patients with a female: male ratio was 1.2/1 in a populationbased registration of children with ITP that was performed in Norway (18) . On the other hand, Kuhne et al. found that the male: female ratio was in favor of males (54%) in children aged 2-5 years with female patients being older (19) . ...
... While 56% were newly diagnosed. Other reports estimated that the incidence of chronic ITP in childhood was 0.46 per 100,000 children per year with a prevalence of 4.6 per 100,000 children (18) . Edslev et al. found that the platelet count is significantly decreased in both acute and chronic ITP, but it was maximally reduced in patients with acute ITP (20) . ...
... It is an exclusionary diagnosis. [1][2][3] In most cases, the origin of ITP is unknown, but it might be induced by a viral infection or other immunologic or environmental factors. Immune thrombocytopenia in tuberculosis is uncommon, with only a few cases reported to date. ...
... Immune thrombocytopenia in tuberculosis is uncommon, with only a few cases reported to date. 2,4,5 In ITP, thrombocytopenia is defined as a platelet count of 100,000/microL or below. 4,6,7 However, in most case studies, the presenting platelet count is less than 30,000/microL, which is likely due to the fact that patients with mild illnesses are less likely to experience bleeding and may never seek medical help. ...
Background:
Isolated thrombocytopenia with normal levels of other cell lines in the absence of other reasons is referred to as "immune thrombocytopenic purpura" (ITP). Tuberculosis has been associated with a variety of hematologic abnormalities, although severe thrombocytopenia and tuberculosis presenting as immune thrombocytopenic purpura are extremely uncommon.
Case presentation:
We discuss a case of an 11-year-old male adolescent who came with epistaxis and petechial rash lasting one day, as well as severe thrombocytopenia. Following the clinical diagnosis of ITP, the patient was started on prednisone, transfused with platelets, and later started on antituberculosis (ATT) after confirmation of tuberculosis. The patient had a satisfactory response during the course of treatment, and the platelet level was fully recovered after 6 months.
Conclusion:
Tuberculosis (TB) should be recognized as a cause of immunological thrombocytopenia in tuberculosis-endemic areas. Our patient's platelet count improved after 1 week of ATT and 2 weeks of prednisolone, and it was entirely restored after 6 months of ATT treatment. Unfortunately, there are no clear guidelines for treating TB-related immune thrombocytopenia or determining the cause of TB-related immune thrombocytopenia. Tuberculosis-induced ITP resolves with the ATT, even though more investigation is warranted.
... Noteworthy, it has been shown that the risk of severe bleeding is not necessarily correlated with platelet counts unless the absolute platelet count is lower than 20×10 9 /L, as other factors such as age, lifestyle and other clinical condition of the patient may play a role (12)(13)(14)(15)(16)(17). Noteworthy, while there are similarities between children and adults with ITP, there is increased evidence that highlight several distinctive characteristic of adult ITP, such as higher rates of comorbidities and chronicity compared to children with ITP (18)(19)(20), and which can be valuable characteristics to further improve and personalize the diagnosis and treatment of this disease. ...
... One of the most well-documented distinctions between adult and children is that ITP in most pediatric patients tends to be acute/transient and more likely resolved eventually without any treatment. Most children undergo spontaneous remission and rarely experience active bleeding, although most of these patients still experience skin bruising and bleeding (5,6,18,19). Chronic ITP, however, is more prevalent in adult patients (~ 70-80%) and difficult to treat, as adults with ITP tend to have a higher risk of bleeding and a lower spontaneous remission rate (4,23,118). ...
Intravenous immunoglobulin (IVIg) has been used for almost 40 years as a biologic therapeutic for the treatment of immune thrombocytopenia (ITP). Originally found to ameliorate ITP in pediatric patients, IVIg is now used to treat adult patients with acute and chronic ITP and has become a first-line therapy for this autoimmune disease. Treatment in adult ITP usually consists of high-doses of IVIg, usually 1-2 g/kg given as one bolus dose or over 4 to 5 days. Success rates vary but in adults with acute ITP, response rates are around 60% but often the response is transient. In chronic ITP, IVIg is not as efficacious and is often used in combination with other therapeutics, such as glucocorticoids or rituximab or, rarely, these patients will undergo splenectomy. Despite its many years of use, the mechanism of action of IVIg in ITP remains controversial. Although IVIg has a good record of low toxicity in adult patients, most products contain anti-A and anti-B iso-agglutinins, which can cause hemolysis in non-blood group O patients, sometimes life-threatening, with blood group AB patients being at highest risk for a severe hemolytic episode. In addition, IVIg is expensive and is susceptible to world-wide shortages due to its human source material and expanding use to treat various autoimmune/inflammatory diseases. Despite these caveats, IVIg will likely continue to be a first-line therapy for adult ITP, particularly if bleeding.
... ITP, also known as idiopathic thrombocytopenic purpura or immune thrombocytopenic purpura, is a condition characterized by a low platelet count caused by autoantibodies targeting platelet antigens [3]. ITP is a hematologic disorder that is relatively common, with the highest incidence observed in the pediatric population [4]. Approximately 40% of cases occur in children under 10 years of age [5]. ...
Gut microbiota have been linked to immune thrombocytopenia (ITP) and Henoch–Schönlein purpura (HSP) in recent studies, but a cause-and-effect relationship is unclear. We used Mendelian randomization (MR) to assess causal relationships between gut microbiota and HSP/ITP using summary statistics from the GWAS dataset of the international MiBioGen and FinnGen consortium. The IVW method was used as the main evaluation indicator. MR analysis of 196 intestinal flora and HSP/ITP/sTP phenotypes showed that 12 flora were potentially causally associated with ITP, 6 with HSP, and 9 with sTP. The genes predicted that genus Coprococcus3 ( p = 0.0264, OR = 2.05, 95% CI 1.09–3.88)and genus Gordonibacter ( p = 0.0073, OR = 1.38; 95% CI 1.09–1.75) were linked to a higher likelihood of developing ITP. Additionally, family Actinomycetaceae ( p = 0.02, OR = 0.51, 95% CI 0.28–0.90) and order Actinomycetales ( p = 0.0199, OR = 0.50, 95% CI 0.28–0.90) linked to reduced HSP risk. Genus Ruminococcaceae UCG013 ( p = 0.0426, OR = 0.44, 95% CI 0.20–0.97) negatively correlated with sTP risk. Our MR analyses offer evidence of a possible cause-and-effect connection between certain gut microbiota species and the likelihood of HSP/ITP.
... ITP can present either as a primary disorder or secondary to other diseases, such as infections or altered immune conditions [1,2]. The incidence of ITP varied from two to five per 100 000 children younger than 15 years [3]. ...
... Trong một nghiên cứu năm quốc gia Bắc Âu (1998)(1999)(2000), tỷ lệ mắc hàng năm là 4,8/100.000 trẻ dưới 15 tuổi [1]. Theo James B Bussel (2019) cho thấy tỷ lệ mắc là từ 1-6,4/100.000 ...
Nghiên cứu nhằm mô tả đặc điểm và một số yếu tố liên quan đến mức độ xuất huyết ở trẻ từ 2 tháng đến 15 tuổi mắc bệnh xuất huyết giảm tiểu cầu miễn dịch tại Bệnh viện Trung ương Thái Nguyên. Đối tượng được đưa vào nghiên cứu gồm 42 trẻ từ 2 tháng đến 15 tuổi được chẩn đoán là xuất huyết giảm tiểu cầu miễn dịch tại Bệnh viện Trung ương Thái Nguyên từ tháng 6/2021 đến hết tháng 5/2023. Phương pháp nghiên cứu được sử dụng là nghiên cứu mô tả cắt ngang. Kết quả nghiên cứu cho thấy bệnh xảy ra quanh năm, gặp nhiều nhất ở lứa tuổi từ 2 tháng đến 5 tuổi, tỷ lệ nam nhiều hơn nữ. Biểu hiện xuất huyết dưới da chiếm 100%, trong đó xuất huyết dưới da và niêm mạc chiếm tỷ lệ cao nhất 69%, xuất huyết nội tạng ít gặp. Số lượng tiểu cầu lúc vào viện thấp, 78,6% trẻ có số lượng tiểu cầu < 20000/mm3. Mức độ xuất huyết của bệnh liên quan đến số lượng tiểu cầu. Không thấy mối liên quan giữa độ tuổi, thiếu máu và mức độ xuất huyết.
... 11 At diagnosis, non-severe thrombocytopenia (>20 × 10 9 /L) is also associated with a risk of chronic ITP, 11 whereas severe thrombocytopenia (<5 × 10 9 /L) is associated with a low risk of chronicity. 12 Further, Schmidt et al developed a score that gathered these factors into a recovery score displaying good performance to predict a prolonged disease for a given patient. 13 However, their model does not account for platelet duration over time. ...
Childhood immune thrombocytopenia (ITP) is a rare autoimmune disorder characterized by isolated thrombocytopenia. Prolonged ITP (persistent and chronic) leads to a reduced quality of life for children in many domains. To provide optimal support for children, with ITP, it is important to be able to predict those who will develop prolonged ITP. This study aimed to develop a mathematical model based on platelet recovery that allows the early prediction of prolonged ITP. In this retrospective study, we used platelet counts from the 6 months following the diagnosis of ITP to model the kinetics of change in platelet count using a pharmacokinetic–pharmacodynamic model. In a learning set (n = 103), platelet counts were satisfactorily described by our kinetic model. The K heal parameter, which describes spontaneous platelet recovery, allowed a distinction between acute and prolonged ITP with an area under the curve (AUC) of 0.74. In a validation set (n = 58), spontaneous platelet recovery was robustly predicted using platelet counts from 15 (AUC = 0.76) or 30 (AUC = 0.82) days after ITP diagnosis. In our model, platelet recovery quantified using the k heal parameter allowed prediction of the clinical course of ITP. Future prospective studies are needed to improve the predictivity of this model, in particular, by combining it with the predictive scores previously reported in the literature.
... Several studies have estimated the annual incidence to be between 1 and 6.4 cases per 100,000 children (2,5,6) .ITP can affect any age, but there is a peak incidence between two and five years, . Children younger than 10 years of age are more likely to remit than older (7,8 ) .ITP is characterized by a variety of skin and mucous membrane bleeding manifestations such as petechiae, purpura, bruising, epistaxis, gingival bleeding, and menorrhagia.Severe intracranial bleeding is extremely rare, occurring in 0.5-15 when the platelet count drops below 10×10 9 / L (9). ...
... The annual prevalence of ITP in adults was 22 per million people. 5 There is no marked difference in the clinical signs of ITP among patients, although ITP may start acutely and suddenly, but in most cases, it has an insidious onset. Bleeding in symptomatic patients can range from mild petechiae and bruising to severe hemorrhage, and symptoms of bleeding from thrombocytopenia often occur as mucocutaneous bleeding. ...
... Among the biological factors tested, only the presence of antinuclear antibodies and the platelet count at diagnosis have been shown to be associated with the clinical course of ITP (11). At diagnosis, low thrombocytopenia (> 20x10 9 /L) is also associated with a risk of chronic ITP (11), whereas stronger thrombocytopenia (< 5x10 9 /L) is associated with a low risk of chronicity (12). Further, Schmidt et al. developed a score which gathered these factors into a recovery score displaying good performance to predict a prolonged disease for a given patient (13). ...
Introduction : Childhood immune thrombocytopenia (ITP) is a rare autoimmune disorder characterized by isolated thrombocytopenia. Prolonged ITP (persistent and chronic) leads to a reduced quality of life for children in many domains. To provide optimal support for children, with ITP, it is important to be able to predict those who will develop prolonged ITP. This study aimed to develop a mathematical model based on platelet recovery that allows the early prediction of prolonged ITP. Methods : In this retrospective study, we used platelet counts from the six months following the diagnosis of ITP to model the kinetics of platelet evolution using a pharmacokinetic-pharmacodynamic model. Results : In a learning set (n=103), platelet counts were satisfactorily described by our kinetic model. The K parameter, which describes spontaneous platelet recovery, allowed a distinction between acute and prolonged ITP with an AUC of 0.74. In a validation set (n=58), spontaneous platelet recovery was robustly predicted using platelet counts from 15 (AUC=0.76) or 30 (AUC=0.82) days after ITP diagnosis. Discussion : In our model, platelet recovery quantified using the k parameter allowed prediction of the clinical course of ITP. Future prospective studies are needed to improve the predictivity of this model, in particular, by combining it with the predictive scores previously reported in the literature.
... ITP frequently exists with the rapid manifestation of a petechial rash, bruising, and/or bleeding in a healthy individual. Approximately 60 percent of children with newly diagnosed ITP have a background of a preceding viral illness within the past month [6]. Numerous viruses have been identified as triggers of ITP, including influenza, Epstein-Barr virus, hepatitis B, hepatitis C, varicella zoster virus, and HIV [7]. ...
Immune Thrombocytopenic Purpura (ITP) of childhood is identified as isolated thrombocytopenia. While it can be triggered by a viral infection such as hepatitis B, hepatitis C, cytomegalovirus, Epstein-Barr, influenza, herpes, varicella-zoster, and HIV or other immune causes, the reason for ITP remains unknown in most patients. We reported a pediatric case with ITP whose COVID-19 total antibody test was positive. Despite the poor response of high dose intravenous immunoglobulin (IVIG), steroid treatment generated a good result. Our patient had an asymptomatic Severe Acute Respiratory Syndrome Coronavirus 2, SARS-CoV-2 infection (COVID-19 infection) and COVID-19 PCR was negative. Since we are in the period of the COVID-19-related pandemic, SARS-CoV-2 should be kept in mind in the etiology of ITP. This case raises awareness of both PCR and antibody screening for COVID-19 in patients with ITP, especially in the pandemic season.
... The annual prevalence of ITP in adults was 22 per million people. 5 There is no marked difference in the clinical signs of ITP among patients, although ITP may start acutely and suddenly, but in most cases, it has an insidious onset. Bleeding in symptomatic patients can range from mild petechiae and bruising to severe hemorrhage, and symptoms of bleeding from thrombocytopenia often occur as mucocutaneous bleeding. ...
Millions of people around the world were, or are still involved with COVID-19 due to infection with SARS-CoV-2. In addition to hallmark symptoms, thrombotic problems, lymphopenia, and thrombocytopenia have also been reported in COVID-19 patients, of which ITP is the most common and occurs in more than one-third of COVID-19 patients. Hyperinflammation, cytokine storms, and generally immune dysregulation in a percentage of patients develop the main consequences of diseases such as ALI, ARDS and multiple organ failure. Some of the important events in the immunopathogenesis of this disease are disruption of T-cell effector differentiation and the destructive role of Th17 lymphocytes, neutrophil function and inflammatory macrophages. NLRP3-inflammasome hyperactivity causes serious dysfunction of innate immune cells and, consequently, T lymphocytes in many inflammatory disorders, most notably in the COVID-19. A closer look at the immunopathogenesis of ITP and COVID-19 brings us to common ground. The purpose of this study was to review and summarize the findings of various studies on the immunopathogenesis of ITP and its possible causes in COVID-19. Finally, enhanced differentiation of Th17 and Th1, the cell death called as pyroptosis, hyperinflammation and dysfunction of inflammatory neutrophils and macrophages, and NLRP3- inflammasome hyperactivity are important factors in the development of thrombocytopenia in patients with COVID-19. Further studies are needed to better understand immunopathogenesis and effective treatments for ITP, especially in inflammatory disorders
... ITP has been identified after various viral infections including hepatitis B/C viruses (HBV/HCV), cytomegalovirus (CMV), varicella zoster virus (VZV), human immunodeficiency virus (HIV) (2). A new one has been added to these viral infection agents with the start of reporting of COVID-19 related immune thrombocytopenic purpura cases (3)(4)(5). ...
İmmün trombositopenik purpura (İTP), izole trombositopeni ile kendini gösteren hematolojik bir hastalıktır. Etiyolojisinde son bir aydaki viral enfeksiyonlar sıklıkla bulunur. COVİD-19 enfeksiyonu sonrası çeşitli hematolojik komplikasyonların yanı sıra ITP gelişimi de görülebilmektedir. Bu yazıda COVİD-19 enfeksiyonu sırasında teşhis edilen ve kanama bulgusu olmayan bir çocuk akut ITP olgusu sunulmaktadır.
... ITP has a higher prevalence among children than adults. The annual prevalence of ITP in adults is 22 per million people [7][8][9]. The exact etiology of ITP is still unknown but genetic and other triggering factors appear to be involved [10,11]. ...
SUMMARY
Following the outbreak of the COVID-19 pandemic, millions of people around the world have been affected with SARS-CoV-2 infection. In addition to the typical symptoms, thrombotic events, lymphopenia, and thrombocytopenia have been reported in COVID-19 patients. Immune thrombocytopenic purpura (ITP) is one of the thrombotic events that occur in some COVID-19 patients. Hyperinflammation, cytokine storms, and immune dysregulation in some patients are the cause to the main COVID-19 complications such as ALI (acute lung injury), acute respiratory distress syndrome (ARDS), and multiple organ failure. Disruption in the differentiation of T-cells, enhanced differentiation of Th17 and Th1, cell death (pyroptosis), hyper-inflammation and dysfunction of inflammatory neutrophils and macrophages, and hyperactivity of NLRP3-inflammasome are among the important factors that may be the cause to COVID-19-induced ITP. This study aimed to give an overview of the findings on the immunopathogenesis of ITP and COVID- 19-induced ITP. Further studies are required to better understand the exact immunopathogenesis and effective treatments for ITP, especially in inflammatory disorders.
Keywords: COVID-19, SARS-CoV-2, inflammasome, immune thrombocytopenic purpura, platelets, immune dysregulation.
... 21 This is contrary to childhood ITP, where a significant seasonal trend has been identified. 20,[22][23][24] Seasonality among children diagnosed as ITP might be due to the seasonality of certain viral infections such as influenza, which is responsible for most of the childhood ITP cases. 24 ITP in adults on the other hand has a chronic course and insidious onset with no associated viral and other infections. ...
Context
Author observed certain hematological disorders clustering in certain part of the year, however no authentic data or local study was found which covered these disorders in the context of seasonal variations.
Objectives
To assess the seasonal variations in hematological disorders among patients diagnosed based on bone marrow biopsy.
Design
We retrospectively reviewed the 10-year records of hematological disorders among patients from year 2006 to 2015.
Setting
The study was conducted at National Institute of Blood Disease and included patients who visited their clinics.
Patients and Other Participants
All cases of aplastic anemia (AA), acute lymphoblastic leukemia (ALL), acute myeloid leukemia (AML), immune thrombocytopenic purpura (ITP), and acute promyelocytic leukemia (APML) were categorized based on the seasons in which they were diagnosed such as winter (December-February), spring (March-May), southwest monsoon periods (June-September), and retreating monsoon period (October and November). SPSS and STATA were used for statistics. Inferential statistics were explored using the chi-square test for heterogeneity to evaluate seasonal variations. P-value <0.05 was taken as significant.
Study Outcome Measures
To assess the seasonal variations in hematological disorders among patients diagnosed based on bone marrow biopsy, who attended National Institute of Blood Diseases (NIBD) clinics during 2006 to 2015. Significant seasonal and yearly variations were detected in all diagnosis except the APML.
Results
A total of 1982 cases were reviewed. Men were predominantly higher (n = 1190, 60%) as compared to women (n = 792, 40%). Frequency of ALL was found to be higher (513, 25.9%), followed by ITP (504, 25.4%), AML (490, 24.7%), AA (396, 20%), while APML was observed in only 79 (4%) patients. Seasonal variations in the diagnosis of hematological disorders were observed (P-value < .001), except in APML diagnosis (P-value = .445). Significant seasonal variations were also detected in both genders.
Conclusion
The finding of this study has reported an increase in hematological disorders during 2006 to 2015. Particularly, most of the cases were reported in southwest monsoon period, whereas the least number of cases were reported in retreating period. Significant seasonal and yearly variations were detected in all diagnosis except the APML.
... Immune thrombocytopenic purpura (ITP) is a disorder in which the primary hemostasis process is impaired due to low platelet numbers. The incidence rate of ITP in children is known to be 1.6-5.3 per 100,000 person-years [1][2][3][4][5][6][7][8]. In a recent Korean study, the ITP incidence rate for all ages was 5.3 per 100,000 person-years, while it was 14.3 per 100,000 person-years for children aged < 15 years. ...
Immune thrombocytopenic purpura (ITP) is prevalent in children aged 2–5 years but may occur in all pediatric age groups. In 50–60% of pediatric patients, ITP is preceded by an upper respiratory tract infection 1–4 weeks before its onset. In this study, the relationship between the development of ITP and viral infections in children was assessed. We analyzed data of 6487 patients aged < 18 years with incident ITP from the Health Insurance Review and Assessment Open Access Big Data Platform (2015 to 2018) and the Korea Disease Control and Prevention Agency. The monthly positive detection rate (PDR) of seven respiratory and four acute diarrhea viruses was calculated. The virus PDR seasonal trend data was analyzed through ARIMA modeling. The ITP diagnostic data and prevalence of viral infection 1 and 2 months prior were analyzed using the Granger test. The overall male to female (M/F) ratio was 1.2, whereas it was 1.4 in the youngest age group (< 1 year). The overall ITP incidence rate was 18.1 per 100,000 person-years. Respiratory syncytial virus, rhinovirus, rotavirus, and astrovirus infections influenced ITP occurrence in children. However, rotavirus infection is positively associated with the etiology of ITP after 1–2 months.
... These include sudden appearance of the disease, viral disease preceding the presentation, lower platelet count, age <10 years, male sex, and lack of mucosal bleeding at diagnosis. [6][7][8][9][10][11][12][13][14][15] Interestingly, intravenous immunoglobulin (IVIG) treatment with or without steroids seems to protect against the onset of chronic disease. 7,8 A murine model showed increased platelet apoptosis in response to antibodies against integrin aIIbb3, while this effect was prevented by IVIG treatment. ...
In all, 15–30% of pediatric immune thrombocytopenia (ITP) patients will remain chronically thrombocytopenic at 1 year post diagnosis. All attempts to classify patients at diagnosis have proven unsuccessful. We hypothesized that a different pathophysiology is responsible for non-chronic versus chronic pediatric ITP. We aimed to examine differences in the apoptotic markers’ presentation at diagnosis between non-chronic and chronic patients.
Blood samples were collected from 42 pediatric patients with newly diagnosed ITP prior to initiation of treatment. We incubated patients’ sera with control platelets and compared the results among three research groups: healthy controls, chronic ITP, and non-chronic ITP patients. We measured apoptotic markers phosphatidylserine (PS) exposure and mitochondrial inner membrane potential (ΔΨm) by flow cytometry and the level of human apoptotic proteins by Human Apoptosis Array.
We found increased platelet PS exposure and decreased ΔΨm in response to all ITP patients’ sera compared to control subjects. Human Apoptotic Array revealed an increased expression of five apoptotic proteins: BIM, CD40, IGFBP2, P21, and SMAC, following sera incubation of non-chronic pediatric ITP patients, compared to chronic patients’ sera, at diagnosis.
Our data contribute to knowledge on apoptosis markers that may aid in predicting the prognosis of children with ITP.
The key message of our article is that children with chronic ITP have a different apoptotic profile compared to non-chronic ITP.
Addition to existing literature: This is the first study comparing apoptotic markers between children with chronic ITP to non-chronic ITP.
Impact: Our findings indicate that, in the future, apoptotic markers may help to classify ITP patients into non-chronic versus chronic ones, at diagnosis.
... 21 This is contrary to childhood ITP, where a significant seasonal trend has been identified. 20,[22][23][24] Seasonality among children diagnosed as ITP might be due to the seasonality of certain viral infections such as influenza, which is responsible for most of the childhood ITP cases. 24 ITP in adults on the other hand has a chronic course and insidious onset with no associated viral and other infections. ...
Aims:
To assess the seasonal variations in hematological disorders among patients diagnosed on the basis of bone marrow biopsy, who attended National Institute of Blood Diseases (NIBD) clinics during 2006 to 2015.
Methods:
We retrospectively reviewed the 10-year records of hematological disorders among patients' NIBD clinics from year 2006 to 2015. All cases of aplastic anemia (AA), acute lymphoblastic leukemia (ALL), acute myeloid leukemia (AML), immune thrombocytopenic purpura (ITP), and acute promyelocytic leukemia (APML) were categorized on the basis of the seasons in which they were diagnosed such as winter (December-February), spring (March-May), southwest monsoon periods (June-September), and retreating monsoon period (October and November). Statistical analysis was performed by using SPSS and STATA. Inferential statistics were explored using the chi-square test for heterogeneity to evaluate seasonal variations. P-value <0.05 was taken as significant.
Results:
A total of 1982 cases were reviewed. Men were predominantly higher (n = 1190, 60%) as compared to women (n = 792, 40%). Frequency of ALL was found to be higher (513, 25.9%), followed by ITP (504, 25.4%), AML (490, 24.7%), AA (396, 20%), while APML was observed in only 79 (4%) patients. Seasonal variations in the diagnosis of hematological disorders were observed (P-value < .001), except in APML diagnosis (P-value = .445). Significant seasonal variations were also detected in both genders in stratified analysis.
Conclusion:
The finding of this study has reported an increase in the hematological disorder during 2006 to 2015. Particularly, majority of the cases were reported in southwest monsoon period, whereas least cases were reported in retreating period. Significant seasonal and yearly variations were detected in all diagnosis except the APML.
... Immune Thrombocytopenia (ITP) is usually considered as one of the most common bleeding disorders in children [1]. It generally develops after exposure to common viral infections with peak age of 1-4 year [1,2]. In most of cases, ITP cures spontaneously within 3 months, however, sometimes it becomes chronic and conservative treatments are indicated [3,4]. ...
... This proportion was similar to other studies. In our study the mean age was higher in the chronic group compared to the acute group which was also in agreement with other studies [1][2][3][4][5] . ...
Background: Previous studies about the relationship between bone marrow megakaryocyte count and the chronicity of ITP has yielded paradoxical results. The aim of the present study was to investigate any relationship between the megakaryocyte count in the bone marrow and the chronicity of ITP. Materials and Methods: This study was performed to compare the primary bone marrow aspiration megakaryocyte count, obtained early upon the diagnosis of ITP, between chronic ITP (case) and acute ITP (control) groups among patients aged less than 15 years old, at Mofid Hospital, Tehran and Amir-Kabir Hospital, Arak. Data collected was analyzed using SPSS version 18. The project was approved by local Ethics committee and written informed consent was obtained from all parents. Results: Three hundred and seven patients with ITP including 212 patients with acute ITP (69.1 %) and 95 patients with chronic ITP (30.9 %) participated in the study. The bone marrow megakaryocyte count was increased in 263 patients (85.7 %), decreased in 7 patients (2.3 %), and normal in 37 patients (12.1%). Among 212 patients with acute ITP, the bone marrow megakaryocyte count was increased in 182 patients (85.8 %), decreased in 5 patients (2.4%), and normal in 25 patients (11.8 %). Among 95 patients with chronic ITP, the bone marrow megakaryocyte count was increased in 81 patients (85.3 %), decreased in 2 patients (2.1 %), and normal in 12 patients (12.6%). There was no statistically significant difference between two groups regarding the megakaryocyte count. Conclusion: Based on our findings it seems that the variant of bone marrow megakaryocyte count is not related to the chronicity among patients with ITP.
... This proportion was similar to other studies. In our study the mean age was higher in the chronic group compared to the acute group which was also in agreement with other studies [1][2][3][4][5] . ...
... 2,4,5 The incidence of ITP is the highest among children between 2 and 5 years of age. [6][7][8] ITP is an acute disease in most children, as thrombocytopenia resolves within a few weeks to months in the majority of children. Furthermore, the clinical manifestation of ITP is extremely variable. ...
Oxidative stress may play a role in the pathogenesis of immune thrombocytopenia (ITP), but the role of dynamic thiol/disulfide homeostasis has not been studied. The objective of this study was to assess whether there is a change in thiol/disulfide homeostasis in children with acute ITP. A total of 40 children with acute ITP and 50 healthy age-matched and sex-matched controls were included in this study. Serum total thiol and native thiol levels have been measured with a novel automatic spectrophotometric method. The amount of dynamic disulfide bonds and related ratios were calculated from these values. The average total thiol and native thiol levels of the patient group were found to be significantly lower than those levels of controls (P<0.01). However, intravenous immunoglobulin (IVIG) treatment with 1 g/kg/d prevented these reductions. disulfide level was slightly, but not significantly, depressed in ITP patients, but it recovered following IVIG treatment. We detected no marked changes in disulfide/total thiol, disulfide/native thiol, and native thiol/total thiol ratios between groups. These results are the first to demonstrate that thiol/disulfide homeostasis plays a role in ITP pathogenesis, and IVIG treatment can prevent the reduced thiol levels in children.
Immune thrombocytopenia (ITP) is a reason of thrombocytopenia that is characterized by isolated thrombocytopenia in childhood. Epstein barr virus infection (EBV) is a mildly and uncomplicated ailment that might be a trigger factor for ITP. Here, we discuss two cases with ITP secondary Epstein barr virus infection.
Introduction: Primary immune thrombocytopenia (ITP) is an autoimmune disorder that is distinguished by a low platelet count (
We aimed to investigate the relationship between demographics, clinical features, laboratory findings including monocytosis and clinical course in children with immune thrombocytopenia (ITP). Data of 100 ITP patients were analysed. Complete blood count findings of the patients at certain time points were evaluated to classify the disease as acute, persistent and chronic. An effect of sex on chronicity was not observed (P = 0.166). Of the patients enrolled in the study, 38% (n = 38) had chronic course. The mean age of patients with the chronic course was 7 ± 4.1 years, which was significantly higher than the other groups (P = 0.007). Sixty-five percent (n = 13) of the patients presenting with mucosal bleeding and 27.4% (n = 20) of the patients presenting with skin bleeding became chronic (P = 0.008). MPV was found to be significantly high in chronic ITP patients (P = 0.049). Monocytosis was noted in 80% of the patients at diagnosis. Intravenous immunoglobulin was used in 84% of the patients with acute ITP; 33% of them developed chronic ITP. The age at diagnosis, presence of mucosal bleeding and increased MPV on admission were high-risk factors for the development of the chronic course. Monocytosis was detected in 80% of the patients on admission, and it may play a role in the pathogenesis of ITP.
Primary immune thrombocytopenia is a benign and self-limiting process in the majority of children. Severe life-threatening hemorrhages, including intracranial, develop rarely. Risk factors predisposing for development of severe hemorrhagic complications have not been determined. In order to decrease the severity of neurological consequences and mortality in intracranial hemorrhages, timely combined urgent therapy is neсessary. There are four clinical cases of intracranial hemorrhage in immune thrombocytopenia in children with different outcomes in this article. The parents of the patients agreed to use the information, including photos of children, in scientific research and publications.
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 × 10 ⁹ /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.
Introduction
In recent years, there have been changes in the management of patients with primary immune thrombocytopenia. In this study, a review is presented of the characteristics and outcomes of children with primary immune thrombocytopenia in a children’s hospital (Hospital Infantil Niño Jesús). Moreover, an analysis is made of the changes in the care of these patients diagnosed before and after 2011, when new guidelines were published by the Spanish Society of Paediatric Haematology Oncology (SEHOP).
Material and methods
Data from a cohort of primary immune thrombocytopenia patients followed up in this hospital have been retrospectively reviewed. The statistical package used for the analysis was SPSS Statistics 22.0 (IBM Corp., Chicago, IL, USA).
Results
A review is presented on the clinical data from 235 paediatric patients diagnosed with primary immune thrombocytopenia. It was observed that some features at diagnosis, such as age younger than five years and a previous history of infection, influenced the probability of cure. Regarding the changes in the management of patients since 2011, the steroid doses received during the first month and the first year, and the number of days corresponding to the patient’s first admission have both significantly decreased. Splenectomies were also significantly reduced.
Conclusions
Since 2011, there have been changes in the medical care of our primary immune thrombocytopenia patients: they receive lower doses of steroids, they stay fewer days in the hospital, and the number of splenectomies has decreased without increasing bleeding or worsening the clinical evolution. Furthermore, it was observed that age younger than 5 years and a history of infection prior to diagnosis were related to higher chances of recovery.
The disease course in a young girl with chronic immune thrombocytopenia (ITP) at the initial age of 19 months, treated with eltrombopag, was evaluated retrospectively and is presented as a case record and discussed against the background of the available literature. A stable response and reduction in clinical symptoms, over several years and without frequent dose changes, was achieved. Bleeding symptoms were mild to moderate and occurred particularly frequently in combination with low platelet counts. Raising the platelet count, in turn, was accompanied by a decreased bleeding tendency. Eltrombopag was tolerated well. No new safety signals were observed during the treatment. Based on a follow-up of more than 2.5 years, our case confirms that a child with chronic ITP can benefit from treatment with eltrombopag in the regular care setting. We assume that early treatment with a thrombopoietin receptor agonist could save many children from repeated and lengthy hospitalizations with intravenous immunoglobulins and prolonged administration of corticosteroids.
Thrombocytopenia may result from many causes. Decreased production and decreased survival of circulating platelets due to immune mechanisms are the subject of this chapter. Hemorrhagic risk is typically milder than commonly believed while risks from various treatments can be significant; thus, an enhanced tolerance of the thrombocytopenia in those failing to achieve a remission is rational. The choice of therapeutic interventions depends on the goals of treatment, and can include remission induction or brief elevations of the platelet count at times of trauma, surgery, or other invasive procedures.
Resumen
Introducción
En los últimos años se han experimentado cambios en el manejo de los pacientes con trombocitopenia inmune primaria. En este estudio se revisan las características de los pacientes con trombocitopenia inmune primaria del Hospital Infantil Universitario Niño Jesús y su evolución. Además, analizamos los cambios en el abordaje de los pacientes diagnosticados antes y después de 2011, año en el que se publicó la guía de la Sociedad Española de Pediatría.
Material y métodos
Se han revisado retrospectivamente los datos de pacientes con trombocitopenia inmune primaria en seguimiento en nuestro hospital desde el año 2000. El paquete estadístico utilizado para el análisis fue SPSS Statistics 22.0 (IBM Corp, Chicago, IL, EE.UU.).
Resultados
Se han revisado 235 pacientes pediátricos con trombocitopenia inmune primaria, observando que algunas características al diagnóstico, como la edad menor de 5 años y los antecedentes previos de infección, pueden influir en la probabilidad de recuperación. Con respecto al cambio de manejo de los pacientes, a partir de 2011 las dosis de esteroides recibidas durante el primer mes y el primer año se han reducido de forma significativa, así como el número de días del primer ingreso, pasando de 5 a 3 días. Las esplenectomías también se han reducido significativamente.
Conclusiones
Desde el año 2011 se han producido cambios en el abordaje de nuestros pacientes: reciben una menor dosis de esteroides, permanecen menos días ingresados y se ha reducido el número de esplenectomías sin aumentar los sangrados y sin disminuir la tasa de respuestas. Además, observamos que la edad menor de 5 años y el antecedente de infección previa al diagnóstico están relacionados con una mayor tasa de recuperación.
Immune thrombocytopenia (ITP) is characterized by a quantitative platelet defect due to autoantibodies directed against platelet surface antigens. Childhood ITP generally follows a viral illness. Diagnosis is made by a thorough history, physical examination, complete blood count (CBC) evaluation, and peripheral smear review to rule out other diagnoses. Additional laboratory testing is usually not necessary but may be done if the clinical scenario points toward a secondary cause for ITP. For mild bleeding, defined as cutaneous bleeding only, observation along with parental education is sufficient. Medical interventions are recommended in case of mucosal bleeding, parental anxiety, or high activity level of the child. Serious, life-threatening hemorrhagic events are rare in childhood ITP. In an office setting, pediatricians can manage ITP with serial CBC evaluations and physical examinations to rule out major bleeding symptoms.
Immune thrombocytopenia (ITP) is an autoimmune condition defined as an isolated platelet count of <100,000/microL with a normal white blood cell count and hemoglobin concentration in the absence of identifiable and specific precipitants. ITP in adolescents is similar to ITP in adults and children in terms of diagnosis and presentation. The clinical course is a hybrid, with more patients requiring therapy, and many patients eventually achieving remission. Therapy is guided by bleeding symptoms, rather than absolute platelet counts, but also by prophylaxis against bleeding, given the increased physical activity in this age group. Careful attention should be paid to females with heavy menstrual bleeding. Lastly, the psychosocial aspects of care for patients in this vulnerable age group must be considered, with attention to aspects of independence and shared decision making.
Immune thrombocytopenia (ITP) is a potential presentation of COVID-19. Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) viral testing should be considered in these patients to allow for appropriate hospital triaging and isolation to limit community spread and health care worker infection during epidemics or pandemics. ITP is characterized by isolated thrombocytopenia. Approximately two-thirds of children with primary ITP have a history of a viral infection during the previous month.1,2 Viruses commonly identified as triggers include cytomegalovirus, hepatitis C, herpes, varicella zoster, Epstein-Barr, influenza, and HIV.3-7 In this case report, we describe the first documented case of a pediatric patient with ITP who tested positive for SARS-CoV-2. This case raises awareness of ITP as a possible pediatric presentation of coronavirus disease.
Childhood chronic immune thrombocytopenic purpura (cITP) is a rare disease. In severe cases, there is no evidence for the optimal therapeutic strategy. Our aim was to describe the real‐life management of non‐selected children with cITP at diagnosis. Since 2004, patients less than 18 years old with cITP have been enrolled in the national prospective cohort, OBS’CEREVANCE. From 1990 to 2014, in 29 centres, 392 children were diagnosed with cITP. With a median follow‐up of six years (2·0–25), 45% did not need second‐line therapy, and 55% (n = 217) received one or more second lines, mainly splenectomy (n = 108), hydroxychloroquine (n = 61), rituximab (n = 61) or azathioprine (n = 40). The overall five‐year further second‐line treatment‐free survival was 56% [95% CI 49·5–64.1]. The use of splenectomy significantly decreased over time. Hydroxychloroquine was administered to children with positive antinuclear antibodies, more frequently older and girls, and reached 55% efficacy. None of the patients died. Ten years after the initial diagnosis, 55% of the 56 followed children had achieved complete remission. Children with cITP do not need second‐line treatments in 45% of cases. Basing the treatment decision on the pathophysiological pathways is challenging, as illustrated by ITP patients with positive antinuclear antibodies treated with hydroxychloroquine.
Background:
Pediatric inherited Thrombocytopenia, also known as a deficiency of platelets in children, is caused by genetic factors and is hard to obtain effective treatment. Thus, it is necessary to identify possible genetic variants responsible for the thrombocytopenia.
Methods:
The whole exome sequencing (WES) was used to detect genetic variants in two members of a thrombocytopenia family of Miao ethnic group. Multiple in silico analyses were performed to evaluate the effects of the novel missense variants.
Results:
Finally, a novel variant (chr19: g.15170364G>A) in NOTCH3 gene was found and confirmed with the Sanger sequencing, which could result in R1694Q substitution in the protein. This variant was consistently suggested to be damaging by the SIFT, PolyPhen and Mutation Taster. Through building the 3D model of the key region of NOTCH3 protein and performing the structure simulation, we found that 1) this variant affected the 3D structure model with the RMSD =0.46 between wild type and mutant type. 2) this variant caused the protein reduce the solvent accessible surface area by 421 Å2 . 3) compared with the wild type protein, the mutant protein had less two amino acids to maintain protein stability.
Conclusion:
A novel damaging variant in NOTCH3 gene was identified in a thrombocytopenia family to decrease the stability of NOTCH3, which may help the prognosis and therapy of inherited Thrombocytopenia.
Background:
This report illustrates the importance of a detailed history and physical exam and careful analysis of hematologic parameters when diagnosing ITP. This case demonstrates that even with subtle deviations from typical ITP findings one must promptly reevaluate the diagnosis. This case also highlights the importance of peripheral smear review by an expert in pediatric hematopathology.
Case presentation:
A previously healthy 10 year-old Asian boy presented with 2 months of easy bruising. Review of systems was negative for any constitutional symptoms. On examination, he appeared well but had numerous large ecchymoses. He had no appreciable lymphadenopathy or splenomegaly. The liver was palpable 1.5 cm below the costal margin. A complete blood count (CBC) showed: platelets = 17 × 109/L, hemoglobin = 128 g/L, white blood cell count = 5.43 × 109/L, and neutrophils = 1.63 × 109/L. A blood smear was reported as normal. Urate was 370 umol/L and lactate dehydrogenase (LDH) was 803 U/L. The child was admitted with a presumptive diagnosis of immune thrombocytopenic purpura (ITP) and treated with intravenous immunoglobulin. The following day, the blood smear was reviewed by a hematopathologist who identified blasts. A bone marrow aspiration (BMA) confirmed the diagnosis of precursor B-cell acute lymphoblastic leukemia.
Conclusion:
In children presenting with suspected ITP, leukemia should always be considered. A BMA was historically performed on all patients with presumed ITP to rule out leukemia. In 2011, the American Society of Hematology (ASH) stopped recommending routine BMA in patients suspected of having ITP. ASH advises in cases with unusual findings on history, physical examination or CBC, it is reasonable to perform a BMA. Our patient had mild hepatomegaly, which may have qualified him for a BMA. He also had an elevated LDH and urate, which are not listed as criteria for BMA by ASH but were considered atypical for ITP by the clinical team. A literature search did not reveal any primary data assessing these markers. While corticosteroids are a first line treatment in ITP, they must be reserved for when clinicians are confident that the patient does not have leukemia. Steroid administration prior to diagnosing leukemia results in delayed diagnosis and may increase the risk of complications and decrease survival.
Background : : Immune thrombocytopenic purpura (ITP) in children less than one year of age is less well characterized compared to ITP in toddlers and school-age children. Since children of different ages may have differing clinical courses, better delineation of the natural history of ITP in infants is needed.
Methods : : We retrospectively reviewed the admission records of 248 consecutive pediatric patients between 1 month and 15 years of age who were admitted and treated for acute ITP at Pusan National University Children’s Hospital from 2009 through 2017. All patients less than 1 year of age were identified and enrolled in this study. We investigated their demographics, clinical features, laboratory examinations, response to treatment, and long-term outcomes and made a comparison to those of children aged 1 to 10 years of age.
Results : : Ninety nine infants were identified. Male to female ratio was highest in infants and decreased with age. Seventy nine (79.8%) of the 99 infant were found to be under 6 months old. The median platelet counts at diagnosis was 6×109/L. Minor bleeding (bleeding score 0-2) was significantly dominant in infant compared to older subjects. Eighty two (96.5%) out of 85 patients achieved complete remission after initial intravenous immunoglobulin (IVIG) treatment. The relapse rate after initial CR was significantly lower than older ages (P=0.003). The platelet count after IVIG treatment in infant showed more rapid response compared to older subjects (P=0.04). Follow up information at 12 months was available for 70 infants. Chronic ITP at 12 month was seen less frequently in infants than in children 1 to 10 years of age (1.4% vs. 20.2%, P
Alemtuzumab, a humanized monoclonal antibody that targets surface molecule CD52, causes rapid and complete depletion of circulating T- and B-lymphocytes through antibody-dependent cell-mediated and complement-mediated cytotoxicity. Alemtuzumab has demonstrated superior efficacy compared to subcutaneous interferon beta-1a (SC IFNB-1a) in patients with multiple sclerosis (MS). Alemtuzumab treatment causes a rare and distinct form of secondary immune thrombocytopenic purpura (ITP), characterized by delayed onset, responsiveness to conventional therapies, and prolonged remission following treatment. In phase two and three clinical trials, the incidence of ITP was higher with alemtuzumab treatment compared to the patients receiving SC IFNB-1a. Here we report a case of ITP occurring two years after the first treatment with alemtuzumab. The patient recovered completely after a timely diagnosis and adequate treatment. Rigorous patient education and careful complete blood count (CBC) monitoring by the physician are critical for early identification and treatment of this potentially fatal disorder.
Immune thrombocytopenia (ITP) is a common immune-mediated bleeding disorder in children, and intravenous immunoglobulin (IVIG) is widely used as the initial therapy of ITP. Effective predictive factors of response to IVIG in ITP are important for guiding the treatment decisions. A retrospective study was performed on 197 Chinese ITP patients, and the data of their serum interleukin (IL)-2, IL-4, IL-6, IL-10, tumor necrosis factor-α (TNF-α), interferon-γ (IFN-γ) levels, age at onset, duration of disease, white blood cell count (WBC), platelet count, and gender ratio were collected. Our results showed that ITP patients had higher IL-2, IL-6, IL-10, and IFN-γ levels than healthy children. Moreover, lower IL-4 level (<3.5 pg/ml), higher WBC (>6.37*109/L), and higher platelet count (>12 * 109/L) at diagnosis were favorable predictive factors for IVIG response in the newly diagnosed ITP. In addition, ITP patients with lower IL-10 level (<3.7 pg/ml) and older onset age (>2.84 years) were more resistant to therapy and developed to chronic ITP more easily. These findings may help guide the treatment decisions making for ITP patients.
Purpose
The pharmacology, pharmacokinetics, efficacy, safety, dosing and administration, and place in therapy of fostamatinib, a novel spleen tyrosine kinase inhibitor for the treatment of adult immune thrombocytopenia that has had an insufficient response to a previous treatment are summarized.
Summary
Fostamatinib is an oral inhibitor of spleen tyrosine kinase that is expressed on hematopoietic cells and plays a key role in the accelerated destruction of platelets through Fc-receptor activation. Fostamatinib is indicated for the treatment of adults with immune thrombocytopenia that has had an insufficient response to a previous treatment. In 2 parallel, identically designed, placebo-controlled Phase III trials, patients with persistent and chronic immune thrombocytopenia treated with fostamatinib demonstrated clinically meaningful responses in platelet counts with lower rates of moderate and severe bleeding-related adverse events. Overall, fostamatinib therapy is generally well tolerated; the most common adverse events reported in clinical trials were diarrhea, nausea, hypertension, liver function test elevations, and infection. Being primarily metabolized through the CYP3A4 pathway, fostamatinib is subject to drug–drug interactions and concomitant administration with strong CYP3A4 inhibitors or inducers can affect fostamatinib exposure.
Conclusion
Fostamatinib is a first-in-class spleen tyrosine kinase inhibitor approved for the treatment of adults with immune thrombocytopenia that has had an insufficient response to a previous treatment.
Immune thrombocytopenic purpura (ITP) is a common cause of symptomatic thrombocytopenia in children, most of whom present with cutaneous and mucosal bleeding. Complications, such as intracranial hemorrhage and occult hemorrhage from various sites, are rare, and retinal hemorrhage is exceptionally rare. Our institutional clinical practice guidelines for managing ITP in the pediatric emergency department (PED) include routine funduscopy. The aim of this retrospective case series is to provide evidence-based recommendations for a tertiary care PED work-up of ITP, with special emphasis on the guidelines for funduscopy. The medical records of all pediatric patients diagnosed with ITP over a 4-year period (2013–2016) who had a platelet count < 50,000/mm3 were retrieved and reviewed. Seventy-five patients with thrombocytopenia (platelet count < 50,000/mm3) were diagnosed as having ITP in the PED. Sixty-one (79%) of these patients underwent funduscopy and retinal hemorrhage was ruled out in all of them, indicating that retinal hemorrhage as a complication of ITP is very rare.Conclusion: Our data suggest that funduscopy should not be performed routinely on pediatric ITP patients, but rather be reserved for those who present with concurrent anemia or visual complaints.
What is Known:
• Many internal institutional protocols in Israel call for retinal hemorrhage bleeding surveillance in work up of ITP. Our study found no case of ITP with retinal bleeding.
What is New:
• Many internal institutional protocols in Israel call for retinal hemorrhage bleeding surveillance in work up of ITP. Our study found no case of ITP with retinal bleeding.
Introduction
Adverse events following immunization (AEFIs) are unwanted or unexpected health outcomes following vaccination, which may or may not be causally-linked to vaccines. AEFI reporting is important to post-marketing vaccine safety surveillance and has the potential to identify new or rare AEFIs, show increases in known AEFIs, and help to maintain public confidence in vaccine programs. Knowledge of the expected incidence (i.e. background rate) of a possible AEFI is essential to the investigation of vaccine safety signals. We selected three rarely reported AEFIs representing the spectrum of causal association with vaccines, from proven (immune thrombocytopenia [ITP]) to questioned (Kawasaki disease [KD]) to unsubstantiated (multiple sclerosis [MS]) and determined their background rates.
Methods
We extracted data on hospitalizations (CIHI Discharge Abstract Database) for ITP, KD, and MS among Ontario children for the period 2005 to 2014 from IntelliHEALTH. As ITP can be managed without hospitalization, we also extracted emergency department (ED) visits from the CIHI National Ambulatory Care Reporting System. For all conditions, we only counted the first visit and if the same child had both an ED visit and a hospitalization for ITP, only the hospitalization was included. We calculated rates by year, age group and sex using population estimates from 2005–2014, focusing on age groups within the Ontario immunization schedule around vaccine(s) of interest.
Results
Per 100,000 population, annual age-specific incidence of ITP in children age 1 to 7 years ranged from 8.9 to 12.2 and annual incidence of KD in children less than 5 years ranged from 19.1 to 32.1. Average annualized incidence of adolescent (11–17 years) MS across the study period was 0.8 per 100,000.
Discussion
Despite limitations, including lack of clinical validation, this study provides an example of how health administrative data can be used to determine background rates which may assist with interpretation of passive vaccine safety surveillance.
BACKGROUND
The incidence of immune thrombocytopenia (ITP) is not well known in Asians. The aims of this study were to survey incidences and clinical features of ITP in Taiwan.
STUDY DESIGN AND METHODS
This study identified 4855 incident ITP cases from the population‐based National Health Insurance Research Database from mid‐2006 to mid‐2013, and compared incidences, patient characteristics, and clinical manifestations of ITP by age.
RESULTS
Respective ITP incidence rates among those aged <15, 15 to 59, and ≥60 years were 4.0, 2.0, and 5.4 per 100,000 person‐years. A male predominance was noted in children, and a female predominance was found in adults. The most common causes of secondary ITP were systemic lupus erythematosus (21.8%), viral hepatitis C (16.9%), and viral hepatitis B (13.4%). The rate of secondary ITP in children was less than one fifth that in adults (4.2% vs. 23.8%). Rates of central nervous system (1.1%) and gastrointestinal tract bleeding (3.3%) were rare, with variations by age. The rate of splenectomies in children (0.4%) was only one tenth that in adults (4.1%). The disease in 25% of children and 30% of adults became persistent or chronic. A decreasing trend in the ITP incidence was found (annual percentage change, −4.9%), and it was confined to those aged >15 years.
CONCLUSION
Incidence estimates of ITP in Taiwan were close to those of Western countries, with age‐specific variations in sex ratio, comorbidity, splenectomy, secondary causes, and incidence trends. The results suggest no racial variations in ITP incidences, but a geographical difference in causes of secondary ITP.
1 Background
Immune thrombocytopenia (ITP) is an acquired immune‐mediated disorder characterized by isolated thrombocytopenia. Pediatric ITP patients are prone to develop autoantibodies such as antithyroglobulin (TG) and antithyroperoxidase (TPO), even in the absence of clinical signs of autoimmune disease. The aim of this multicenter retrospective study was to evaluate (1) the prevalence of positivity of antithyroid antibodies (TPO and TG) in a large cohort of pediatric patients with chronic ITP; (2) the role of autoimmune thyroiditis as a prognostic factor for chronicity of ITP.
2 Procedure
For this retrospective study, we collected data from patients diagnosed as affected by chronic ITP between 2011 and 2014 in six centers belonging to the Italian Association of Pediatric Haematology and Oncology (AIEOP).
3 Results
From the analysis of data, we found a significantly higher prevalence of antithyroid antibodies in children with chronic ITP (11.6%) than in the pediatric population (1.2%–1.3%).
No correlation has been found between the platelet count and the prevalence of positive antithyroid antibodies at any detection time of the study.
4 Conclusions
The results of our study demonstrated that (1) the prevalence of positivity for antithyroid antibodies (anti‐TPO and anti‐TG) in pediatric patients with chronic ITP results is significantly higher than in the pediatric population; (2) autoimmune thyroiditis does not seem to play a role as a prognostic factor for chronicity of ITP in pediatric patients.
Idiopathic thrombocytopenic purpura in children usually a self limiting disorder. It may follow a viral infection or immunisation and is caused by an inappropriate response of the immune system. About 20–30% of children will fail to remit over six months (chronic idiopathic thrombocytopenic purpura). This is more likely in older children, especially girls. The disease is reviewed with reference to diagnosis, investigation, and management options.
A prospective, population-based registration of children with immune thrombocytopenic purpura (ITP) was performed in Norway in 1996 and 1997. Ninety-two cases were identified, indicating an incidence of 5.3 per 100,000 children under 15 years. The sex ratio (female/male) was 1.2/1. Fifty-six percent presented with cutaneous signs only. The lowest platelet count was < 20 x 10(9)/L in 91%. In spite of mild bleeding symptoms, medical treatment was given in 68%, in most cases (57/63) with intravenous immunoglobulin. A total of 41/44 patients with platelet counts of < or = 5 x 10(9)/L were treated, regardless of whether they had mucous bleedings or not. Eighteen percent had platelet counts < 150 x 10(9)/L at 6 months, and 9% at 12 months following diagnosis. One patient with therapy-resistant chronic ITP died 16 months after diagnosis from an anesthesia complication related to profound epistaxis. This study shows a relatively high incidence. As in other studies, there was a tendency to treat platelet counts rather than bleeding symptoms.
A CAUSAL ASSOCIATION BETWEEN MEASLES: mumps-rubella (MMR) vaccine and idiopathic thrombocytopenic purpura (ITP) was confirmed using immunisation/hospital admission record linkage. The absolute risk within six weeks of immunisation was 1 in 22 300 doses, with two of every three cases occurring in the six week post-immunisation period being caused by MMR. Children with ITP before MMR had no vaccine associated recurrences.
Immune thrombocytopenic purpura, which may lead to bleeding, is typically caused by antibodies directed against the platelet glycoprotein IIb/IIIa complex. Since the management of the disorder is different for children and adults, the authors of this up-to-date review provide separate sections on the two age groups. Along with advances in management, they also discuss the current understanding of pathophysiology and, in particular, the way in which autoantibodies against platelets are generated.
A CAUSAL ASSOCIATION BETWEEN MEASLES—mumps-rubella (MMR) vaccine and idiopathic thrombocytopenic purpura (ITP) was confirmed using immunisation/hospital admission record linkage. The absolute risk within six weeks of immunisation was 1 in 22 300 doses, with two of every three cases occurring in the six week post-immunisation period being caused by MMR. Children with ITP before MMR had no vaccine associated recurrences.
ITP in childhood is most often of the acute, self-limited variety, with spontaneous recovery occurring within a matter of days or weeks. In many of these children, acute thrombopenic purpura follows in the wake of a viral infection. While the pathogenesis is not entirely clear, it seem probable that the platelet membrane is altered by virus or by soluble viral antigen-antibody complexes; platelets thus damaged become susceptible to rapid destruction by the RES. Management remains somewhat controversial. While almost all agree that corticosteroid should not be used in all cases of acute childhood purpura, there are still no clear-cut indications for their use, and no real evidence that they are of benefit in reducing the risk of the one rare but serious complication of childhood ITP, namely, intracranial hemorrhage (ICH). In approximately 5-10% of children, ITP ultimately proves to be of the chronic variety, and is in all probability the same condition that is seen in adults. Splenectomy is the treatment of choice, Another small subgroup of children have ITP of the recurrent acute variety; there is some evidence that this entity may also have an autoimmune pathogenesis. Infants born to mothers who have (or have had) ITP often manifest thrombopenia, with or without purpura and other bleeding. While this is generally a benign, self-limited process, requiring no treatment, ICH occurs in a small but significant number of affected infants and probably results from head trauma during delivery.
We studied the extent to which patient characteristics influenced outcome in childhood idiopathic thrombocytopenic purpura in a historical cohort of 289 children over a 20 year period (1968-87). Outcome was classified as acute or chronic depending on whether the platelet count had returned to normal (150 X 10(9)/l) by six months after diagnosis. Fifty three cases (18%) had chronic idiopathic thrombocytopenic purpura. The likelihood of chronic disease was determined by logistic regression analysis of five patient variables: age, sex, season of onset of symptoms, history of recent viral illness, and duration of symptoms at presentation. A history of symptoms of greater than 14 days at presentation, adjusted for the other variables, was strongly predictive of chronic idiopathic thrombocytopenic purpura; the other variables did not significantly affect outcome. At 28 days after diagnosis 138 (47%) of the study cohort had normal platelet counts. Children whose platelet counts were less than 150 X 10(9)/l had a threefold risk of progressing to chronic idiopathic thrombocytopenic purpura, which increased to fivefold if counts were less than 50 X 10(9)/l. Two thirds of patients in the chronic group, irrespective of treatment, remained thrombocytopenic two years after diagnosis. We conclude that a history of symptoms for greater than two weeks at presentation is strongly predictive of chronic idiopathic thrombocytopenic purpura. If platelet counts are subnormal 28 days after diagnosis the risk of chronic idiopathic thrombocytopenic purpura is increased with prolonged thrombocytopenia being very likely if platelet counts remain low three months after diagnosis.
In a 10 year study of children with idiopathic thrombocytopenic purpura, it was found that most of them recovered spontaneously, some as long as 31/2 years after the onset. Corticosteroid therapy failed to influence the course, duration, or prognosis. In children with long-standing symptomatic disease, splenectomy was usually curative. A longer course was associated with insidious onset and/or when no preceding illness was recorded. Prognosis was not related to initial severity of presentation, enlargement of liver or spleen, bone marrow eosinophilia, or increased numbers of megakaryocytes.
One hundred and eighty one children with thrombocytopenia for which no cause could be found have been studied. One patient died with severe bleeding possibly from disseminated intravascular coagulation and one developed cerebral haemorrhage, both within two weeks of onset. Ninety one per cent of the 135 with acute disease but only 36% of those with chronic disease remitted spontaneously. Twenty per cent of spontaneous remission occurred more than one year after onset. Six patients have run an intermittent course for 10 to 20 years. Four patients have had symptomless thrombocytopenia for between 10 and 30 years. Of 32 children treated by splenectomy 24 maintained normal platelet values thereafter. One boy died from pneumococcal septicaemia two years after splenectomy but he had not received prophylactic penicillin. One hundred and fifty eight patients were followed up 3 to 37 years (mean 16.4 years) after onset. None who recovered spontaneously or after splenectomy had had further bleeding problems. No patient nor immediate relative had developed other autoimmune disease. We consider that a short course of corticosteroids immediately after diagnosis is justified in all cases even though we cannot produce proof that it influences the course of the disease. We do not accept any place for long term immunosuppressant treatment.
Between 1975 and 1992 450 children with idiopathic thrombocytopenic purpura (ITP) were diagnosed, and of those 100 (22%) developed the chronic form of the disease. Approximately half the patients with chronic ITP presented with mild to moderate hemorrhagic manifestations at the onset of purpura (30 cases) and/or later during the course of the disease (25 cases). The incidence of intracranial hemorrhage was 1%, and the mortality rate due to overwhelming septicemia after splenectomy was also 1%. Overall one-third of the patients received no therapy; two-thirds of them went into spontaneous remission within 8 months to 8 years from the onset of ITP. Steroids given in conventional or high doses (51 cases) achieved a transient (if any) rise in platelet count, but in no case were steroids curative. Remission related to intravenous immune globulin (IVIG) therapy was noticed in 38.5% of the children (10 of 26) after variable courses. The response rate to splenectomy was 95.0%. Ultimately the long-term outcome in children with chronic ITP was as follows: remission, 58 cases (spontaneous, 30; after IVIG therapy, 10; after splenectomy, 18); hemostatic platelet values, 22 cases (spontaneous, 16; after IVIG, 5; after splenectomy, 1). Thirteen children were lost in follow-up, and 7 remain thrombocytopenic but asymptomatic. These data indicate that chronic ITP in childhood runs a benign course in most cases and may remit with or without therapy even several years from onset. Therefore, therapeutic intervention has to be individualized, and splenectomy, which is not always safe, should be reserved for problematic cases that fail to respond to conventional therapeutic modalities.
Fifty-three children, aged 7 months to 14.4 years and with typical acute immune thrombocytopenic purpura and platelet counts < or = 20 10(9)/L, were randomly assigned to receive intravenously administered immune globulin G (IVIG), 1 gm/kg per day for 2 consecutive days (n = 19); orally administered prednisone, starting at a dose of 4 mg/kg per day, with tapering and discontinuation of corticosteroids by day 21 (n = 18); or no therapy (n = 16). Both IVIG and prednisone resulted in significantly fewer days with platelet counts < or = 20 x 10(9)/L in comparison with no therapy (median, 1 and 2 days vs 4 days; corresponding ranges, 1 to 20 and 1 to 11 days vs 1 to 132 days; p < 0.01). Reversal of clinically important thrombocytopenia assessed by the number of days taken to achieve a platelet count of > or = 50 x 10(9)/L was significantly faster in children randomly assigned to receive IVIG (median, 2 days; range, 1 to 34 days) than in those receiving prednisone (median, 4 days; range, 2 to 13 days; p < 0.001) or no therapy (median, 16 days; range, 2 to 132 days; p < 0.001). Because the risk of intracranial hemorrhage in children with acute immune thrombocytopenic purpura is highest in the group with severe thrombocytopenia, and appears to be restricted to children with platelet counts < or = 20 x 10(9)/L, these results support the use of IVIG or high doses of prednisone as initial therapy in children with acute immune thrombocytopenic purpura and severe thrombocytopenia (platelet counts < or = 20 x 10(9)/L).
An acute thrombocytopenic purpura developed shortly after measles-mumps-rubella vaccination in 23 of approximately 700,000 children immunized over a period of seven years. The mean interval from inoculation to the onset of purpura was 19 days. Bone marrow aspirates obtained from 13 patients showed increased or normal amounts of megakaryocytes. Platelet survival time was markedly shortened in the two patients studied. Fifteen patients recovered (the platelet count exceeded 100 x 10(9)/l) in one month, five in two months and two in six months. Increase in platelet-associated immunoglobulin was detected in 10 of 15 patients. Circulating antiplatelet autoantibodies (AAb) against glycoprotein IIb/IIIa were detected in 5 of 15 patients. The findings are compatible with an autoimmune mechanism triggered by immune response to measles-mumps-rubella vaccination. As evaluated by the clinical course and the presence of AAb, post-vaccination thrombocytopenic purpura appears to be indistinguishable from childhood acute idiopathic thrombocytopenic purpura.
The frequency and treatment of children with chronic idiopathic thrombocytopenic purpura in Sweden were characterized using a national enquiry based on a questionnaire. Seventy-five children diagnosed as having chronic idiopathic thrombocytopenic purpura on 1 September 1993 were identified. The prevalence in children between 0.5 and 15.5 years of age was calculated to be 4.6/100,000. The median age at the time of diagnosis was 5 years and the male/female ratio was 1:1.2. Almost half of the patients (43%) were not treated at all during the disease. Steroids (43%) and intravenous immunoglobulin (25%) were most commonly used. Only two children were splenectomized.
In this retrospective study of 20 years, 78 children with chronic idiopathic thrombocytopenic purpura (ITP) were analyzed. Patients were followed for 1-17 years (median 2.7 years). Every application that required therapy was accepted as an "attack." Seventy-eight patients received therapy in 236 attacks. Immediate platelet responses to high-dose methylprednisolone (HDMP), prednisone, and splenectomy were 69.3% (in 53 patients), 48.3% (in 35 patients), and 84.6% (in 29 patients) of attacks, respectively. Because 31 patients were lost to follow-up, the rate of remission was calculated on the basis of 47 patients. The remission rates for patients who underwent remission spontaneously, after steroid therapy, and after splenectomy were 29.78, 6.38, and 14.89%, respectively. Of 78 adolescent patients, 11.5% had intracranial hemorrhage (ICH), being after splenectomy. One patient died because of ICH. These data indicate that chronic ITP is still a serious problem during adolescence and splenectomy still seems to be a current choice of therapy.
Guidelines for management of acute immune thrombocytopenic purpura (ITP) in childhood were published in 1992. Regional audit in 1995 showed substantial variation in clinical practice not related to clinical differences in patient groups, which indicated a need for national audit.
Individuals aged from birth to their 16th birthday newly presenting with ITP were identified over 14 months by regular mailing of paediatricians and haematologists for case notification. Information was obtained from follow-up by a detailed questionnaire.
ITP was clinically mild and benign in 323 (76%) of 427 cases, including 181 (70%) of 260 cases with platelet counts below 10 x 10(9)/L. There were no deaths or intracranial haemorrhages. There was a substantial discrepancy between clinical practice and published guidelines: many children were admitted to hospital and received treatment unnecessarily; there was overuse of intravenous immunoglobulin (IVIg) as first-line therapy (94 children); children received steroids without marrow examination; and there was inappropriate use of platelet transfusions (41 with mild or moderate disease).
Our results indicate a need for change in practice.
The concepts of the pathological mechanisms in childhood idiopathic thrombocytopenic purpura (ITP) have, to a great extent, been based on clinical experience and on data generated in adults. Studies performed in children have demonstrated that platelet antigen-specific autoantibodies are present in chronic ITP and, to a lesser extent, in acute ITP. It is, however, likely that the mechanisms initiating the production of autoantibodies are different in the two entities. In acute ITP, production of autoantibodies and immune complexes is probably linked to a transient antiviral immune response. Chronic ITP in children is an autoimmune process which eventually is reversible in many cases. The initiating factors, as in other autoimmune disorders, are yet to be elucidated.
Idiopathic thrombocytopenic purpura (ITP) is the most common acquired bleeding disorder encountered by pediatricians. Most children with ITP have minimal bleeding and complete platelet count recovery within weeks to months. Therapy for ITP has ranged from close observation without medical intervention to aggressive management with corticosteroids, intravenous immunoglobulin G, or anti-D immune globulin. The topic of ITP has incited great debate among practitioners, and this debate prompted the development of ITP practice guidelines by the British Paediatric Haematology Group in 1992 and by the American Society of Hematology in 1996. A better understanding of the clinical course of, risk for significant bleeding in, and optimal evaluation and therapy of childhood ITP will require carefully designed, multicenter, clinical trials.
Idiopathic thrombocytopenic purpura in children usually a self limiting disorder. It may follow a viral infection or immunisation and is caused by an inappropriate response of the immune system. About 20-30% of children will fail to remit over six months (chronic idiopathic thrombocytopenic purpura). This is more likely in older children, especially girls. The disease is reviewed with reference to diagnosis, investigation, and management options.
Little is known about the influence of environmental and ethnic factors on the epidemiology of immune thrombocytopenic purpura (ITP). Therefore we compared the initial presentation and condition after 6 mo in 90 Vietnamese and 89 German and Swiss children with newly diagnosed ITP. Data from the two cohorts were collected within the same time period. No differences in age and sex were observed between the Asian and European cohorts, but significant differences between initial platelet count, the occurrence of dry versus wet bleeding symptoms, and infection preceding the onset of ITP were found. Children who had chronic ITP also differed with respect to platelet count and postinfectious state, but not initial bleeding type. In addition, chronic ITP occurred more often than expected with a male to female ratio of 1.2 in Vietnam and 2 in Germany and Switzerland. The data support the potential influence of environmental or ethnic factors on the different aspects of ITP, and point to the need for further epidemiologic investigations.
The management of childhood acute idiopathic thrombocytopenic purpura is controversial, with recent guidelines highlighting the lack of suitable evidence upon which to base management decisions. Three European centers have used an expectant policy and results over the past decade demonstrate that this is safe and convenient for the majority of children. Adequate parental education about the condition from an experienced specialist is essential, together with open access for children should they develop any problems. A clinical stratification of such patients must be incorporated into any future trials, together with quality of life assessment to discover the impact of restrictions on lifestyle, particularly in adolescents with chronic ITP who may need a different approach.
Treatment of acute childhood immune thrombocytopenia (ITP) is controversial. For information on the present situation in Germany, a retrospective and a prospective survey were carried out. In the retrospective survey, questionnaires were sent to all German pediatric hospitals asking about local policies for handling ITP and whether in the preceding year (starting on October 1995) death or ICH had occurred; 86% answered. In the prospective survey, 94% responded to the mailings ("have you seen a case of ITP?") sent in monthly intervals between October 1, 1996 and September 30, 1997; 89% of the questionnaires were retrieved. In the retrospective survey, no deaths and no ICH were reported. If only mild bleedings, such as skin bleeds alone (or additional mild mucous membrane bleeding) were present, 20.5% (26.4%) preferred the "watchful waiting" regimen (supportive care), irrespective of the platelet count; 79.5% (73.6%) would treat if the platelet counts were <5 x 10(9)/L, 73.5% (67.9%) if < 10, 35.9% (33.6%) if < 20, and 4.2% (2.6%) if <30. Of the treaters, 50.5% would prefer immunoglobulins (Ig), 24.4% glucocorticosteroids (GC), and 20.5% GC and/or Ig. Generally, a rise in platelets, most frequently >50 x 10(9)/L was considered as therapeutic success. In the prospective survey, from the reported 323 children an annual incidence of 2.16 per 100,000 children was calculated. The incidence depended on age and gender, being highest for boys younger than 2 years with 5.8 (girls 3.42) and low with 0.44 for boys (girls 0.89) older than l4 years. About 60% of the patients had a preceding infection. Although 83% had a platelet count <20 x 10(9)/L (56% <10 x 10(9)/L), almost all (97.5%) had only mild bleeding symptoms; 2.5% had serious bleeding symptoms requiring blood transfusion or nasal packing, none had ICH, and no death was reported. The mean platelet count on admission was 11.348 (lowest count 8.253) x 10(9)/L. Sixty-one percent received Ig, 19% GC (both either alone or as first choice), 6% Ig plus GC, and 14% no treatment. Side effects were reported in 22% of the children treated with Ig. The retrospective survey mirrored the uncertainty in regard to treatment. The prospective survey provided new aspects on incidence, age, and gender distribution. Although almost all patients had only mild bleeding symptoms, most received Ig and/or GC. The decision to treat depended mainly on the platelet count. From these surveys, conclusions about the effectiveness of treatment cannot be drawn. Recommendations based primarily on platelet counts must be reconsidered.
Diagnosis and management of idiopathic thrombocytopenic purpura (ITP) have been based primarily on expert opinion and practice guidelines rather than on evidence. We have used a registry to prospectively survey the presenting features and the diagnostic evaluation and management practices used for children with ITP worldwide.
We used the Intercontinental Childhood ITP Registry which had been widely advertised. 209 physicians from 136 institutions in 38 countries participated by submitting data for each of their newly diagnosed patients. Data from 2031 children with ITP was registered between June, 1997, and May, 2000, and we analysed 6-month follow-up data from 1496 children.
There was a peak in occurrence of childhood ITP during spring and a nadir in the autumn. Mean initial platelet count was 15.4x10(9)/L (SD 19.7). 1447 (73%) of 1976 children were admitted to hospital. Initial management consisted of no drug treatment in 612 (31%), intravenous immunoglobulin in 576 (29%), corticosteroids in 651 (33%), or both in 137 (7%) patients. Intracranial haemorrhage was reported in two patients.
The variable approaches to management of childhood ITP demonstrate the need for prospective clinical trials, which should be feasible within such a study group.
To retrospectively review our institutional experience of adolescents with idiopathic thrombocytopenic purpura (ITP).
Medical record review of all patients diagnosed with ITP between the ages of 10 and 18 years seen at our center from January 1976 to March 2000.
Data were collected from 126 patients. Of the evaluable 110 cases, 63 (57%) satisfied the criteria for chronic ITP, 30 (27%) for acute ITP, and 17 (15%) were uncertain. Sex distribution and mean ages were similar in all 3 groups. Platelet count at presentation was higher in patients with chronic ITP. Splenectomy was performed in 24 patients, with 17 (77%) of 22 having normal platelet counts at last follow-up. Outcome for the nonsplenectomized patients with chronic ITP included normalization of platelet count (n = 4), minimal or no bleeding without treatment (n = 29), treatment for ongoing symptoms (n = 5), and unknown (n = 1). Two patients died, 1 from intracranial hemorrhage and 1 from Escherichia coli sepsis and pulmonary hemorrhage.
Patients 10 to 18 years of age with ITP are more likely than younger children to have chronic disease. Many patients with ITP recover without drug therapy or need for splenectomy. ITP in adolescents shares features of both childhood and adult ITP.
Clinical course and treatment outcome of childhood chronic ITP are quite variable in the literature. We report in the current paper our observation on the clinical behavior of chronic ITP in Chinese children.
We performed a retrospective review (Jan. 1990 to Dec. 2000) of children having low platelet count (plt <150 x 10(9)/L) for more than 6 months without identifiable cause. The indication for treatment was plt < or =20 x 10(9)/L. Remission is defined as plt > or =150 x 10(9)/L.
Thirty-four children were identified within these 11 years. Their median age at diagnosis was 6.7 years (range from 0.4 to 16.8 years). The M:F ratio was 16:18. Bone marrow aspiration was performed in 30/34 cases. The median plt count at presentation was 24 x 10(9)/L (range 2 to 135 x 10(9)/L). Fourteen of 34 (41%) children eventually achieved durable remission. The chance of remission at 5 years was 66.62% with a median follow-up time of 5.86 years (range 0.72 to 10.41 years). Concerning therapy, 17/34 (50%) required no treatment while for the remaining 17, treatment included steroid (n = 16), IVIG (n = 7) or splenectomy (n = 3). In spite of temporary improvement in most, treatment induced prolonged complete remission (plt >150 x 10(9)/L) in only 2 patients. Twenty of 31 tested had abnormal immune marker(s) at presentation but none evolved into specific autoimmune disease later on. There was no correlation between the remission status, response to treatment, and the presence of autoimmune markers.
About half of our chronic ITP patients achieved remission within 5 years. Medical treatment does not seem to alter the natural course of the disease but induced a transient response in most cases. Positive autoimmune markers are common among chronic ITP patients and have no significance in predicting outcome.
To determine the duration of the risk period with platelet counts <20 x 10(9)/L and the frequency of bleeding episodes in unselected children with idiopathic thrombocytopenic purpura (ITP).
We established a registry for patients with newly diagnosed ITP in the five Nordic countries, enrolling children aged 0 to 14 years with platelet counts <30 x 10(9)/L. Treatment centers prospectively reported presenting features, management details, and disease-related events during the first six months after diagnosis.
At presentation (n=501), more than half of the children had a platelet count <10 x 10(9)/L, but only 15 (3.0%) had a hemorrhage requiring blood transfusion. During follow-up of 409 patients, thrombocytopenia resolved uneventfully in 277. A risk period was present in 376 cases. Among 283 with self-limiting ITP, 26 were at risk >1 month and 25 had 30 events. Among 93 patients with chronic ITP, 73 were at risk >1 month and 44 had 111 events. Events occurred with an average frequency of 0.39 per month at risk. Life-threatening hemorrhages did not occur in the first six months after diagnosis.
Most children with ITP are at risk for serious bleeding for less than one month. Continuing severe thrombocytopenia is associated with little morbidity, bleeding episodes being infrequent and very rarely serious.
To analyze prospectively the impact of age at diagnosis in childhood idiopathic thrombocytopenic purpura (ITP).
International registry from June 1997 to May 2001, with analysis of data from baseline and 6-month-follow-up questionnaires.
Data from 2540 patients were analyzed, including 203 infants (7.6%), 1860 children > or =1 to <10 years of age (69.1%), and 477 children and adolescents between > or =10 and <16 years of age (17.7%). The mean platelet count at diagnosis was similar in all three groups, as was the percentage of patients with initial platelet count <20x10(9)/L. The male/female ratio was highest in infants and decreased with age (P=.009). Immunoglobulin therapy was used more often in infants and corticosteroids in patients > or =10 years of age. Follow-up information at 6 months was available for 1742 children (68.6%). Chronic ITP was seen less frequently in infants (23.1%) than in children >10 years of age (47.3%, P<.0001). Intracranial hemorrhage occurred in 3 of 1742 children during the first 6 months after the diagnosis of ITP.
Pediatric patients with ITP from infancy to adolescence exhibit heterogeneity in clinical, demographic, and treatment factors.
To develop an instrument to allow semiquantitative assessment of hemorrhage in children with idiopathic thrombocytopenic purpura (ITP).
Bleeding severity was graded on a scale of 0 to 4 in 4 different sites (overall, oral, epistaxis, and skin) on the basis of history during the previous 24 hours and physical examination.
Children with ITP (n = 54) were assessed on 109 different occasions by multiple observers, including 81 measurements by one of the authors. Grade of bleeding correlated inversely with platelet count. Grade 3 or 4 hemorrhage was infrequently encountered except involving the skin, where assessment was difficult. Grade 4 mucosal or internal hemorrhage was noted in 7 patients; none had life-threatening or fatal bleeding. Interrater agreement in grading of overall and mouth bleeding and epistaxis was acceptable.
We conclude that scoring of hemorrhage is possible in children with ITP and that the grade of hemorrhage may represent a clinically meaningful end point in future studies.
Idiopathic thrombocytopenic purpura Arch Dis Child
- Phb Bolton-Maggs
- Bolton-Maggs PHB
Intracranial haemorrhage in idiopathic thrombocytopenic purpura
- Lilleyman JS on behalf of the Paediatric Haematology Forum of the British Society for Haematology
Seventeen years of experience with chronic idiopathic thrombocytopenic purpura in childhood
- Aronis
- Platokouki
- Mitsiki
- Haidus
- A Constantopoulos
- Aronis S
Guidelines for the investigation and management of idiopathic thrombocytopenic purpura in adults, children and in pregnancy
- Provan
- Newland
- Norfolk
- Bolton-Maggs
- Lilleyman
- Greer
- Provan D
A prospective, randomized trial of high-dose intravenous immune globulin G therapy, oral prednisone therapy, and no therapy in childhood acute immune thrombocytopenic purpura
- Blanchette
- Andrew Luke
- Sommerville-Nielsen
- Barnard
- Veber
- Blanchette VS