Childhood Idiopathic Thrombocytopenic Purpura Research Articles

La prise en charge du purpura thrombopénique idiopathique en phase initiale : enquête auprès des membres de la Société française d'hématologie et d'immunologie pédiatrique (SHIP)

Aim of the study The purpose of this study was to report in acute childhood idiopathic thrombocytopenic purpura (ITP) the current practices of French paediatric hematologists and to compare them to recent publications of American and British teams. Method A questionnaire was sent online to the members of the French Society of Pediatric Hematology/Immunology (SHIP). This questionnaire, adapted from a similar american study conducted in 2001, asked 16 questions based on the clinical presentation of a 5-year-old boy referred for an acute ITP. Results 59/123 SHIP members responded to the survey. In response to question regarding initial treatment, 86% of physicians would be given active treatments and only 9% would rarely or never administer any drug. When asked which agent would be used in case of treatment, 68% would choose to prescribe intravenous immunoglobulins and 32% corticosteroids, nobody recommended the use of anti-D immunoglobulins. Furthermore, 83% would usually hospitalize such a child. Conclusion Finally, this study allowed us to update the current French management of treating pediatric ITP which is almost comparable among this subset of pediatric hematologists, but showed some discrepancies comparatively to the American and British studies.

Survey of childhood idiopathic thrombocytopenic purpura in Aomori prefecture between 2001and 2004

Survey of childhood idiopathic thrombocytopenic purpura in Aomori prefecture between 2001and 2004

Splenectomy in children with idiopathic thrombocytopenic purpura: A prospective study of 134 children from the Intercontinental Childhood ITP Study Group

Splenectomy is an effective procedure for children and adults with severe or refractory idiopathic thrombocytopenic purpura (ITP). Data regarding pediatric patients are limited. Sixty-eight Intercontinental Childhood ITP Study Group (ICIS) investigators from 57 institutions in 25 countries participated in a splenectomy registry. Data from 153 patients were submitted, of whom 134 had a splenectomy and were analyzed. The median age at splenectomy was 11.8 (2.7-20.7) years. The median postsplenectomy follow-up was 2.0 (0.1-4.5) years. Pre-splenectomy vaccination was not administered in 21 children (15.7%). Open and laparoscopic splenectomy procedures were performed in 67 and 65 evaluable children, respectively. Surgical technique was not reported in two children. Overall immediate platelet response to splenectomy was achieved in 113 patients (86.3%). Eighty percent of responders maintained their status of response during the following 4 years. Older age, longer duration of ITP, and male gender correlated with a complete response. Post-splenectomy sepsis was reported in seven patients without lethal outcome, although sepsis might be differently defined at participating institutions. Splenectomy is effective in children with ITP. Management varies greatly in different institutions. These Registry data may serve as a basis for future clinical trials to assess the indication and timing of splenectomy.

Outcome Measures in Childhood Idiopathic Thrombocytopenic Purpura: Relationship of Bleeding Severity, Quality of Life, and Platelet Count.

Idiopathic thrombocytopenic purpura (ITP) is one of the most common disorders requiring the attention of a pediatric hematologist. The most feared outcome of ITP is intracranial hemorrhage (ICH), which fortunately is a rare occurrence in children. Although a rise in platelet count and presumed reduction in risk of ICH are stated therapeutic aims, it is equally important to identify and understand additional outcome measures which are subject to change in this population. These include health-related quality of life (QoL), treatment side effects, cost, and bleeding severity. A QoL questionnaire for pediatric acute and chronic ITP has recently been developed and validated. During the validation study (Pediatr Blood Cancer , 46:692, 2006), grading of hemorrhage and platelet count were also assessed. This report describes the results of a secondary data analysis using the validation study database. Our purpose was to assess the relationship between bleeding severity and QoL, previously not reported. Ninety children (mean age 9.7 yrs.) with ITP (41 acute, 49 chronic) were prospectively enrolled at six North American centers. Platelet count and bleeding severity were measured at baseline. Bleeding severity was assessed using a modification of a previously published grading instrument (J Pediatr , 141:683–8, 2002) where each patient was assigned a grade of 0 (no bleeding) to 5 (life-threatening bleeding) based on the overall amount of hemorrhage in the previous twenty-four hours. QoL scores were obtained by proxy-report by parents on behalf of their child and self-report by children age seven and older. Parents also reported their own QoL. Using a two- tailed Pearson correlation, the bleeding severity grade was weakly correlated with the platelet count in the children with chronic ITP (r= 0.20, p<0.001), but this relationship did not reach significance for children with acute ITP (r= 0.07, p= 0.09). The severity of bleeding did not correlate with the child's self-reported QoL in either acute (r= 0.005) or chronic ITP (r=0.03). Parents' self-assessed QoL did not reflect bleeding severity when their children had either acute (r= 0.03) or chronic ITP (r= 0.006). The parents' perception of the child's QoL using a proxy score was also poorly correlated with bleeding severity in acute (r= 0.02) and chronic ITP (r= 0.01). In summary, the bleeding severity score did not correlate with the QoL experienced by either the patient or the family in any setting. These results indicate that many factors in addition to bleeding signs may impact the children and parents, such as anxiety about the disease, length of hospital stay, frequency of visits to the physicians' office, and medication side effects. These findings suggest that the inclusion of multiple outcome measures enhances the scope of our knowledge and should be used in clinical care and research study design in order to understand the full spectrum of disease impact.

Initial management of children with newly diagnosed idiopathic thrombocytopenic purpura in the Nordic countries

To describe the management practices of newly diagnosed childhood idiopathic thrombocytopenic purpura (ITP) in the Nordic countries. A prospective registration was done from 1998 to 2000, including all children with newly diagnosed ITP aged 0-14 years and at least one platelet count < 30 x 10(9)/L. 506 children from 98 departments were registered. A diagnostic bone marrow aspiration was obtained within 14 days in 33%. Platelet and/or red blood cell transfusion was given in 11%. 287 children (57%) received platelet-enhancing therapy with intravenous immune globulin (IVIG) or corticosteroids within 14 days of diagnosis, IVIG being the first line choice in over 90% of the cases. There were noticeable national differences in the management. The decision to start drug treatment within two days of diagnosis was influenced mainly by the platelet count. Neither early treatment nor response to treatment changed the risk of chronic disease. This study has shown a great variation in the management practices of children with newly diagnosed ITP. Prospective studies are required to produce evidence-based recommendations for this patient group.

Initial management of children with newly diagnosed idiopathic thrombocytopenic purpura in the Nordic countries

Abstract Aim: To describe the management practices of newly diagnosed childhood idiopathic thrombocytopenic purpura (ITP) in the Nordic countries. Methods: A prospective registration was done from 1998 to 2000, including all children with newly diagnosed ITP aged 0–14 years and at least one platelet count &lt;30×109/L. Results: 506 children from 98 departments were registered. A diagnostic bone marrow aspiration was obtained within 14 days in 33%. Platelet and/or red blood cell transfusion was given in 11%. 287 children (57%) received platelet‐enhancing therapy with intravenous immune globulin (IVIG) or corticosteroids within 14 days of diagnosis, IVIG being the first line choice in over 90% of the cases. There were noticeable national differences in the management. The decision to start drug treatment within two days of diagnosis was influenced mainly by the platelet count. Neither early treatment nor response to treatment changed the risk of chronic disease. Conclusion: This study has shown a great variation in the management practices of children with newly diagnosed ITP. Prospective studies are required to produce evidence‐based recommendations for this patient group.

A cost‐utility analysis of treatment for acute childhood idiopathic thrombocytopenic purpura (ITP)

The primary objective in the treatment of acute pediatric idiopathic thrombocytopenic purpura (ITP) is to rapidly increase the platelet count. We built a decision analytic model to evaluate the cost-utility of four commonly used treatment strategies: intravenous immunoglobulin G (IVIG) 0.8 g/kg, anti-D 75 mcg/kg, methylprednisolone (30 mg/kg for 3 days), and prednisone (4 mg/kg/day for 4 days). In our baseline model, all children were hospitalized upon presentation, and discharged once the platelet count reached > or =20,000. We performed a literature search to estimate time to platelet count > or =20,000 for each strategy, as well as the probability of side effects. We obtained cost data and quality of life measures from institutional and published data sources. Total cost of one-time treatment for a 20 kg child was US dollars 786 with prednisone, US dollars 1,346 with methylprednisolone, US dollars 2,035 with anti-D, and US dollars 2,492 with IVIG. The strategies of IVIG and methylprednisolone were less effective and more expensive than anti-D and prednisone, respectively. Although anti-D caused the most rapid rise in platelet counts, the incremental cost-utility ratio (costs incurred by using anti-D instead of prednisone divided by health benefit of using anti-D instead of prednisone) was US dollars 7,616 per day of severe thrombocytopenia avoided, primarily due to the much higher medication cost of anti-D. Utilizing an outpatient model, the cost difference between anti-D and prednisone was even more striking. The clinical benefit of anti-D is offset by a substantial cost increase. Although often overlooked in favor of newer agents, a brief course of high-dose prednisone is an inexpensive and effective treatment for acute ITP.

Splenectomy for Chronic Idiopathic Thrombocytopenic Purpura in Children: A Single Center Study in China

The management of chronic and refractory idiopathic thrombocytopenic purpura (ITP) in children is controversial. We conducted a retrospective review of our single center experience in China between 1990 and 2003 with splenectomy for chronic ITP in children in order to determine the initial and long-term hematological response, morbidity, mortality, predictors of response to splenectomy and the therapy in children who failed splenectomy. Of 65 children analyzed, the overall immediate clinical response to splenectomy was 89.2%. The median postsplenectomy follow-up time was 52 months (8–124). During follow-up, 9 children (13.8%) relapsed within a median time of 6 months (2–58). The overall morbidity was 1.5% and perioperative mortality was zero. During follow-up, 1 child died of intracranial hemorrhage (ICH) and 1 died of overwhelming postsplenectomy infection (OPSI). The platelet count at day 7 after splenectomy was a predictor of a sustained response to splenectomy but no preoperative parameters were predictors of the response to splenectomy. Of the 15 children who failed splenectomy, excluding the one who died of ICH, only 2 children intermittently required corticosteroids and IVIG. Splenectomy is a potential therapy to provide long-term control of disease in children with chronic ITP and is associated with low morbidity and mortality. The risk of fulminant sepsis remains an omnipresent concern. Antipneumococcal vaccination and antibiotic prophylaxis should be recommended and children should receive timely and adequate antibiotics for bacteria infection to lessen the problem of OPSI.

Critical issues concerning splenectomy for chronic idiopathic thrombocytopenic purpura in childhood

Guidelines for management of chronic idiopathic thrombocytopenic purpura (ITP) in childhood are still based on expert opinions and therefore remain controversial. Splenectomy is an established option for chronic ITP in adults, but splenectomy in childhood is complex, due to higher probability for spontaneous recovery of ITP as compared to adults, psychological barrier of parents to accept a permanent organ loss, lack of reliable preoperative response prediction, and risk for overwhelming sepsis in young children. Parents are confronted with fear of intracranial bleeding, burden of responsibility in daily life, frequent visits to doctors, and need for restrictions of physical activities. Decision is further complicated by emerging conservative options offering durable remissions. This article reviews existing recommendations for splenectomy in pediatric chronic ITP and delineates critical and unsolved issues.

Idiopathic thrombocytopenic purpura (ITP) in children

Idiopathic thrombocytopenic purpura in children remits spontaneously in the majority of cases but most children require treatment. Between 1995 and 2005, 265 children (0-15 years old) have been consecutively observed and treated: 28 children with high doses of methylprednisolone (HDMP) (15 mg/kgx4 days), 63 with HDMP (7.5 mg/kgx4 days), 37 with HD dexamethasone (DXM) pulses, 29 with low doses of MP, and 51 with different doses of intravenous immunoglobulins (IVIG) (0.4 or 0.8 g/kg). Fifty-seven children have not been treated because of a platelet count>or=10x10(9)/L and no significant bleeding. Two hundred forty-four (92.1%) children reached a persistent CR, 237 (89.4%) after a first-line treatment or the wait and see strategy. No statistically significant differences in CR related to different treatments have been observed. IVIG and HDMP (7.5 mg/kg for 4 days) are the best treatments to reach quickly safe platelet levels>or=30x10(9)/L (3-6 days) and CR (7-11 days). Among non-responding (NR) patients, seven have been splenectomized and three reached stable CR. These results emphasize differences with adult ITP.

Idiopathic thrombocytopenic purpura in childhood: Controversies and solutions

Idiopathic thrombocytopenic purpura (ITP) is a bleeding disorder in patients who are otherwise healthy and present with thrombocytopenia with normal red cells and leukocytes. ITP is a diagnosis of exclusion and is in origin heterogeneous. The unknown etiology and the lack of clinical data from controlled prospective studies are reasons for controversies in diagnosis and management. Study endpoints traditionally include the velocity of platelet increase after drug intervention or observation, although a rapid elevation of the platelet count is of questionable clinical value. Evaluation of other endpoints is needed.

ITP in the 21st Century

Immune (or idiopathic) thrombocytopenic purpura (ITP) is commonly encountered by the practicing hematologist. Clinical management decisions have traditionally been guided by individual training and past experience. Input from the literature has been more from observational reports of case series than from scientific results of hypothesis-driven research. Practice guidelines and several surveys of clinical hematology practice have highlighted important questions in the field, and in the past 5 to 10 years both clinical and laboratory investigations have produced valuable new information. Thrombopoietin levels are normal or only slightly increased in ITP, and stimulation of thrombopoiesis appears to be a promising new therapeutic approach in clinical trials. Chronic, refractory ITP in children or adults remains a challenge for the hematologist. It is this group that has the greatest risk of serious bleeding, particularly among the elderly. The anti-B-cell monoclonal antibody, anti-CD20, has shown benefit in phase I/II clinical trials in patients who had failed a number of previous therapeutic modalities. The standard for clinical research into therapy for ITP has become evidence-based medicine, and more prospective, randomized clinical trials are being completed by multi-institutional study groups.

Idiopathic thrombocytopenic purpura: A 15-year natural history study at the Children's Hospital Rijeka, Croatia

We review a 15-year experience with childhood idiopathic thrombocytopenic purpura (ITP) at a tertiary-care pediatric hospital in Croatia. Data confirm that ITP is typically a self-limited bleeding disorder that usually presents with mild symptoms in children between 1 and 10 years of age and affects both sexes equally. At presentation, more than half of the children had platelet counts of <10x10(9)/L. The absence of preceding viral infection and insidious onset of symptoms were significantly associated with development of chronic ITP. In our experience, observation without specific therapy seems to be the optimal approach to a child with ITP.

Risk factors for future development of systemic lupus erythematosus in children with idiopathic thrombocytopenic purpura

The risk of later development of systemic lupus erythematosus (SLE) in childhood idiopathic thrombocytopenic purpura (ITP) is currently unknown. We retrospectively evaluated the incidence and risk factors of this complication in 222 children with ITP who were followed for a mean of 4.2+/-4.9 years. During that time 3.6% of the children (8/222) developed SLE; all were females with positive anti-nuclear antibody (ANA), older (12.7+/-3.6 vs. 6.4+/-4.3 years old; P<0.01), and were more likely to have chronic ITP (87.5 vs. 46%; P=0.02), and had high titers of ANA. The majority of children with ITP who had a positive ANA (14/22, 64%) did not develop SLE.

Consensus Guideline for Diagnosis and Treatment of Childhood Idiopathic Thrombocytopenic Purpura

A practice guideline aimed at standardizing the treatment for childhood idiopathic thrombocytopenic purpura (ITP) is presented. This consensus guideline is based on a survey carried out via a questionnaire prepared by the ITP Committee of the Japanese Society of Pediatric Hematology and sent to society members. The survey questionnaire included questions on the diagnosis of ITP submitted for the purpose of revising the ITP diagnostic guideline prepared in 1990 by the Research Group for Intractable Hematopoietic Disorders; a revised diagnostic guideline also is presented.

A review of anti-D treatment of childhood idiopathic thrombocytopenic purpura

Treatment of childhood idiopathic thrombocytopenic purpura is still an area of controversy. We reviewed the literature on anti-D treatment. Most studies used intravenous anti-D. Single doses of 50 microg/kg increased the platelet count to >or=20x10(9)/L in 70% of the children within 3 days. Intravenous anti-D seems safe in classic childhood ITP although hemolysis and occasionally renal failure may be of concern. A few studies reported intramuscularly or subcutaneously administered anti-D. Further studies on the optimal dose and route of administration of anti-D are warranted.

Current challenges in the management of children with idiopathic thrombocytopenic purpura

Much progress has been made during the past several decades in the diagnosis and management of childhood idiopathic thrombocytopenic purpura (ITP). Although we do not yet know ITP's cause, opportunities for research discovery in other areas have blossomed in recent years. One major step forward has been realization that outcomes other than platelet count are important in children with ITP, most especially the severity of hemorrhage, cost and side effects of treatment, and overall quality of life. The classical definition of chronic ITP (thrombocytopenia lasting greater than 6 months) has been questioned. Debate continues whether ITP can truly be cured, especially when it lasts for years. Much excitement has recently been generated as a result of a new mechanism of ITP treatment, that is, enhancing platelet production. Yet problems continue regarding how best to conduct research involving newly diagnosed ITP patients, for a number of barriers are still to be overcome. Fortunately, however, abundant information and support for ITP patients and their families is now much more available than in years past.

Subcutaneous Anti-D as Treatment of Idiopathic Thrombocytopenic Purpura in Children; Clinical Observations.

Treatment options for patients suffering from idiopathic thrombocytopenic purpura (ITP) mostly involve intravenous IgG (IVIG) or intravenous anti-D. Subcutaneous (s.c.) anti-D may be an attractive alternative; easy to administer and with less side effects. We present the clinical experience from treating six children suffering from ITP with s.c. anti-D.Five of the six patients had chronic ITP. One patient (patient number 3) had acute ITP. All patients with chronic ITP had been treated with IVIG prior to s.c. anti-D treatment, but not within four weeks before. Platelet counts (PLT) increased after all IVIG treatments, but for patient number 1 and 2 the increase was limited with repeated courses. Patient number 4 had also been treated with steroid with no effect.The number of anti-D treatments varied from 1–12. Only patient number 2 received 12 treatments. Doses were 50μg/kg or 75μg/kg anti-D. When treated, all patients had cutaneous bleeding. In patient number 1, episodes with epistaxis and gum bleeding also occurred.After s.c. anti-D cutaneous bleeding manifestations were reduced in five patients. In patient number 3 symptoms remained unchanged after the second treatment. Patient number 4 had no detectable clinical effect of the s.c anti-D.The effect on PLT varied greatly (table 1). Repeated increases in PLT to above 20•109/L were achieved in patient number 1. After the first treatment of patient number 2, PLT increased from 10•109/L to 37•109/L associated with a marked reduction in petechiae and bruising. In patient number 3 PLT increased only after the first treatment from 10•109/L to 67•109/L.Time till relapse also varied. Relapse is here defined as; the first day after treatment where PLT was continuously below 10*109/L for two weeks or more. For patient number 1 time till relapse after treatment increased. In patient number 2 bleeding tendency was reduced with regular treatments. Therefore, he was treated every four weeks for six months, and received, in total, 12 treatments over a 32 months period. Patient number 5 was treated twice. After the last treatment PLT has remained stable. Soreness and minor bruising at injection site were reported side effects.The average decrease in hemoglobin (Hgb) was 0.77 g/dL (range 0–2.4 g/dL). Lactate dehydrogenase (LDH) was not measured for all patients after every treatment, but the results available (table 1) indicated no or only minor degree of hemolysis. Patient number 3 reported dark morning urine 10 days after the second treatment. Dip-slide showed no hematuria. His Hgb was 11.0 g/dL and had decreased 0.5 g/ dL. LDH was not measured.Subcutaneous anti-D treatment was clinical effective with few side effects in five of six patients. Four of the five patients had been treated with IVIG prior to s.c. anti-D. Subcutaneous anti-D may be an attractive therapy, and the effect is under further investigation in a multi center trial.Demographic and paraclinical dataPatient numberSexAge at onset of ITP (Years)S.C. Anti-DDuration of ITP at treatment (months)PLT (start/end) [•109/L]Relapse (day after treatment)LDH (before →after) [U/I]1M3192–4 / 58–33456–125(no control)2M2176–16 / (no control)(no control)571→7323M1003- 10 / 7–6778*502→5234M4671 / 7n/a230→2275F497–19/ 67–93n/a240→2576F7103 / 6222292→321* After first treatment

Treatment of Acute Childhood Idiopathic Thrombocytopenic Purpura (ITP): A Cost-Utility Analysis.

Background & Aim: Controversy exists regarding treatment of children with typical acute ITP, a generally benign self-limited disease. Among physicians who actively treat ITP, the primary objective is to rapidly increase the platelet count to greater than 20x109/L. This practice is due to the belief that the greatest risk factor for intracranial hemorrhage (ICH) is the number of days of severe thrombocytopenia following the start of treatment. We built a decision analytic model to evaluate the cost-utility of four commonly used treatment strategies for acute ITP: 1) single dose 0.8 gm/kg IVIG 2) single dose 75 mcg/kg anti-D 3) methylprednisolone (IV) 30 mg/kg/dose given daily for 3 days or 4) oral prednisone 4 mg/kg/day given for 4 days with no tapering.Methods: In our model, we assumed that all children were hospitalized upon presentation, and were discharged once the platelet count reached ≥ 20x109/L. We also assumed that the incidence of ICH was 0.1%, regardless of treatment strategy. We performed a literature search to estimate the time to platelet count ≥ 20x109/L for each of the strategies, as well as the probability of side effects. We obtained quality of life measures (utilities) and cost data from institutional and published data sources. Costs included wholesale drug costs, infusion costs, hospitalization, and lost parental wages. Using a societal perspective, we compared strategies based on costs and quality-adjusted life-days (QALDs). Based on published data, and using declining exponential distributions, we estimated the average time to platelet count ≥ 20x109/L as follows: 1.4 days for IVIG, 0.7 days for anti-D, 2.4 days for methylprednisolone, and 1.6 days for prednisone.Results: The total cost of one-time treatment for a 20 kg child with acute ITP was $786 with prednisone, $1346 with methylprednisolone, $2035 with anti-D, and $2912 with IVIG. In the final analysis, the strategies of IVIG and methylprednisolone were dominated by prednisone. In cost-effectiveness analyses, a strategy is “dominated” when it is both less effective and more costly than an alternative strategy. Although anti-D caused the most rapid rise in platelet counts, the incremental cost-utility ratio (net increase in cost divided by net increase in health effect) of anti-D compared to prednisone was $7616 per QALD (day of severe thrombocytopenia avoided). Cost-utility results were sensitive to variation in hospitalization costs, anti-D costs, disutility of hospitalization, and estimated time to reach a platelet count ≥ 20x109/L.Conclusion: While the use of anti-D instead of prednisone leads to earlier hospital discharges in our model, this clinical benefit was offset by a substantial cost increase of $7616 per day of hospitalization and severe thrombocytopenia avoided. The higher total cost in the anti-D strategy was primarily due to the much higher medication cost of anti-D as compared to prednisone. Although often overlooked in favor of newer agents, a brief course of high-dose prednisone is an inexpensive and effective treatment for acute ITP.

Dapsone for chronic idiopathic thrombocytopenic purpura in children and adults – a report on 90 patients

Data on 90 patients (55 adults and 35 children) with chronic idiopathic thrombocytopenic purpura (ITP) and a platelet count of <50 x 10(9)/L treated with dapsone at a dose of 1-2 mg/kg/d are presented. A response was observed in 57 (63.3%) patients. The average time for response was 3.5 months (range 1-9) and the average duration of treatment with dapsone was 10.4 months (range 4-14). Overall response rates of 65.7% and 61.8% were observed in children and adults respectively. Side effects requiring discontinuation of therapy were observed in three (2%) patients. These results demonstrate that dapsone is an effective, inexpensive and well-tolerated treatment for chronic ITP, in both children and adults and could be considered for patients who fail steroid therapy.