Increasing observation rates in low‐risk pediatric immune thrombocytopenia using a standardized clinical assessment and management plan (SCAMP®)

An observational approach is recommended in newly diagnosed children with immune thrombocytopenia (ITP) at low risk of bleeding; however, there is no standard definition of risk. A standardized clinical assessment and management plan (SCAMP^®), a modifiable practice guideline, was implemented and revised (SCAMP‐1 and SCAMP‐2) and applied to 71 newly diagnosed patients with ITP. The Buchanan and Adix bleeding score guided treatment and was modified by stratifying by low‐ and high‐risk grade 3 bleeding in SCAMP‐2. Observation rates increased from 40% to 74% from SCAMP‐1 to SCAMP‐2 (P < 0.05) with no bleeding complications. We propose a modified bleeding score that increased observation rates in low‐risk patients with ITP.     

Local and cultural aspects of childhood idiopathic thrombocytopenic purpura: a summary of statements from the 12 countries worldwide

Idiopathic thrombocytopenic purpura (ITP) is a heterogeneous bleeding disorder. The Intercontinental Childhood ITP Study Group (ICIS) analyzed demographic data and outcome in a prospective registry of over 2,000 children with ITP. In addition, participating centers from 12 different countries worldwide were asked to describe their local and cultural aspects of ITP management to provide a summary statement of the variable diagnostic and management approaches for childhood ITP. The statements of the 15 reports from 12 countries are summarized under eight main areas to reflect the variability in approach to ITP among different countries. The management of ITP in children differs dramatically worldwide in terms of observation only, medical treatment, bleeding symptoms, acceptable platelet counts, need for hospitalization or outpatient treatment, and medical care climate. The majority of experimental treatments, surveys, and guidelines are not evidence-based. Although there is a great need for cooperative studies to learn more about diagnosis, management, and prognosis in the heterogeneous disorder of ITP, local and cultural variations must be considered in international investigations.     

Ethnicity and environment may affect the phenotype of immune thrombocytopenic purpura in children

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.     

Investigation and management of newly diagnosed childhood idiopathic thrombocytopenic purpura: problems and proposed solutions

The purpose of this paper is to describe current problems in investigation and management of newly diagnosed childhood idiopathic thrombocytopenic purpura (ITP). An Intercontinental Childhood ITP Study Group was established in 1997 with the aim to promote international clinical research based on a research environment and network of physicians. Initial and still ongoing projects include registries to collect data on the natural history of ITP, demographics of patients with ITP, and its management. Registry I was successful, with data on almost 3,000 patients from 38 countries. Registry II investigates the occurrence and severity of bleeding at the time of diagnosis and within 2 years of follow-up. Current problems are listed and discussed. An international network of physicians similar to that of malignant diseases for the conduct of clinical research and regular scientific meetings is the basis for solutions of the identified problems.     

Idiopathic thrombocytopenic purpura: beyond consensus

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.     

Duration and morbidity of newly diagnosed idiopathic thrombocytopenic purpura in children: A prospective Nordic study of an unselected cohort

OBJECTIVE: 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). STUDY DESIGN: 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. RESULTS: 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. CONCLUSION: 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.     

NK细胞在儿童免疫性血小板减少症发病和治疗中的意义

目的：探讨自然杀伤细胞（NK细胞）在儿童免疫性血小板减少症（ITP）的发病和治疗中的意义。方法采用流式细胞仪分别检测62例新诊断ITP患儿、43例持续性ITP患儿、21例慢性ITP患儿和51例对照组儿童外周血NK细胞百分比;并观察单独使用标准剂量静脉注射用人免疫球蛋白（IVIG）对NK细胞百分比正常及减少的新诊断的ITP患儿的疗效。结果新诊断ITP患儿、持续性ITP、慢性ITP患儿NK细胞百分比均较正常对照组儿童显著降低（P＜0.05）,但三组ITP患儿NK细胞百分比差异无显著性（P ！0．05）;NK细胞百分比正常的新诊断ITP患儿单独使用IVIG有效率为92．86％（26/28）,NK细胞百分比降低的新诊断ITP患儿单独使用IVIG有效率仅为14．70％（5/34）。结论 NK细胞表达变化与ITP发病存在一定关系,同时NK细胞百分比正常的新诊断ITP患儿可首选IVIG治疗。     

Evaluation of Japanese practice guidelines for newly diagnosed childhood idiopathic thrombocytopenic purpura

Background: Practice guidelines for childhood idiopathic thrombocytopenic purpura (ITP) were proposed in 1998 and 2004 in Japan. It is important to evaluate the feasibility and validity of the guidelines because the guidelines are based not on evidence but on opinion. Methods: Records of 30 consecutive hospitalized patients aged 0–15 years (median, 3 years; 17 boys, 13 girls) were retrospectively reviewed. The feasibility and validity of the 2004 guidelines were evaluated by calculating an implementation rate, a response rate to first treatments, and a final clinical outcome. Results: Deviation from the guidelines was found in two patients. Management of the other 28 patients followed the guidelines. The implementation rate was 93.3%. Twenty‐one of the 28 eligible patients (75%) responded to the first treatment, whereas seven patients (25%) required additional treatment. In 23 patients (76.7%) platelet counts returned to normal within 6 months. Seven patients (23.3%) developed chronic conditions. All patients had no complications and achieved a platelet count >150 000/µL within 6 years. Conclusion: The 2004 Japanese guidelines are feasible and valid for the management of newly diagnosed childhood ITP patients.     

Efficacy and safety of anti-D for immune thrombocytopenic purpura in children

This study was conducted in 20 children (16 males) (mean age 9.2 ± 4.34y) with immune thrombocytopenic purpura (ITP) to assess the response to anti-D immunoglobulin. Six patients had newly diagnosed ITP, 6 had persistent ITP and 8 had chronic ITP. The overall response rate was 70% (14/20). The median time to response was 3 days (1–13 days). Response to anti-D was not related to age, sex, severity of bleeding, platelet counts at presentation, ABO blood group, or prior steroid or IVIG response.     

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

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 < 30 x 10(9)/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.     

血小板相关抗体与儿童特发性血小板减少性紫癜转归的相关性分析

目的探讨血小板相关抗体(PAIg)与儿童特发性血小板减少性紫癜(ITP)转归的相关性。方法选择2008年12月-2010年12月江西省儿童医院收治的急性ITP患儿200例,应用ELISA方法检测患儿初诊时及治疗前后PAIg的表达,并与临床疗效相比较。结果 ITP患儿初诊时PAIgG、PAIgA及PAIgM抗体表达水平高于正常对照组;PAIgG、PAIgM、PAIgA表达水平与血小板计数之间均呈负相关。难治组ITP患儿初诊时PAIgM抗体水平要明显高于激素治疗有效的急性ITP患儿,并且PAIgM异常增高或合并PAIgG增高的比例显著高于急性ITP患儿(P<0.05)。治疗后,PAIgG和PAIgM同时升高的ITP患儿,治愈和显效组两种抗体水平均有显著下降(P<0.05),难治组两种抗体水平下降不明显(P>0.05)。结论 ITP的发生与血小板抗体水平增高密切相关,初诊ITP患儿PAIgM单独或合并PAIgG异常增高常提示预后不良。     

Childhood idiopathic thrombocytopenic purpura in the Nordic countries: epidemiology and predictors of chronic disease

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 x 10(9)/l. RESULTS: 506 children were registered and 423 followed for 6 mo. The incidence was 4.8/10(5) 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 x 10(9)/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.     

Prednisone therapy for children with newly diagnosed idiopathic thrombocytopenic purpura. A randomized clinical trial

The efficacy of corticosteroids in childhood acute idiopathic thrombocytopenic purpura (ITP) is controversial and has infrequently been evaluated in a controlled randomized fashion. We administered prednisone (2 mg/kg/day for 14 days with subsequent tapering and discontinuation by day 21) or placebo to 27 children, aged 10 years or less, with newly diagnosed ITP. Platelet count, bleeding time (a test of the integrity of the platelet-microvasculature interaction), and clinical bleeding score (based on a 0-4 scale) were determined before (day 0) and six times following initiation of drug therapy (days 1-2, 3-5, 7, 14, 21, and 28). There were no statistically significant (p less than 0.05) differences between the two treatment groups in any of the three study parameters except on day 7 of therapy when children receiving prednisone had higher platelet counts and lower bleeding scores and bleeding times than those taking placebo. Bleeding time correlated inversely with the platelet count in both treatment groups. Prednisone did not appear to influence bleeding time independent of its effect on platelet count. This treatment regimen of prednisone did not clearly improve hemostasis in childhood acute ITP except transiently at the end of 1 week of treatment.     

Childhood ITP: 12 months follow-up data from the prospective registry I of the Intercontinental Childhood ITP Study Group (ICIS)

BACKGROUND: Acute and chronic idiopathic thrombocytopenic purpura (ITP) is traditionally based on the duration of thrombocytopenia at the cut-off point of 6 months after diagnosis. Registry I evaluated the diagnosis, definition, management, and follow-up of childhood ITP. This report focuses on children with thrombocytopenia persisting more than 6 months. PROCEDURE: Data were collected by questionnaires to the physicians caring for children with ITP, at diagnosis, 6, and 12 months later. Data were compared regarding initial features and follow-up with emphasis on children with persistent thrombocytopenia, and those with ITP who recovered their platelet counts between 7 and 12 months from diagnosis. RESULTS: At 12 months from diagnosis, 79 of 308 (25.6%) evaluable children recovered from ITP and 229 had ongoing ITP. Children with recovered ITP were younger than children with ongoing ITP (P = 0.043) and exhibited a lower frequency of bleeding symptoms during the first 6 months after diagnosis (P = 0.018). Frequency of hospitalization, bone marrow aspiration, and drug treatment differed regionally. CONCLUSIONS: The high rate of recovery from ITP between 7 to 12 months demonstrates, that the cut-off point of 6 months for the definition of chronic ITP does not adequately differentiate chronic from acute ITP. The majority of children with ITP have variable time to recovery with gradual improvement of platelet counts and disappearance of bleeding signs. ITP is a heterogeneous disorder with a diverse natural history and diverse pattern of treatment response.     

儿童免疫性血小板减少症树突状细胞与T淋巴细胞分化失衡的关系

目的探讨树突状细胞和T淋巴细胞分化失衡与儿童免疫性血小板减少症(ITP)的关系及临床意义。方法用流式细胞术分别检测ITP患儿和对照者外周血Th细胞、Ts细胞、Treg细胞及树突状细胞变化。结果在持续性和慢性ITP组中Th细胞、Treg细胞和Th/Ts细胞比值降低,而Ts细胞升高,与对照组相比差异有显著性(P<0.05),与新诊断ITP组相比差异亦有显著性(P<0.05);Treg细胞在新诊断ITP组降低,与对照组比较差异有显著性(P<0.05);在慢性ITP组中浆细胞样树突状细胞(pDC)绝对值降低,髓样树突状细胞(mDC)/pDC比值增高,与对照组和新诊断ITP组比较差异有显著性(P<0.05)。60例ITP患儿经过糖皮质激素治疗后有39例完全缓解,12例部分缓解,9例无效。在无效组中Th细胞降低,而Tc细胞增高,与对照组和完全缓解组比较差异有显著性(P<0.05);Treg细胞和pDC绝对值在无效组和部分缓解组中降低,与对照组比较差异有显著性(P<0.05),无效组与完全缓解组比较差异亦有显著性(P<0.05)。结论 T淋巴细胞亚群和DC亚群比例失衡与儿童持续性和慢性ITP的发病及儿童ITP的临床分期和预后有关。     

Self-reported initial management of childhood idiopathic thrombocytopenic purpura: results of a survey of members of the American Society of Pediatric Hematology/Oncology, 2001

The purpose of this study was to update physicians' self-reported initial management practices for childhood idiopathic thrombocytopenic purpura (ITP) from an initial survey in 1997. A questionnaire was sent by e-mail in October 2001 to 753 members of the American Society of Pediatric Hematology/Oncology (ASPH/O). The questionnaire had 14 questions, based on the clinical presentation of a 5-year-old boy with ITP, a platelet count of 7,000/microL, scattered petechiae, and no mucous membrane bleeding. Two hundred eighteen (29%) surveys were returned. In response to questions regarding initial treatment, 33% of physicians said they would always administer drug therapy, 38% usually, 15% sometimes, and 14% rarely/never. When asked which agent would be used if drug treatment were prescribed, 45% reported anti-D, 33% IVIG, 20% prednisone, and 2% other regimens. Only 34% of physicians would always or usually hospitalize such a patient. Hospitalization was more likely if a physician responded that he or she would always or usually use drug therapy. Physicians who saw more ITP patients were more likely to self-report sometimes or rarely/never prescribing drug therapy. Self-reported initial management of ITP by ASPH/O members in 2001 is similar to 1997 regarding the percentage of pediatric hematologists who would not use drug therapy. Among physicians who would use drug treatment, there was an increased use of anti-D and decreased use of IVIG and prednisone. This information provides the basis for designing a randomized clinical trial to compare the effect of different management strategies on the outcomes of bleeding symptoms, side effects of therapy, costs, and quality of life.     

Idiopathic thrombocytopenic purpura in adults

Immune thrombocytopenic purpura (ITP) is an organ-specific autoimmune disorder in which platelets opsonized by antiplatelet antibodies are destroyed by the reticuloendothelial system. As a result the peripheral blood platelet count is low; if sufficiently severe, it may lead to bruising and mucocutaneous bleeding. The disorder may occur in adults and in children; in the former the disease affects primarily females, whereas the childhood type affects the sexes equally. For most individuals the disorder is minor, requiring little treatment, but patients with more severe forms of the disease require therapy to elevate the platelet count to a safe level to prevent serious bleeding. Therapies include corticosteroids, intravenous immunoglobulin, splenectomy, and immunosuppressive agents. Because there have been few trials in ITP, there is little evidence to guide treatment, and all the treatments may have adverse effects in terms of morbidity and mortality. The American Society of Hematology and British Committee for Standards in Haematology guidelines provide a framework for management but nonetheless are based on little evidence. In this paper the authors review the management of ITP in adults, children, and pregnant women and highlight some of the novel therapies being explored in this disorder, in addition to some of the ongoing laboratory research exploring the mechanisms underlying the disease.     

Peritoneal hemorrhage due to a ruptured ovarian cyst in ITP

Immune thrombocytopenic purpura in children rarely causes severe bleeding. The incidence of intracranial hemorrhage is approximately 0.2% to 1.0%, and severe bleeding (defined as persistent epistaxis, melena, menorrhagia, gastrointestinal bleeding, etc, requiring hospitalization or transfusion) occurs in only 5% of patients. Epstein-Barr virus (EBV) associated idiopathic thrombocytopenic purpura (ITP) tends to behave similarly to non-EBV - associated ITP with no increase in hemorrhagic complications and only a small increase in time to remission. Immune thrombocytopenic purpura diagnosed in adolescence is more likely to be chronic then in childhood ITP, but has a higher rate of spontaneous resolution than in adults. However, females in this age group are in their early childbearing years and present a unique set of possible hemorrhagic complications not seen in younger patients. We present the case of an 18-year-old female with EBV-associated ITP, who developed a severe intra-abdominal bleed secondary to a hemorrhagic ovarian cyst.     

Idiopathic thrombocytopenic purpura diagnosed during the second decade of life

OBJECTIVE: To retrospectively review our institutional experience of adolescents with idiopathic thrombocytopenic purpura (ITP). STUDY DESIGN: 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. RESULTS: 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. CONCLUSIONS: 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.