Utilization of an ITP quality improvement pathway improves adherence to management guidelines

Despite availability of epidemiologic studies and national guidelines for the management of newly diagnosed pediatric immune thrombocytopenia (ITP), practice variation exists among and within hematology practices. We previously described the development of an ITP pathway guiding management based on bleeding symptoms. Over an 8-year period, integration of this iterative ITP pathway into management of newly diagnosed ITP increased observation rates in children with no or mild bleeding symptoms and improved consistency of laboratory evaluation and treatment strategies without increasing adverse outcomes. This quality improvement initiative has been sustainable, acceptable to providers, and increased adherence to guidelines.     

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。     

Use of Romiplostim for Primary Immune Thrombocytopenia in Children

Very little has been published on the use of romiplostim to treat primary immune thrombocytopenia (ITP), refractory to previous treatments, in children. The objective of this study was to determine its efficacy and safety in pediatric patients in a university general hospital. Retrospective, longitudinal observational study of pediatric patients on treatment with romiplostim. The principal efficacy variable was platelet count. Safety was evaluated by recording possible adverse reactions to the medication, monitoring the appearance of thrombosis, thrombocytopenia during dose reduction, hemorrhage, and myelodysplastic syndromes. Three patients in the authors’ center have been treated with romiplostim (subcutaneous [SC], initial dose: 1 μg/kg/week) for ITP refractory to various treatments: 1 with newly diagnosed ITP and 2 with chronic ITP. Patients were followed up for 27 to 39 weeks after starting treatment. Responses were achieved in 7 to 28 days, and complete responses were maintained for 37% to 91% of the follow-up period, with median platelet counts between 40 × 10³/μL and 215 × 10³/μL. The adverse reactions observed during follow-up were headache and asthenia in one patient and mucocutaneous bleeding after dose suspension in another one. With regard to effectiveness, the response in the 3 patients was varied. The drug was considered to be safe, as there were only mild adverse reactions. Although further studies and long-term follow-up are required, these results show that romiplostim could be considered an alternative to immunosuppressive therapies, such as rituximab, or splenectomy in refractory chronic ITP.     

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.     

Use of romiplostim for primary immune thrombocytopenia in children

Very little has been published on the use of romiplostim to treat primary immune thrombocytopenia (ITP), refractory to previous treatments, in children. The objective of this study was to determine its efficacy and safety in pediatric patients in a university general hospital. Retrospective, longitudinal observational study of pediatric patients on treatment with romiplostim. The principal efficacy variable was platelet count. Safety was evaluated by recording possible adverse reactions to the medication, monitoring the appearance of thrombosis, thrombocytopenia during dose reduction, hemorrhage, and myelodysplastic syndromes. Three patients in the authors' center have been treated with romiplostim (subcutaneous [SC], initial dose: 1 μg/kg/week) for ITP refractory to various treatments: 1 with newly diagnosed ITP and 2 with chronic ITP. Patients were followed up for 27 to 39 weeks after starting treatment. Responses were achieved in 7 to 28 days, and complete responses were maintained for 37% to 91% of the follow-up period, with median platelet counts between 40 × 10(3)/μL and 215 × 10(3)/μL. The adverse reactions observed during follow-up were headache and asthenia in one patient and mucocutaneous bleeding after dose suspension in another one. With regard to effectiveness, the response in the 3 patients was varied. The drug was considered to be safe, as there were only mild adverse reactions. Although further studies and long-term follow-up are required, these results show that romiplostim could be considered an alternative to immunosuppressive therapies, such as rituximab, or splenectomy in refractory chronic ITP.     

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.     

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。     

Thrombocytopenic syndromes masquerading as childhood immune thrombocytopenic purpura

Immune thrombocytopenic purpura (ITP) is the most common cause of thrombocytopenia in children and adolescents. However, there are a number of other diagnoses that are often mistaken for ITP. A 10-year retrospective chart review was performed at the Children's Hospital of Alabama to characterize ITP. Initially, 492 patients who had the coded diagnosis of ITP (ICD 287.3) were identified. However, 83 (17%) of patients were found to have alternative diagnoses on chart review. Of the 83 patients, 13 patients (3%) represented coding errors or study classification errors. The 70 remaining patients (14%) had an alternative explanation for their thrombocytopenia, consisting of 31 different diagnoses. The most common diagnoses were familial thrombocytopenia (10%), systemic lupus erythematosus (9%), hypersplenism (9%), neonatal alloimmune thrombocytopenia (7%), Wiskott-Aldrich syndrome (7%), or systemic infection (6%). In total, 16 of the patients (23%) were ultimately diagnosed with one of a number of congenital syndromes with concurrent thrombocytopenia. Although this review confirms that most children with thrombocytopenia are diagnosed with ITP, 14% of the study population manifested other diagnoses. The clinician evaluating a child with thrombocytopenia must keep an open mind about the possible diagnosis and perform a comprehensive and thoughtful evaluation based on the clinical picture. ITP must be a diagnosis of exclusion as misdiagnosis in a child with thrombocytopenia may have a significant impact on morbidity and mortality.     

Serum leptin levels in patients with childhood immune thrombocytopenic purpura

Acute immune thrombocytopenic purpura (ITP) induces thrombocytopenia by means of an autoimmune mechanism. Recent studies suggested that T helper immune response is responsible for the pathogenesis of chronic ITP. Despite several studies that were carried out, we do not have a clue as to what triggers the autoimmunity. Leptin is a 16-kd protein secreted from the adipose tissue. Leptin is structurally similar to interleukin (IL)-2, IL-6, and IL-15. The structural similarities between leptin receptor and hematopoietic cytokine receptors suggested that leptin could play a role in hematopoiesis and immune function. Recent studies suggested that leptin could play an important role in autoimmunity. We made a prospective analysis of a series of 39 newly diagnosed acute childhood ITP in a year period. Serum leptin levels were obtained after diagnosis and before treatment and all patients were followed up at least 6 months to designate acute or chronic event. We conclude that in childhood acute ITP, leptin did not play a role in the pathophysiology of the disease. Further investigations are needed to examine what triggers T cells and how the autoimmune disease became.     

Role of parvovirus B19 infection in childhood idiopathic thrombocytopenic purpura

Although parvovirus B19 exhibits a strong tissue-tropism for erythroid progenitor cells leading to anaemia, several case reports indicate that parvovirus B19 infection may also cause the development of thrombocytopenia. Despite recent studies, the frequency and clinical relevance of this association have remained questionable. Consequently, and in view of the paucity of evidence regarding a viral aetiology for idiopathic thrombocytopenic purpura (ITP), we examined the role of parvovirus B19 in 47 children with newly diagnosed ITP. Specific viral DNA indicating a current or recent parvovirus B19 infection was demonstrated in 6 of 47 patients (13%) employing the polymerase chain reaction technique. Our study suggests that children with ITP and associated parvovirus B19 infection are characterized by acute onset of profound thrombocytopenia. Among the parvovirus B19 positive children, duration of disease was brief in three children treated with immunoglobulin but chronic in the remaining three patients given high-dose steroids. Prospective studies are needed to confirm these initial observations. This virus should be considered as a possible aetiologic agent in some children with ITP.     

The effect of anti-thyroid antibodies positivity on children with primary immune thrombocytopenia

Primary immune thrombocytopenia (ITP) is the most common cause of acquired thrombocytopenia in children. Anti-thyroid antibodies (aTA) have previously been found to be present in various autoimmune diseases. Our aim was to study the effect of aTA positivity (which are anti-thyroid peroxidase (aTPo) and/or anti-thyroglobulin (aTg)) on children with primary immune thrombocytopenia and their relation to treatment response. Sixty-one children with primary ITP were enrolled in the present study. They were further subdivided into: ND&P group (newly diagnosed and persistent) and chronic ITP group. Seventy-five apparently healthy children were enrolled as control group. aTPo and aTg antibodies were significantly higher and more frequently positive in all children with ITP and in each ITP group than the control group (P <.05 in all). But, there were no statistically significant differences between the two ITP subgroups (P >.05). aTA positive children with ITP had significantly lower platelet count: at the start of treatment (P =.009), after receiving methylprednisolone or intravenous immunoglobulin (P =.02) and at one month follow-up (P =.003) than aTA negative children with ITP. Lastly, aTA positive children had more relapses (P =.03), continued more frequently to have relapses after one year in the ND&P group (P =.02) and required immunosuppressive therapy more frequently in the chronic ITP group (P =.005).     

甲状腺球蛋白抗体和甲状腺过氧化物酶抗体在儿童免疫性血小板减少症中的表达及临床意义北大核心CSCD

目的观察免疫性血小板减少症(immune thrombocytopenia,ITP)患儿血清甲状腺球蛋白抗体(thyroglobulin antibody,TGAb)、甲状腺过氧化物酶抗体(thyroid peroxidaseantibody,TPOAb)的表达情况。方法前瞻性选择2019年10月至2021年10月收治的120例ITP患儿作为ITP组,另选择60例非ITP患儿作为非ITP组。根据ITP临床分型将ITP组患儿分为新诊断ITP(n=53)、持续性ITP(n=42)与慢性ITP(n=25)。比较ITP组与非ITP组、不同ITP临床分型患儿临床资料,分析ITP患儿血清TGAb、TPOAb表达情况,及其与ITP临床分型的关系。结果ITP组CD_(3)^(+)、CD_(4)^(+)比例及血小板计数低于非ITP组,CD_(8)^(+)比例及TGAb、TPOAb水平高于非ITP组(P<0.05);慢性ITP患儿CD_(3)^(+)、CD_(4)^(+)比例及血小板计数低于新诊断ITP、持续性ITP患儿,CD_(8)^(+)比例及TGAb、TPOAb高于新诊断ITP、持续性ITP患儿(P<0.05)。经logistic回归分析结果显示,CD_(3)^(+)、CD_(4)^(+)、CD_(8)^(+)、TGAb、TPOAb表达水平变化与慢性ITP的发生密切相关(P<0.05);绘制决策曲线,结果显示,在高风险阈值0.0~1.0范围内TGAb联合TPOAb评估儿童ITP临床分型的净收益率始终>0,有临床意义。结论TGAb、TPOAb在ITP患儿中呈异常表达,且与患儿ITP临床分型有关。     

《2019年美国血液学会免疫性血小板减少症指南》儿童部分解读

免疫性血小板减少症（immune thrombocytopenia,ITP）是一种获得性自身免疫性疾病,其主要机制为血小板破坏过多及生成受阻导致血小板计数减少。一般人群中ITP的发病率为2/10万～5/10万。新版指南提供了儿童ITP一线和二线治疗方案,一线治疗方案包括观察、门诊、皮质类固醇、抗D免疫球蛋白、静脉注射免疫球蛋白（intravenous immunoglobulin,IVIG）,二线治疗方案包括利妥昔单抗、血小板生成素受体激动剂（thrombopoietin receptor agonists,TPO-RA）、脾切除术。另有一些三线药物治疗但指南未给出明确建议。     

2019年《原发性免疫性血小板减少症的调查和管理：国际共识报告更新》儿童部分解读

近十年来,原发性免疫性血小板减少症（ITP）的诊治和管理进展突飞猛进。基于新证据的不断涌现,2019年新的ITP国际工作组对2010版国际共识报告（ICR）做了更新。新共识针对成人、妊娠期和儿童ITP的诊治管理进行了全面详尽的指导,包括诊断与鉴别诊断、一线治疗、危急重症抢救治疗、二线治疗、生活质量管理及体育活动建议等。该文就共识中儿童ITP相关内容进行重点解读,为临床规范化诊治提供依据。     

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.     

Prednisone treatment of acute idiopathic thrombocytopenic purpura of childhood. Advantages

Idiopathic thrombocytopenic purpura (ITP), an acquired hemorrhagic disorder, is characterized by the abrupt onset of thrombocytopenia despite normal megakaryocytic productivity. An accumulating body of evidence, including the recent demonstration of elevated levels of platelet-associated IgG, points to an immune etiology of acute childhood ITP. Although spontaneous recovery occurs in 80-90% of patients within 4 months of diagnosis, hemorrhagic complications may occur. Considerable evidence exists which suggests the efficacy of corticosteroid use in this disorder. Several clinical studies have shown that steroids may shorten the time to platelet count recovery, thus reducing the time at risk for hemorrhagic complications. The authors conclude with treatment recommendations for childhood ITP which include a brief course of prednisone.     

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.     

儿童新诊断免疫性血小板减少症与幽门螺杆菌感染的相关性研究

目的明确幽门螺杆菌(H.pylori)感染对儿童新诊断免疫性血小板减少症(ITP)的影响。方法选取2011年1月至2013年12月间首次住院并新诊断为ITP的495例患儿为病例组;随机选取无血小板减少及其他血液系统疾病的普通呼吸道感染住院患儿123例作为对照组。依据年龄将两组患儿分为1岁组(n=219)、1岁~组(n=161)、3岁~组(n=76)和7~14岁组(n=39)。回顾性分析各年龄段患儿H.pylori感染率,以及H.pylori感染阳性及阴性ITP患儿经过相同治疗后的预后情况。结果病例组中H.pylori感染率随着ITP患儿年龄的增长而增加,与对照组各年龄段H.pylori感染率比较差异均无统计学意义(均P0.05)。H.pylori感染阳性ITP患儿均未接受针对H.pylori的相关治疗,而针对血小板减少经丙种球蛋白和/或激素治疗后缓解率随着年龄的增长而呈现逐渐下降趋势,与各年龄段H.pylori阴性的ITP患儿治疗后缓解率比较差异均无统计学意义(均P0.05)。结论 H.pylori感染可能不是ITP患儿发病的一个主要致病因素;是否治疗H.pylori并不影响儿童急性ITP的治疗效果。     

Immune Thrombocytopenia in Children: Consensus and Controversies

Indian Journal of Pediatrics - Newly diagnosed immune thrombocytopenia (ITP) is a relatively common disorder of childhood that does not require an exhaustive laboratory workup for diagnosis. A...     

Clinical practice: immune thrombocytopenia in paediatrics

Immune thrombocytopenia (ITP) is a disease affecting both children and adults. It is defined as acquired isolated thrombocytopenia caused by the autoimmune production of anti-platelet antibodies. Childhood ITP most frequently occurs in young children who have been previously well, although a viral respiratory tract infection often precedes thrombocytopenia. A benign and self-limiting course is common, but major bleeding complications such as intracranial haemorrhage may occur. Yet one cannot predict which child will have a prolonged course of thrombocytopenia and who will develop an intracranial haemorrhage. In children without atypical characteristics, only minimal diagnostic investigations are needed, and most paediatric ITP patients do not need platelet-enhancing therapy even though various treatment options are available. A “watch and wait” strategy should be considered in paediatric patients with mild disease. Steroids, intravenous immunoglobulin G or anti-D immunoglobulin are the current first-line therapeutic measures for children at risk for severe bleeding. When life-threatening bleeding occurs, a combination of therapies is needed. In this review, we summarise the current knowledge on primary ITP in children and adolescents.