Pulsed high-dose dexamethasone therapy in children with chronic idiopathic thrombocytopenic purpura

The effectiveness of pulsed high-dose oral dexamethasone therapy in children with refractory chronic idiopathic thrombocytopenic purpura (ITP) is evaluated. Thirteen children with severe chronic ITP were enrolled in the study from an outpatient pediatric hematology clinic (ages 2-14 years), 5 boys and 7 girls. They did not maintain a response to other forms of therapy (IVIg, Anti-D, conventional steroids, danazol) and one girl relapsed after splenectomy. Dexamethasone was administered orally at a dosage of 40 mg/M2/day (maximum 40 mg/day) for 4 consecutive days. The cycle was repeated once a month for 6 months. The immediate response to therapy was excellent as the mean platelet count at day 1 was 15 x 10(9)/L, while mean platelet count at day 4 was 158 x 10(9)/L. At the end of 6 cycles 3 patients maintained a platelet count of >150 x 10(9)/L and 4 patients showed partial response. At the end of the first year and second year (12 and 24 months after onset of treatment) 3 patients still had complete response, 3 patients had partial response, and 7 patients were failures. Six of the failures underwent splenectomy and one was shifted to dapsone, had no response, and refused splenectomy. Side effects were tolerable. They included bloating, nausea, vomiting, insomnia, anxiety, and depression, and transient glucosuria; however, they were not severe enough to discontinue the cycles. Mean duration of illness prior to start of dexamethasone was not significantly different in between responders and nonresponders. Dexamethasone given orally in high doses is an effective drug in achieving short-term platelet responses. Long-term remission is obtained in nearly half the patients with well-established chronic ITP. Its effectiveness in almost half the patients, minimal side effects, and low cost indicate that this treatment should be considered in patients with chronic ITP who do not tolerate the disease well before considering splenectomy.     

PULSED HIGH-DOSE DEXAMETHASONE THERAPY IN CHILDREN WITH CHRONIC IDIOPATHIC THROMBOCYTOPENIC PURPURA

The effectiveness of pulsed high-dose oral dexamethasone therapy in children with refractory chronic idiopathic thrombocytopenic purpura (ITP) is evaluated. Thirteen children with severe chronic ITP were enrolled in the study from an outpatient pediatric hematology clinic (ages 2-14 years), 5 boys and 7 girls. They did not maintain a response to other forms of therapy (IVIg, Anti-D, conventional steroids, danazol) and one girl relapsed after splenectomy. Dexamethasone was administered orally at a dosage of 40 mg/M2/day (maximum 40 mg/day) for 4 consecutive days. The cycle was repeated once a month for 6 months. The immediate response to therapy was excellent as the mean platelet count at day 1 was 15 &#50 10 9 /L, while mean platelet count at day 4 was 158 &#50 10 9 /L. At the end of 6 cycles 3 patients maintained a platelet count of >150 &#50 10 9 /L and 4 patients showed partial response. At the end of the first year and second year (12 and 24 months after onset of treatment) 3 patients still had complete response, 3 patients had partial response, and 7 patients were failures. Six of the failures underwent splenectomy and one was shifted to dapsone, had no response, and refused splenectomy. Side effects were tolerable. They included bloating, nausea, vomiting, insomnia, anxiety, and depression, and transient glucosuria; however, they were not severe enough to discontinue the cycles. Mean duration of illness prior to start of dexamethasone was not significantly different in between responders and nonresponders. Dexamethasone given orally in high doses is an effective drug in achieving short-term platelet responses. Long-term remission is obtained in nearly half the patients with well-established chronic ITP. Its effectiveness in almost half the patients, minimal side effects, and low cost indicate that this treatment should be considered in patients with chronic ITP who do not tolerate the disease well before considering splenectomy.     

在慢性免疫性血小板减少症患儿中甄别原发性免疫缺陷症

原发性免疫缺陷症(primary immunodeficiency,PID)是一组由免疫通路上特定功能性位点突变引起免疫调控异常的遗传性疾病,免疫性血小板减少为其常见表现,且病程迁延、反复,呈现慢性免疫性血小板减少状态.而免疫性血小板减少症(immune thrombocytopenic purpura,1TP)是儿童...     

Soluble P-selectin,interleukin 6, and thrombopoietin levels in children with acute and chronic idiopathic thrombocytopenic purpura and their relationship with mega-dose methylprednisolone therapy: a pilot study

We observed less severe symptoms in patients with chronic idiopathic thrombocytopenic purpura (ITP) than in patients with acute ITP with similar platelet counts. Thrombopoietin (TPO), soluble P-selectin, soluble P-selectin per platelet, and interleukin 6 (IL-6) were evaluated in children with ITP before treatment in 16 acute and 22 chronic cases and after treatment in 10 acute and chronic cases who received mega-dose methylprednisolone. The levels of IL-6, soluble P-selectin, soluble P-selectin per platelet, and platelet count were similar in acute and chronic ITP (P > 0.05) but TPO in acute ITP was higher than that of the patients with chronic ITP (P < 0.05). The posttreatment IL-6 and TPO declined (P < 0.05), but soluble P-selectin and platelet count increased (P < 0.05). Posttreatment soluble P-selectin per platelet levels were higher than the normal values (P < 0.05). These results suggest that IL-6, soluble P-selectin, and soluble P-selectin per platelet are not responsible for the milder symptoms in chronic than in acute ITP. Mega-dose methylprednisolone seems to keep the soluble P-selectin levels elevated.     

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.     

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.     

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.     

Chronic immune thrombocytopenic purpura in children: a survey of the canadian experience

BACKGROUND: Immune thrombocytopenic purpura (ITP) in children is a common pediatric bleeding disorder with heterogeneous manifestations and a natural history that is not fully understood. To better understand the natural history of chronic ITP and detect response trends and outcomes of therapy, we conducted a 10-year retrospective survey of children from age 1 to 18 years with a diagnosis of chronic ITP. RESULTS: Data on 198 patients from 8 Canadian Pediatric Hematology/Oncology centers were analyzed. The majority of patients were female (58%), and were previously diagnosed with acute (primary) ITP (85%). The age at diagnosis of chronic ITP ranged from 1.1 to 17.2 years with a mean of 8.2+/-4.4 years. Ninety percent of patients received some form of treatment. Untreated patients had a higher mean platelet count at diagnosis of chronic ITP (P=0.009) despite similarities in mean age at first presentation and mean duration of follow-up. Thirty-four (17%) patients underwent splenectomy. Splenectomized patients tended to be significantly older, had a lower mean platelet count at diagnosis of chronic ITP, and had a longer duration of follow-up. CONCLUSIONS: The results from this study are consistent with published reports.     

儿童特发性血小板减少性紫癜病毒感染的临床分析

目的探讨儿童ITP病毒感染情况及其治疗与病情转归。方法(1)统计患儿发病的诱因,部分患儿检测EB病毒、巨细胞病毒、微小病毒B19、单纯疱疹病毒、支原体、自身抗体。分析病毒感染与ITP预后关系。(2)分析难治性与慢性TIP预后与治疗的关系。结果(1)病情严重程度与预后无关。(2)有特殊病毒感染诱因者共22例,其中12例(54.5%)为难治性或转为慢性;无特殊病毒感染诱因者共77例,其中19例(24.7%)为难治性或慢性,差异有显著性(P<0.05)。(3)难治性ITP转慢性的12例治疗效果均欠佳。(4)慢性ITP有特殊病毒感染者6例,其中好转的4例均多次短期大剂量应用丙种球蛋白,此4例中的3例同时或之前应用抗病毒药物,2例应用肾上腺皮质激素冲击。无特殊病毒感染史者13例,治疗好转6例,无效6例,均未应用大剂量丙种球蛋白。结论由特殊病毒感染引起的儿童ITP预后欠佳,加强联合大剂量丙种球蛋白、抗病毒的力度可改善预后。     

Intravenous immunoglobulin for idiopathic thrombocytopenic purpura (ITP) in childhood

IgG-SRK (identical with Sandoglobulin) is a polyvalent IgG concentrate obtained by modified alcohol cryoprecipitation, including mild acidification at pH 4. This product was given in high doses intravenously for the treatment of six children with acute ITP, four children with intermittent ITP, and three children with severe chronic idiopathic thrombocytopenic purpura (ITP). An impressive initial response was observed in all patients, the extent of which may be of prognostic significance in acute ITP. Maintenance therapy was required in two of six patients with acute ITP, in three out of four patients with intermittent ITP, and in all of the patients with severe chronic ITP. In the cases of severe chronic ITP, the disease could not be adequately controlled over long periods of time, but bleeding episodes subsided or became considerably less frequent. Although little is known of the effects of IgG-SRK, possible mechanisms were discussed. It is emphasized that a new model has been discovered to study the interrelations between structure and function of human immunoglobulin molecules.     

Infantile Idiopathic Thrombocytopenic Purpura

Idiopathic thrombocytopenic purpura (ITP) in childhood is a benign disease, as only 10% to 20% of (he patients have a chronic course. A retrospective study of 57 ITP patients ranging in age from four months to two years revealed that 30% of them proceeded to chronicity. Unlike ITP in the general pediatric population, chronic infantile ITP was characterized by male predominance, a high frequency of preceding viral infections, and lack of responsiveness to any of the known modalities of treatment.     

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.     

Management of human immunodeficiency virus-associated thrombocytopenia with intravenous gamma globulin

A 17-month-old boy in whom immune-mediated thrombocytopenia (ITP) was the presenting manifestation of infection with human immunodeficiency virus (HIV) is being successfully managed with intermittent high-dose intravenous gamma globulin (IVIG) allowing maintenance of hemostatic platelet counts while avoiding the immunosuppression associated with other therapeutic modalities used to treat ITP. He continues to demonstrate marked responsiveness to IVIG, and has been maintained on weekly or bimonthly infusions for 12 months. The serendipitous documentation of HIV infection prior to IVIG therapy for immune-mediated thrombocytopenia in this child documents the importance of HIV testing prior to IVIG therapy to prevent erroneous assignment of IVIG as the vehicle responsible for transmission of HIV infection. This case history also documents the importance of HIV testing in the diagnostic evaluation of immune-mediated thrombocytopenias.     

Anti-D immunoglobulin in the treatment of idiopathic thrombocytopenic purpura

Anti-D was evaluated in 8 RhD positive patients (6 males, 2 females) aged 2–21 years (mean 10 years) with idiopathic Thrombocytopenic Purpura (ITP). Five patients with chronic ITP and 3 patients with acute ITP were administered Anti-D in the dosage of 50 ug/kg intramuscularly (IM) for 3 consecutive days. One patient of chronic ITP received two courses of Anti-D. Patients were followed up for 7 to 16 months (mean 9 months). All three cases of acute ITP had a complete response and are in remission between 3 to 12 months of follow up. Two of five cases of chronic ITP had a partial response. Rise in platelet count was observed within 72–124 hours, and duration of response varied between 10 to 15 days. None of these patients had any significant side effects of anti-D immunoglobulin therapy. Intramuscular administration of anti-D is safe, effective and low cost alternative to IVlgG in the treatment of acute ITP.     

Immunthrombocytopenic purpura as a model for pathogenesis and treatment of autoimmunity

In honour of Professor Rossi's 80th birthday we review the development of our understanding of the immune and auto-immune nature of the pathogenesis of immune thrombocytopenic purpura (ITP). The immune aspects have been documented by postviral alterations of the cellular and humoral immune system, by new methods of specific auto-antibody detection against platelet glycoproteins and by the therapeutic effect of administering immunoglobulin concentrate from healthy blood donors. The various possible mechanisms of action of immunoglobulin treatment have led to use of this treatment as an alternative for other immune-related disorders. The treatment of severe chronic ITP in children, however, remains unsatisfactory. With a new international clinical and laboratory study of children and adolescents with early chronic ITP we are continuing the investigation of the pathogenesis and treatment of 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。     

Idiopathic thrombocytopenic purpura of childhood

Idiopathic thrombocytopenic purpura (ITP) is a benign hemorrhagic disorder characterised by peripheral thrombocytopenia and increased megakaryocytes in the bone marrow. The exact pathogenesis of ITP is not well understood. The adherence of viral induced immune complexes to the platelet membrane is thought to trigger the phagocytosis of damaged platelets by macrophages in the reticuloendothelial system. The role of platelet associated IgG in the pathogenesis of ITP is under investigation. Although spontaneous recovery is observed in 80–90% of patients, a short course of steroid therapy is recommended to reduce the duration of thrombocytopenia. The steroids however, have no influence on the course or outcome of the disease, and their possible role in reducing the incidence of intracranial hemorrhage (ICH) is unknown. Emergency management of patients presenting with signs and symptoms suggestive of ICH is essential to prevent the fatal outcome. Approximately 10–20% of patients develop chronic ITP. Splenectomy, considered the treatment of choice in these patients, is not always curative. The post-splenectomy sepsis also imposes a great risk for these individuals. Recent experience with intravenous immunoglobulin (IV IgG) treatment indicates that the splenectomy could safely be deferred, or even avoided in chronic ITP. The use of IV IgG in acute ITP is being investigated.     

Directions for research in autoimmune thrombocytopenic purpura (ITP)

All attendees participated in a round-table discussion regarding directions for research in autoimmune thrombocytopenic purpura (ITP). Suggested areas for study were grouped into five main areas: (i) improved classification of ITP identifying subsets of patients with differing clinical syndromes and response to treatment, and those more likely to have serious bleeding manifestations; identification of patients with reduced thrombopoiesis was emphasized; (ii) studies aimed at elucidating the aetiology and pathophysiology of ITP, with emphasis on distinctions between acute and chronic ITP and between patients responsive or refractory to therapy; these studies focused on measures of humoral and cellular immune dysregulation; (iii) studies of platelet function in ITP, with the intent of defining these abnormalities and correlating them with the clinical manifestations of the disease; (iv) new approaches to treatment, particularly of refractory patients; and (v) a miscellaneous group, which included development of an ITP registry, evaluation of the "burden" of disease, investigation of mood changes in ITP, etc. The discussion was not intended to be all-inclusive, but focused on the content of other talks in this symposium. It is hoped that some of thesesuggestions will be further developed for investigation in multicentre co-operative studies to improve the diagnosis, understanding and treatment of ITP.     

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。     

儿童人类免疫缺陷病毒相关性血小板减少性紫癜—附2例报告

目的通过两例人类免疫缺陷病毒相关免疫性血小板减少性紫癜(HIV-ITP)特点的临床总结及相关文献复习,提高对本病的认识。方法临床病历分析及文献复习。结果2例儿童分别经输血感染HIV后5年和7年后出现血小板减少性紫癜(ITP)的症状,经相关检测确诊为HIV-ITP,经丙球冲击及激素治疗好转,但很快复发。结论ITP是HIV病人常见的血液系统表现,也常是HIV的首发症状之一,抗ITP治疗短期有效,长期疗效不佳,彻底治愈困难。