High-dose intravenous methylprednisolone for acute childhood idiopathic thrombocytopenic purpura

49 children with acute idiopathic thrombocytopenic purpura (ITP) were divided into non-treatment, oral prednisone (2 mg/kg), and high-dose intravenous methylprednisolone (HIVMP) treatment groups which consisted of 17, 16 and 16 children respectively. Platelet counts rose above 150,000/microliters over a 2-week period in 5 (29.4%) children in the first group, 5 (31.2%) in the second group and 15 (93.7%) children in the third group. Platelet counts reached the normal level in only 3 days in 11 (68.7%) children treated with HIVMP. Initially, antiplatelet antibodies (APA) were shown by the Handin and Stossel method in every patient. With normalization of platelet counts, the antibodies decreased but could still be detected in every case; antibody decrease was greater in the HIVMP group. With the exception of mild cushingoid appearance, none of the major corticosteroid side effects was observed in the treated children.     

Prevention of chronic ITP?

Summary The treatment of childhood ITP with IVIG has been widely used in acute or in previously treatment-dependent, chronic forms of the disease. We discuss propositions of a prospective multicenter study to evaluate the efficacy of IVIG to prevent the development of chronic ITP in childhood. The problems of such a study, i.e. evaluation criteria, number (about 10% of patients with acute ITP will develop the chronic form) and related topics are discussed.Presented at the International Workshop on ITP, August 26 and 27, 1988, Lucerne, Switzerland     

Platelet associated IgG, platelet mean life span and treatment with intravenous immunoglobulin in idiopathic thrombocytopenic purpura

The clinical significance of platelet associated IgG in ITP detected by direct platelet suspension immunofluorescence test (PSIFT) was studied. The platelet mean life span (MLS) was measured with 111In-labelled platelets in 17 adult patients. All the patients had shortened platelet MLS. The direct PSIFT was positive in 14 patients. Patients were initially treated with prednisone; 12 patients with poor response to the drug were splenectomised. 8 of these 12 patients were treated with intravenous immunoglobulin (IvIg) before splenectomy. The response to IvIg was as good or better in the 3 patients with negative PSIFT, than in the 5 patients with positive PSIFT.     

ITP in pregnancy: Use of the bleeding time as an indicator for treatment

Summary ITP is a relatively common disorder seen in pregnancy. Current recommendations for management of patient with ITP recommend maintaining the platelet count above 50×10⁹/L and the bleeding time less than 20 min. It has been well documented that the bleeding time in ITP is disproportionately shortened in many patients relative to the platelet count. We present a prospective study of 24 ITP patients in whom the bleeding time was used as an indicator for therapeutic intervention in pregnancy. Indications for therapy with prednisone and/or intravenous gammaglobulin were the following: significant clinical hemorrhage due to thrombocytopenia; bleeding time of greater than 20 min at the baseline platelet count; for normalization of hemostasis prior to delivery or surgical procedure. Caesarean section was performed only in cases in which there were obstetrical indications for this mode of delivery or when the fetal platelet count (obtained by fetal scalp vein sample) was less than 50×10⁹/L. Of 24 patients with ITP, eight had significant thrombocytopenia (platelet count less than 50×10⁹/L) throughout pregnancy. Only two patients required prolonged prednisone therapy. Both suffered side effects of chronic prednisone administration. Four patients were treated with prednisone for a short course (10–14 days) at term to improve hemostasis for delivery. One patient was treated with intravenous gammaglobulin at term in an effort to prevent severe neonatal thrombocytopenia. Seven patients required caesarean section; the remaining 17 patients underwent vaginal delivery. Only one minor bleeding complication was seen — a small wound hematoma post caesarean section. In summary, using the bleeding time as an indiator for therapeutic inervention, treatment of ITP in pregnancy can be minimized. Thus, therapy related toxicity can be avoided.Presented at the International Workshop on ITP, August 26 and 27, 1988, Lucerne, Switzerland     

不同脾蒂离断法在腹腔镜脾切除治疗ITP中的成本-效果比较

目的 比较腹腔镜下原位二级脾蒂离断法脾切除术(laparoseopic splenectomy by secondary pedicle division,LSSP)和腹腔镜下直线切割闭合器脾切除术(laparoscopic splenectomy by Endo-GIA.LSED)治疗特发性血小板减少性紫癜(idio...     

Rituximab in the management of chronic immune thrombocytopenic purpura: an effective and safe therapeutic alternative in refractory patients

Rituximab induces B-cell depletion; therefore, it has been used in the treatment of immune thrombocytopenic purpura (ITP). The aim of this retrospective study was to evaluate the effectiveness of rituximab in the treatment of 89 patients with chronic ITP refractory to several treatments. All the patients had platelet counts <30×10⁹/l. They had received a median of five (2–13) previous treatments, and 47 had undergone splenectomy. Rituximab was administered i.v. at 375 mg/m² in four weekly doses in 77 patients, and 12 patients received 1–6 doses. Forty-nine patients (55.1%) reached platelet counts >50×10⁹/l; 41 (46%) achieved a complete response (CR; platelets >100×10⁹/l), and eight (9%) obtained a partial response (platelets 50–100×10⁹/l). Overall, 31 patients (35%) maintained response, including 15 patients in whom splenectomy failed, with a median follow-up of 9 months (2–42), 12 for more than 1 year. The unique predictor of a maintained response was to reach a CR. Heavily treated patients (more than three different previous treatments, including any corticosteroids) and those with longer ITP duration (>10 years from diagnosis) had a worse response. Non-splenectomized patients had a better early response rate than those splenectomized. Rituximab was well tolerated, with two fever episodes following infusion and two reports of skin rash. Rituximab induced clinical responses in multi-treated refractory ITP patients with little toxicity and should be considered as an early therapeutic option in this setting, even as an alternative to splenectomy in selected patients.An erratum to this article can be found at     

龙丹生血颗粒对免疫性血小板减少性紫癜模型小鼠外周血象与骨髓巨核细胞以及血清PAIgG水平的影响

目的 观察龙丹生血颗粒对ITP模型小鼠骨髓巨核细胞和血清PAIgG的影响.方法 70只Balb/c小鼠随机分为对照、模型、升血小板胶囊、泼尼松、龙丹生血颗粒大、中、小剂量7组,除正常组外,其余各组隔日1次腹腔注射豚鼠抗小鼠血小板血清（GP-APS）建立ITP小鼠模型,于造模第8天开始给药,各组均按0.2ml/（10g·d）体积灌胃.其中,正常组、模型组灌服生理盐水,升血小板胶囊组灌胃升血小板胶囊内容物混悬液1.125g/kg,泼尼松按0.0113mg/（10g·d）灌胃,龙丹生血颗粒大、中、小剂量组分别按13.75g生药/千克、6.88g生药/千克、3.44g生药/千克灌胃.连续8天后眼球取血分离血清,进行血液学、血清PAIgG检测,并观察小鼠骨髓巨核细胞形态及分类.结果 与正常组相比,模型组小鼠PLT、WBC、Hb降低,血清PAIgG明显升高,骨髓产板巨核细胞数减低.与模型组相比,龙丹生血颗粒各剂量组小鼠外周血PLT、WBC、Hb数值均有所恢复.大剂量组产板巨核细胞明显增加,PAIgG有所降低.结论 龙丹生血颗粒通过降低血清PAIgG水平、促进骨髓巨核细胞分化而提升ITP模型动物外周血小板数值.     

CD47 is expressed at normal levels in patients with autoimmune haemolytic anaemia and/or immune thrombocytopenia

CD47 deficiency results in lethal autoimmune haemolytic anaemia (AIHA) and mild spontaneous thrombocytopenia in non-obese diabetic mice. It is unknown whether CD47 has an impact on AIHA of the warm type or autoimmune thrombocytopenia (ITP) in humans. Healthy blood donors (n= 11), patients with AIHA (n= 13), patients with ITP (n= 18) and one patient with Rh(null) phenotype were investigated. CD47 expression on red blood cells (RBC), platelets, granulocytes and lymphocytes and in plasma was determined by quantitative flow cytometry. All types of blood cells studied were found to carry CD47. Although CD47 expression on Rh(null) RBCs was decreased, there was no significant difference between CD47 expression on RBCs of healthy blood donors and on those of patients with AIHA or ITP. Similarly, CD47 was detectable in the plasma of the studied subjects. No evidence for a pathogenetic role of CD47 in autoimmune haemolysis or thrombocytopenia in humans could be demonstrated.     

Efficacy and safety of anti-D for treatment of adults with immune thrombocytopenia

This study was planned to assess the response of anti-D in patients with immune thrombocytopenia (ITP). Twenty adults (8 males: 12 females) with a median age 33.5 years (19–59 years) were included. Nine patients had newly-diagnosed ITP, 6 had persistent ITP and 5 had chronic ITP. The overall response rate was 65%. Patients with newly diagnosed ITP showed response rates of 77% (7/9), persistent ITP had response rates 50% (3/6) and patients with chronic ITP had response rates of 60% (3/5). The median time to response was 3 days (1–11 days). There was no correlation of response with age, sex, severity of bleeding, presenting platelet counts, ABO blood group or prior steroid or IVIG response.     

Bayesian Adaptive D-Optimal Design with Delayed Responses

In some disease areas such as diabetes and obesity, patients may need to be studied for several weeks or months for a drug effect to emerge, where longitudinal data are normally collected for each patient. These delayed responses provide challenges to current adaptive design methods. Fu and Manner (2010 Fu , H. , Manner , D. ( 2010 ). Bayesian adaptive dose-finding studies with delayed responses . Journal of Biopharmaceutical Statistics 20 : 1055 – 1070 .[Taylor &; Francis Online], [Web of Science ®] , [Google Scholar]) provided an integrated two-component prediction (ITP) model for delayed response adaptive design. In this paper, we extend their ITP model to incorporate a dose-response model in it and propose an ITP Emax model. Furthermore, we propose a utility function for decision making and this utility function is based on D-optimal design theory. We demonstrate our method by a simulation study, and potential sample size reduction is also discussed.