Clinical effect of intravenous immunoglobulin on chronic idiopathic thrombocytopenic purpura

Summary High dose immunoglobulin infusions showed a marked effect on platelet counts in eight out of nine chronic ITP patients and in one SLE patient. In the comparison of different IgG-preparations, the pepsin treated IgG F (ab′)₂ showed no platelet elevation while the sulfonated did. The elevated platelet count could not be maintained after discontinuation of IgG infusions, but in six out of ten patients the platelet level remained above the pretreatment values. This new treatment seems to be safe and effective in adulthood ITP.     

Red cell sequestration during high dose intravenous immunoglobulin in idiopathic thrombocytopenic purpura

Summary The cellular interactions involved in the platelet response after immunoglobulin infusion in acute and chronic idiopathic thrombocytopenic purpura (ITP) are unknown. There have been a number of theories including the competitive inhibition of platelet-binding to macrophages by the preferential sequestration of immunoglobulin coated red cells. We report a study to examine this hypothesis. Adult acute and chronic patients were given infusions of immunoglobulin at a rate of 0.4 g/kg body weight, daily for 5 days. Serum haptoglobin, lactate dehydrogenase and the absolute reticulocyte counts were monitored and no significant change in any value was seen during the period of study. A red cell survival was performed on four of the patients and no increase in the rate of red cell clearance occurred during the infusion period. We conclude from this that in these patients no significant degree of haemolysis was provoked by the infusion although this does not preclude this as a mechanism of action in some individuals.     

Oral high-dose methylprednisolone and intravenous immunoglobulin treatments in adult chronic idiopathic thrombocytopenic purpura

Ten adult patient of chronic idiopathic thrombocytopenic purpura (CITP) used oral prednisone and were treated with seven doses of oral high-dose methylprednisolone (30 mg/kg). Nine of ten patients responded after HDMP treatment (plt > 150 × 10⁹/L). Two patients having 8 and 10 years of history achieved long-term remission after first HDMP treatment. One unresponsive and one responsive patients did not accept IVIG treatment as second therapy and lost the follow-up. The remaining six patients received IVIG (0.5 mg/kg for 5 days) as second therapy after 3 months. Platelet count increased above 150 × 10⁹/L in 4 patients and between 60–80 × 10⁹/L in 2 patients. The peak platelet counts of both therapy users were higher under HDMP than IVIG therapy (252 ± 110.4 vs 174.2 ± 83.7 × 10⁹/L), but the difference was not significant. Responses were transient and returned to pretreatment values at 14–30 days, excluding long-term remission of 2 (2/10) patients after HDMP treatment. No side effect was observed. Thus, oral HDMP appears a good initial therapy for continuous remission in a small ratio of patients and a good security for emergency situations and prior to surgery in adult CITP patients. Am. J. Hematol. 56:191–192, 1997. © 1997 Wiley-Liss, Inc.     

评价血小板相关抗体定量测定法对特发性血小板减少性紫癜的诊断价值

目的 :评价血小板相关抗体 (PAIg)定量测定法对诊断特发性血小板减少性紫癜 (ITP)的价值。 方法 :应用酶联免疫竞争抑制试验 (ELISA)定量测定血小板相关抗体 ,计算试验的灵敏度、特异度、准确度、阳性预测值 ,绘制受试者ROC曲线进行诊断价值的评价。结果 :根据常用判断PAIg阳性的临界值 ,血小板相关抗体试验诊断ITP的灵敏度较高 (95 % ) ,但特异度低 (48.8% ) ,准确度低 (5 7.5 % ) ,阳性预测值低 (30 .2 % )。用ROC曲线寻找诊断ITP的最佳临界值 ,用新的临界值 (PAIgG >16 0ng/10 7血小板或PAIgA >2 5ng/10 7或PAIgM >35ng/10 7)时 ,可提高诊断试验的特异度 ,从 4 8.8%提高到 6 2 .8% ,可确诊更多的患者 ;但准确度和阳性预测值仍低 ,分别为 6 7.9%和 36 .0 %。结论 :PAIg试验诊断ITP的特异度、准确度、阳性预测值较低 ,帮助诊断ITP的临床价值有限 ,即使用新的临界值提高了试验的特异度 ,但诊断ITP的价值仍不大。     

Polyclonal B-cell activation after intravenous immunoglobulin therapy in idiopathic thrombocytopenic purpura — an anti-idiotype response?

Polyclonal B cell activation occurred in 3 patients following treatment with intravenous immunoglobulin (i.v. Ig) for idiopathic thrombocytopenic purpura (ITP). The possibility that this may represent an anti-idiotype response and the hypothesis that prolonged remission of ITP may be induced by this mechanism are discussed.     

Pulsed intravenous high-dose dexamethasone in adults with chronic idiopathic thrombocytopenic purpura

The role of pulsed high-dose dexamethasone (DXM) in the treatment of patients with chronic idiopathic thrombocytopenic purpura (ITP) is still uncertain. Following an early report in which it was described as an effective and well-tolerated treatment with a sustained platelet response in 100% of cases, a number of subsequent studies have failed to confirm such favorable results. As all these studies were conducted on small numbers of patients, we investigated further the effectiveness and side effects of this therapeutic modality in a larger cohort. Thirty-two patients with chronic ITP were scheduled to receive six monthly courses of intravenous DXM at the dose of 40 mg/day for 4 consecutive days. All patients had ITP that had been resistant to between two and five different therapeutic regimens, including 9 patients who had already failed splenectomy. All patients had to be seen 2 weeks after each cycle to asses their response as well as secondary effects. Three patients failed to respond and clinically required other therapy. Thirteen patients (41%) had a partial (platelet count between 50 and 100 x 10(9)/liter) or complete (platelet count >100 x 10(9)/liter) response to treatment, responses being mostly transient. Responses were observed early during the course of treatment, usually right after the first cycle of DXM. There were no late responses. Side effects were mild and did not require discontinuation of treatment. No clinical or laboratory parameter was found to predict treatment outcome. We conclude that high-dose DXM has a limited effect in patients with chronic ITP. Novel approaches and controlled multicenter trials may help identify new therapeutic strategies for this disease.     

静脉输注丙种球蛋白治疗特发性血小板减少性紫癜

目的:分析静脉输注丙种球蛋白治疗特发性血小板减少性紫癜(ITP)的疗效。方法:静脉输注丙种球蛋白(IVIG)0.4g·kg-1·d-1,连用5d。结果:25例患者经治疗后,显效11例(44%),其中基本治愈5例(20%);良好效果6例(24%);进步4例(16%);无效4例(16%),总有效率为84%。结论:治疗重症、难治性ITP患者,IVIG是一种安全、有效、无不良反应的治疗方法。特别对≤14岁的患儿和初治病例疗效更佳。并可反复使用,复发患者用糖皮质激素治疗仍有效。     

High-dose intravenous IgG for chronic idiopathic thrombocytopenic purpura in adults

Summary Sixteen adult patients of mean age 48 years with chronic ITP were studied for platelet response to high-dose (0.4 g/kg body weight per day for five consecutive days) intravenous polyvalent intact IgG in the absence of any concurrent treatment. The platelet count returned to normal values in nine patients, a partial response (rise in the platelet count between 50 and 150 ×10⁹/l) was observed in three cases. One patient refractory to any other treatment went into a sustained remission. In the other responsive patients the response was only transient. Among seven splenectomised patients only three responded to IgG infusions versus nine in the non-splenectomised group. The length of ITP history appeared as a more critical factor for the response to IgG than previous splenectomy.     

Myelofibrosis and idiopathic thrombocytopenic purpura

 A case of idiopathic myelofibrosis (IMF) with concomitant autoimmune thrombocytopenic purpura (AITP) is reported. The literature on platelet antibodies in IMF is reviewed. Received: 25 March 1997 / Accepted: 11 July 1997     

Recurrence of thrombocytopenia in patients splenectomized for idiopathic thrombocytopenic purpura

Summary The effects of splenectomy in the treatment of chronic idiopathic thrombocytopenic purpura (ITP) were analysed in 177 subjects (118 adults and 59 children) operated upon between two and 25 years earlier.In 145 patients, thrombocytopenia regressed immediately or within 2 months after the operation. Regression of thrombocytopenia later during follow up was observed in a further 14 cases.Recurrence of thrombocytopenia after good immediate result of splenectomy developed in 32 patients. In 13 cases the recurrence was transient but in the remaining 19 patients it was long-lasting. In these cases presence of accessory spleens was suggested by the absence of Howell-Jolly bodies in the peripheral blood smear and demonstrated by splenic scan in 16 cases, and confirmed in 13 out of 15 splenectomized patients. Resplenectomy caused in 12 patients permanent disappearance of thrombocytopenia.     

Efficacy and response to intravenous anti-D immunoglobulin in chronic idiopathic thrombocytopenic purpura

This review explored the effectiveness of anti-D in the management of chronic idiopathic thrombocytopenic purpura (ITP). Of 16 patients, 14 non-splenectomized and two splenectomized, with chronic ITP received anti-D immunoglobulin at a dose of 50-75 mcg/kg. A total number of 100 doses anti-D were given. Fourteen patients had previous treatment with steroids, which was discontinued either because of unresponsiveness or unacceptably high maintenance doses. Two patients had no previous treatments with any modality. Anti-D was given as a short i.v. infusion whenever platelet count dropped below 30 x 10(9)/l or patient was haemorrhagic or preoperatively. Response was defined as an absolute platelet count >30 x 10(9)/l or an increment by > or =20 x 10(9)/l. Response was obtained in 14 patients with a response rate of 87%. Fifteen patients were not on any other form of treatment at the time of anti-D therapy and one patient had a concurrent steroid therapy. The improvement in platelet count lasted for more than 8 weeks post-57% of anti-D infusions. We report two patients with previous splenectomy for ITP who responded to anti-D therapy. The side-effects profile was very mild with no patients required red cell transfusion.     

抗幽门螺杆菌治疗对慢性特发性血小板减少性紫癜患者疗效观察

目的通过对特发性血小板减少性紫癜(ITP)患者行抗幽门螺杆菌(HP)感染的临床研究,观察ITP与HP感染之间的关系以及抗HP在ITP患者治疗中的作用。方法2003-07~2003-12对解放军301医院17例慢性ITP患者采用14C尿素呼气试验进行HP检测,女11例,男6例,病程4个月至8年,并对阳性患者行奥美拉唑、克拉霉素及阿莫西林三联根除HP治疗,观察血小板情况。结果本组17例患者中HP阳性13例,阴性4例,抗HP后转阴11例,其中8例血小板水平较前有所提高。结论抗HP治疗确实可提高部分慢性ITP患者的血小板数。     

High-dose dexamethasone therapy in chronic idiopathic thrombocytopenic purpura

 A high-dose pulse of dexamethasone has been described as a current option for the treatment of refractory idiopathic thrombocytopenic purpura (ITP), but the results are controversial. Here we describe the use of a high dose of dexamethasone (40 mg per day for 4 days every month) in 18 patients with chronic ITP. The median age of the patients was 42.5 years (range, 16–77 years); 13 were female and five male. The duration of the disease ranged from 5 to 480 months, and splenectomy was carried out in six of the 18 patients.The overall results obtained revealed a satisfactory response (platelet counts higher than 50×10⁹/l) in eight of the 18 patients. However, a long-term remisson was achieved in only three of the eight patients with a follow up of 7–16 months. We were not able to identify any clinical or laboratory prognostic parameters or previous treatment which would allow one to predict a successful outcome of this treatment. These results suggest that a high dose of dexamethasone may provide an alternative, be it a poor one, for the treatment of refractory IPT, in which the use of a low-cost drug with limited side effects is an important consideration. Received: 18 March 1996 / Accepted: 2 July 1996     

Persistent remission of adult chronic autoimmune thrombocytopenic purpura after treatment with high-dose intravenous immunoglobulin

Transient efficacy of high-dose intravenous immunoglobulin infusions (HDI) is widely demonstrated in autoimmune thrombocytopenic purpura (AITP). A trial involving repeated injections of HDI was conducted in two adult patients with chronic AITP in order to evaluate their long-term efficacy in refractory forms and their ability to obviate splenectomy. Both patients received 2 g/kg body weight of polyvalent intact intravenous immunoglobulin followed by seven and eight boosters (0.8 to 1.2 g/kg body weight) when the platelet count decreased. It was found that the injections could be spaced progressively. The platelet count remained normal 200 and 800 days after the end of the treatment. The demonstration of the possible long-term efficacy of repeated injections of intravenous immunoglobulin encourages us to recommend this safe therapy for patients with chronic AITP.     

Intravenous immunoglobulin and autoimmune thrombocytopenic purpura: 22 years on

Autoimmune thrombocytopenic purpura is now commonly treated with high doses of intravenous immunoglobulins. Twenty-two years after this treatment was first shown to be effective, several questions remain. We review here current knowledge concerning the frequency and type of side-effects and the probable mechanism of action of intravenous immunoglobulins. We suggest that the currently recommended dose of intravenous immunoglobulins (2 g/kg body weight) could be halved, that the total dose of intravenous immunoglobulins should be administered as a single infusion, that non-responders could be given another equal dose on day 3, and that intravenous immunoglobulins plus prednisolone should be considered as the gold standard for treatment of the most severe forms of the disease. Finally, as intravenous immunoglobulins have only a transient effect, they cannot be considered as a curative treatment for patients with chronic autoimmune thrombocytopenic purpura.     

糖皮质激素治疗慢性特发性血小板减少性紫癜疗效相关因素分析

目的：探讨影响糖皮质激素治疗慢性特发性血小板减少性紫癜疗效的有关因素。方法：采用Logistic回归对74例经糖皮质激素治疗的慢性特发性血小板减少性紫癜患者性别、年龄、是否并发除皮肤出血以外较严重的出血表现、起病至开始治疗时间、是否有脾脏肿大、是否并发肝炎病毒感染、治疗前血小板计数、骨髓巨核细胞数8项因素进行多因素分析。结果：起病至开始治疗时间，是否并发肝炎病毒感染，骨髓巨核细胞数是影响糖皮质激素治疗慢性特发性血小板减少性紫癜疗效的相关因素。结论：分析患者治疗前各项可能影响疗效的相关因素，对于指导慢性特发性血小板减少性紫癜治疗方案的选择，尤其是合理掌握糖皮质激素的使用时间有重要意义。     

High-dose dexamethasone as a first- and second-line treatment of idiopathic thrombocytopenic purpura in adults

The current first-line choice of treatment of idiopathic thrombocytopenic purpura (ITP) in adults, prednisone, is effective but has many side effects. Furthermore, reduction of the dose leads to a relapse of ITP in a majority of cases. Courses of high-dose dexamethasone (HD) aim to avoid these problems. We treated 36 patients with newly diagnosed or recurrent ITP with an 8-day course of HD, with a peak dose of 40 mg/day. The courses were repeated up to a maximum of six courses, with a 28-day interval. Acute and chronic effects of HD on platelet counts were observed, as well as side effects. HD led to an acute response (rise of platelet count to a level above 50×10⁹/l) in 83%. When HD was given as a first-line treatment, 59% of patients were still in remission after 31 months. When HD was given as a second-line treatment, 50% of patients were in remission after 5 months, declining to 25% after 54 months. Side effects were frequent but rarely dangerous. In conclusion, acute effects of HD were excellent. Long-term effects of HD as a first-line therapy of ITP were good, but its long-term effects as a second-line therapy were much poorer.     

Rituximab chimeric anti-CD20 monoclonal antibody treatment for adult refractory idiopathic thrombocytopenic purpura

Idiopathic thrombocytopenic purpura is an autoimmune disease which involves opsonization of platelets by autoantibodies directed against different surface glycoproteins, leading to their premature destruction by the reticuloendothelial system. Management of patients with refractory ITP is difficult. Recent studies have shown that rituximab, a chimeric anti-CD20 monoclonal antibody, is useful in the treatment of these patients, with overall response rates of about 50%. Most published reports have included a small number patients including case reports. The present study reports the results of a retrospective Danish multicenter study of rituximab in the treatment of adult patients with refractory ITP. Thirty-five patients (median age 52 years, range 17-82 years, 17 males) were included. One patient had immune thrombocytopenia and neutropenia. All patients had received prednisolone (Pred). Next to Pred, 25 patients had been treated with high-dose IgG, and in 16 patients a splenectomy had been performed. Sixteen patients had been treated with azathioprine. Other treatments included, e.g., cyclosporine, danazol, cyclophosphamide, vincristine, interferon, and dexamethasone. The patients were treated with a dose regimen of 375 mg/m2 i.v. approximately once weekly for 4 consecutive weeks. Six patients received a fixed dose of 500 mg disregarding their weight supplemented by 100 mg of methylprednisone i.v. or 50-100 mg of Pred given as premedication together with an antihistamine just before infusion of rituximab. The large majority of patients also received Pred and, in some cases, other concomitant immunosuppressive treatment during part of their rituximab treatment. A complete response (CR) was defined as a rise in the platelet count > 100 x 10(9)/L, a partial response (PR) as a rise in the platelet count > 50 x 10(9)/L, and a minor response (MR) as a rise in the platelet count < 50 x 10(9)/L. No response (NR) was defined as no increase in the platelet count. Because 4 patients were treated twice, a total of 39 outcomes of rituximab treatment were evaluated. Rituximab proved to be effective in 17 of 39 treatments [overall response 44% with 7 CR (18%) (1 patient showed a CR twice), 6 PR (15%), and 4 MR (10%)]. In 9/13 cases of CR or PR, the response (platelet level > 50 x 10(9)/L) was prompt, 1-2 weeks after the first infusion. The remaining patients responded 3-8 weeks later. Patients with CR and PR have been in remission for a median of 47 weeks. In general the side effects were few. In 2 cases, the treatment was stopped because of side effects either during or after the first infusion. Two fatal outcomes were recorded. A 71-year-old female with severe lung disease died 6 days after the first infusion of respiratory failure. The other patient, a 73-year-old man also with severe chronic obstructive lung disease, died of pneumonia approximately 13 weeks following the last rituximab treatment. It is concluded that rituximab may be a useful alternative therapy in patients with severe and symptomatic ITP refractory to conventional treatment.     

Platelet recovery in patients with idiopathic thrombocytopenic purpura after eradication of Helicobacter pylori

The relationship between Helicobacter pylori infection and idiopathic thrombocytopenic purpura (ITP) has been investigated in several studies. We investigated the prevalence of H. pylori infection and the clinical effects of eradication in 22 Japanese patients with chronic ITP. H. pylori infection was found in 14 (63.6%) of the patients by histologic and culture examinations of biopsy samples obtained by gastrointestinal endoscopy. H. pylori was eradicated by proton pump inhibitors and 2 kinds of antibiotics in 13 (92.9%) of the 14 patients in whom the results of treatment could be evaluated. Five (38.4%) of those 13 patients had platelet recovery (platelet count of more than 100 x 10(9)/L and an increase of more than 30 x 10(9)/L with respect to the baseline value) after eradication. The median follow-up period was 15 months. One patient who had a complete response had a partial relapse after cessation of prednisolone treatment without any evidence of H. pylori reinfection. Another patient, in whom H. pylori was not eradicated even after 2 treatment sessions, had a partial response after treatment. A screening examination for H. pylori infection may be necessary for Japanese patients with newly diagnosed ITP. Although the exact mechanism underlying platelet recovery after H. pylori eradication is not clear, the results of this study indicated that H. pylori eradication treatment is a good option for some patients with chronic ITP.