Long-term follow-up of autoimmune thrombocytopenic purpura (ATP) patients submitted to splenectomy

We studied the general outcome in 94 adult patients with autoimmune thrombocytopenic purpura (ATP) submitted to splenectomy. Of 84/94 patients who presented a complete or partial response 30 d after splenectomy, 16 (19%) showed one or more relapses. The clinical situation of the 81 patients still under observation is as follows: 13 unresponsive, 60 completely or partially responsive, without relapses during the follow-up, 8 completely or partially responsive after one or more relapses. No correlation was found between the favourable splenectomy outcome and age at splenectomy, the diagnosis-splenectomy interval and initial response to corticosteroids. The probability of disease-free survival is 83%, projected at 10 yr, while the overall survival is 93%, projected at 10 yr. PAIgG levels of the normal subjects and of responding patients were found to be similar, while in the groups of non-responding/relapsing patients, significantly higher values of PAIgG were detected, as compared to the control group.     

Long-term follow-up of chronic autoimmune thrombocytopenic purpura refractory to splenectomy: a prospective analysis

Splenectomy remains the most effective treatment of chronic autoimmune idiopathic thrombocytopenia (ITP) (i.e. of > 6 months duration). Treatment of patients refractory to splenectomy (with absence of response or relapse after initial response) is difficult, and their long-term outcome is not well known. Over a 10-year period, 183 patients with chronic ITP were splenectomized including 158 adults and 25 children ( 100 x 10(9)/l, nine of them without treatment and 27 of them with low-dose steroids or azathioprine; six (13%) remained moderately thrombocytopenic (35 x 10(9)/l to 100 x 10(9)/l platelets); the last five patients, without response to any treatment (up to six regimens), remained severely thrombocytopenic (platelets < 20 x 10(9)/l), and three of them died from bleeding. Twenty-seven (57%) of the 47 refractory cases required at least one hospitalization, in the majority of cases for intravenous immunoglobulin (IVIg) infusions. Seven of the refractory cases occurred in children. Six of them subsequently reached platelet counts > 100 x 10(9)/l, but one died from bleeding. Our findings confirm the overall favourable long-term prognosis of chronic ITP refractory to splenectomy.     

The response to high-dose intravenous immunoglobulin or steroids is not predictive of outcome after splenectomy in adults with autoimmune thrombocytopenic purpura

The response to high-dose intravenous immunoglobulin (IVIg) was recently reported to be predictive of outcome after splenectomy in patients with autoimmune thrombocytopenic purpura (AITP). We analysed the records of 75 adults with chronic AITP who received IVIg and subsequently underwent splenectomy. There was no significant difference in the response rate to splenectomy according to whether or not patients had responded to IVIg (81% v 67%, P = 0.36). Age, the time from diagnosis to splenectomy, and the response to steroids were also not significantly associated with outcome after splenectomy. These results indicate that the response to IVIg or steroids is not predictive of the efficacy of splenectomy.     

Reevaluation of the prognostic factors for splenectomy in chronic idiopathic thrombocytopenic purpura (ITP): a report on 181 cases

From 1973 to 1986 we splenectomized 181 patients with chronic ITP after platelet kinetic studies with 51Cr or 111In. Mean age at diagnosis was 34 (range 4-79 yr). Follow-up of at least 1 yr after splenectomy was available in every patient. 141 patients (78%) achieved remission (platelets greater than 100 x 10(9)/l by 3 months after splenectomy), of whom 9 subsequently relapsed. Among the 40 non-responders at 3 months, 3 achieved a later remission spontaneously. Factors associated with response to splenectomy included a high post-operative platelet count (p = 0.0001), younger age at the time of surgery (p = 0.0077) and predominantly splenic sequestration of platelets (p = 0.0002), the two latter factors being partially correlated. In a multivariate analysis, however, only post-operative platelet count and age retained an independent prognostic significance, whereas the sequestration site of platelets had only borderline value. These results are discussed in the context of indications of platelet kinetic studies in chronic ITP, before splenectomy is considered.     

Effect of Helicobacter pylori eradication on platelet recovery in Japanese patients with chronic idiopathic thrombocytopenic purpura and secondary autoimmune thrombocytopenic purpura

The prevalence of Helicobacter pylori infection and the effect of its eradication on platelet count in 48 Japanese patients with autoimmune thrombocytopenic purpura (AITP), including 40 chronic idiopathic thrombocytopenic purpura (ITP) and eight secondary AITP, were investigated. H. pylori infection was found in 25 ITP patients (62.5%) and in two secondary AITP (25%). H.pylori eradication was obtained in 19 of 19 infected ITP patients (100%), who were not in remission (platelets < 100 x 109/l) at the time of infection assessment. During follow-up (median 14.8 months), 12 of 19 H. pylori-eradicated patients (63.2%) showed a significant increase in platelet count accompanied by a significant decrease of platelet-associated immunoglobulin G (IgG). This response was maintained in all responding patients throughout the follow-up period. However, two infected patients with secondary AITP did not show platelet increase after eradication. The assessment of H. pylori infection and its eradication should be attempted in ITP as this approach could be an effective strategy, at least for some of these patients.     

Thrombotic thrombocytopenic purpura in autoimmune hepatitis

Received: July 17, 2000 / Accepted: August 25, 2000     

Dapsone for chronic autoimmune thrombocytopenic purpura: a report of 66 cases

Sixty-six adults with chronic autoimmune thrombocytopenic purpura AITP and platelet count <50 ×10⁹ l were treated with dapsone (75–100 mg orally). A response was observed in 33 patients. The median duration of treatment required to obtain a response was 21 d (range 8–90). The median maximal platelet count on treatment was 130 × 10⁹ l (range 71–355). Dapsone was continued in 20/33 responders for a median of 12.5 months (range 1–48) and the response persisted in 19. Treatment was intentionally withdrawn in the other 13 responders and thrombocytopenia immediately recurred in 12. Reversible side-effects required cessation of treatment in seven patients. These results demonstrate that dapsone is an effective, inexpensive, and well-tolerated treatment for chronic AITP.     

Response to splenectomy is durable after a certain point in time in adult patients with chronic immune thrombocytopenic purpura

Splenectomy may lead to a good response in 60-80% of adult patients with corticosteroid refractory idiopathic thrombocytopenic purpura (ITP) but, the long-term response to splenectomy still remains less well defined. We assessed the long-term efficacy and safety of splenectomy in adult patients with chronic ITP. A cohort of 59 splenectomised ITP patients (M/F = 25/34; median age 39 yr; range 14-75) were followed up for a median of 18 yr (range 2-32). No life-threatening surgical complications were observed. The overall response rate was 78% with 59% complete remission (CR) and 19% partial remission (PR). CR and PR patients were younger than non-responding patients at time of diagnosis (median age: 36 yr vs 48 yr, P = 0.03) and at splenectomy (median age: 38 yr vs 51 yr, P = 0.02). Among the 46 responding patients, eventually 17 had relapse. No disease progression occurred after 12.1 and 7.3 yr for patients in CR or PR, respectively. One case of fatal septicaemia was recorded. We conclude that splenectomy is an effective and safe treatment in adult patients with chronic ITP failing to respond to corticosteroid treatment and importantly, our findings support the view that response to splenectomy is durable after a certain point in time.     

Persistent lymphocytosis of natural killer cells in autoimmune thrombocytopenic purpura (ATP) patients after splenectomy

We report three patients with primary autoimmune thrombocytopenic purpura (ATP) who developed an absolute lymphocytosis (lymphocyte count > 5×10⁹/I) after splenectomy and with a lymphocyte count between 5.4 and 8.9×10⁹/I. An immunophenotype study showed that the peripheral blood lymphocytosis was a persistent NK cell expansion (CD2⁺, CD56⁺, CD3^-), and was characterized by a typical large granular lymphocytes (LGL) morphology. Two of these three ATP patients were refractory to splenectomy.     

The use of vinca alkaloids in preparation for splenectomy of corticosteroid refractory chronic immune thrombocytopenic purpura patients

Administration of vinca alkaloids (VA) to chronic corticosteroid refractory immune thrombocytopenia (ITP) patients results in a temporary increase of platelet count. The aim of the study was to evaluate the efficacy of vinca alkaloids in preparing adult corticosteroid refractory chronic ITP patients for splenectomy as well as to compare the costs of this method with costs of applying intravenous immunoglobulins. The study included 12 chronic ITP patients refractory to corticosteroids applied for 3-144 months. The patients were prepared for splenectomy with average 3.0 (from 1 to 4) 2-h intravenous infusions of vinca alkaloids at 7 day intervals. In eight patients, vincristin was used in a total dose of 6 mg (2 mg per infusion), in two patients, vinblastin was used in total dose of 30 mg (10 mg per infusion), and in two patients, vincristin and vinblastin infusions were administered alternatively. In nine of the 12 treated patients (75%) the platelet count increased to > or = 80 x 10(9)/l, which allowed safe splenectomy. Three patients unreactive to VA treatment were prepared for splenectomy with intravenous gammaglobulin infusions. Splenectomy was performed in 12 patients, in eight with laparoscopic method, in four with classic method. No complications during surgical intervention were observed. In none of the VA treated patients was myelosupression or liver or/and kidney dysfunction observed. Splenectomy resulted in normalization of platelet count in all patients after operation and in six of nine patients followed up for 10 months (on the average). Matching of VA costs with treatment efficacy and comparison with similar costs for intravenous immunoglobulin treatment revealed many fold lower costs of the former method.     

Clinically significant newly presenting autoimmune thrombocytopenic purpura in adults: a prospective study of a population-based cohort of 245 patients

The true incidence and prognosis of autoimmune thrombocytopenic purpura (ITP) in adults is unknown. We present the results of a prospective study in a population-based cohort of newly presenting adults (> or = 16 years) with ITP and platelet count of < 50 x 109/l, which took place between 1 January 1993 and 31 December 1999 in the former Northern Health Region in the UK (population 3.08 million). A total of 245 cases were confirmed by bone marrow examination with a median follow-up of 60 months (range 6-78 months). There were 134 females/111 males (1.2:1). Overall incidence was 1.6 per 105 per annum. Absolute incidence was similar for both sexes, with highest age-specific incidence in those aged > 60 years. Thirty patients (12%) presented with frank bleeding, and 28% were asymptomatic. Forty-five patients (18%) received no treatment, and 135 (55%) received first-line treatment only. Thirty patients (12%) underwent splenectomy. There were four deaths (1.6%) from bleeding and/or the complications of therapy in this cohort, but only one was in the acute phase of the illness. The majority of patients (155 out of 245) achieved remission (platelet count > 100 x 109/l), with a further 59 (24%) in partial remission with no symptoms (platelet count 30-100 x 109/l). This population-based study suggests that the traditional view of adult ITP as being a predominantly chronic disease that preferentially affects females needs to be modified.     

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.     

Primary biliary cirrhosis presenting as idiopathic thrombocytopenic purpura with deterioration after splenectomy

A case of primary biliary cirrhosis (PBC) presenting as idiopathic thrombocytopenic purpura is described. The patient, a 59-year-old woman, had, at the time when thrombocytopenia was first observed, an asymptomatic PBC. She responded only temporarily to corticosteroids, and splenectomy had to be performed later. After this operation the platelet count was normalized, but a marked and rapid deterioration of her previously indolent PBC occurred. The time-relationship indicates that the removal of the spleen may be considered the cause of the disease's progression. Possible mechanisms behind this adverse effect of the splenectomy are discussed. After initiation of azathioprine therapy a good response in clinical and laboratory features of the PBC was obtained, although the histological picture has remained unchanged.     

Analysis of outcome of laparoscopic splenectomy for idiopathic thrombocytopenic purpura by platelet count

Laparoscopic splenectomy (LS) is now performed routinely in patients with idiopathic thrombocytopenic purpura (ITP) refractory to the medical treatment. Low preoperative platelet count was deemed to be a contraindication for a laparoscopic approach; however, there is no data reporting the outcome in those patients. We aimed to evaluate the influence of the preoperative platelet count on the operative and postoperative course and complication rate. Retrospective cohort study that was conducted in tertiary care university-affiliated medical center and included 110 consecutive patients who underwent LS. All patients were divided into three groups by their preoperative platelet counts: 50 x 10(9)/L (n = 80). The outcome and the influence of preoperative factors predictive of complications, blood transfusion, and length of stay were compared between the groups. Patients with a platelet count of 20 x 10(9)/L before surgery. Patients with counts >20 x 10(9)/L can safely undergo LS.     

脾切除治疗特发性血小板减少性紫癜的疗效观察及预后因素分析

目的:评价脾切除治疗特发性血小板减少性紫癜(ITP)的治疗效果,探讨影响脾切除治疗ITP预后的相关因素。方法:对52例ITP患者进行回顾性分析,应用SPSS统计软件首先做单因素分析,将单因素分析后P<0.05的预后因素进行Logistic回归分析,筛选出独立的预后因素。结果:本组52例患者随访4～118个月,67.3%患者获得显效,17.3%为良效,15.4%为无效,总有效率为84.6%;单因素分析显示,年龄、术前血小板计数及术后1周内血小板计数峰值对脾切除治疗ITP的预后有显著影响。Logistic回归分析示年龄是判断脾切除疗效的独立预后因素。通过构建的预后方程进行效能评价,显效组和非显效组的评分差异有统计学意义。结论:脾切除治疗ITP是一种安全有效的治疗方法,年龄是判断脾切除治疗ITP疗效的独立预后因素,本组构建的预后方程能较好地反映预后,对临床指导有一定价值。     

A simple method for detecting complement-fixation by autologous platelets in autoimmune thrombocytopenic purpura

Summary A new modification of the microtitre complement fixation test, (CFT), is described for the detection of platelet-bound antibodies (PBA). The test was positive in 12 out of 16 patients, (75%), with active autoimmune thrombocytopenic purpura (AITP). It was negative in four patients who were in remission of AITP when tested, in 10 patients with non-immune thrombocytopenia and in 51 normal blood donors. This is a semi-quantitative method in which suspensions of the patients' own platelets consume complement and therefore prevent the lysis of sensitised sheep red cells (SRBC). Sera from some of these cases were also tested for serum anti-platelet antibody (SPA) and immune complexes. The possible mechanisms and the relevance of positive results are discussed.     

Serum leptin levels in patients with idiopathic thrombocytopenic purpura

OBJECTIVES: The purpose of this study was to evaluate serum leptin levels in idiopathic thrombocytopenic purpura (ITP), in order to determine the influence of leptin on the pathogenesis of ITP. SUBJECTS AND METHODS: Forty-six untreated patients with chronic ITP were compared with 40 healthy people of similar age, sex and body mass index (BMI). Serum leptin levels (ng/mL) were measured by enzyme-linked immunosorbent assay (ELISA). RESULTS: We found that the mean serum leptin levels in patients with ITP (22.11 +/- 15.84 ng/mL) were significantly (P < 0.001) higher than that in healthy control volunteers (5.44 +/- 4.84 ng/mL). Furthermore, serum leptin levels in patients with ITP were inversely related (r = -0.86, P < 0.001) to the platelet counts and positively related to the platelet-associated IgG (PAIgG) levels (r = 0.7, P < 0.001). The levels of PAIgG and platelet counts were significantly different between leptin-positive (level greater than mean +/- 2 SD control value) and leptin-negative patients. CONCLUSION: These findings suggest that leptin might play an important role in the pathogenesis of ITP.     

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.     

Idiopathic thrombocytopenic purpura in hodgkin's disease after splenectomy

This is a report of a patient with Hodgkin's disease who underwent a staging splenectomy and extensive radiation therapy and then developed “idiopathic” thrombocytopenic purpura. This appears to be the second known instance of such a combination of events. The patient was in complete remission of his Hodgkin's disease from radiation therapy at the time and continues in remission 56 mo since completing therapy. There was a complete and, apparently, permanent response of the thrombocytopenic purpura to a course of corticosteroid therapy.