Rituximab therapy for chonic and refractory immune thrombocytopenic purpura: a long-term follow-up analysis

The aim of this study was to evaluate the long-term response to rituximab in patients with chronic and refractory immune thrombocytopenic purpura (ITP). Adults with ITP fail to respond to conventional therapies in almost 30% of cases, developing a refractory disease. Rituximab has been successfully used in these patients. We used rituximab at 375 mg/m2, IV, weekly for a total of four doses in 18 adult patients. Complete remission (CR) was considered if the platelet count was >100 x 10(9)/l, partial remission (PR) if platelets were >50 x 10(9)/l, minimal response (MR) if the platelet count was >30 x 10(9)/l and <50 x 10(9)/l, and no response if platelet count remained unchanged. Response was classified as sustained (SR) when it was stable for a minimum of 6 months. Median age was 43.5 years (range, 17 to 70). Median platelet count at baseline was 12.5 x 10(9)/l (range, 3.0 to 26.3). CR was achieved in five patients (28%), PR in five (28%), MR in four (22%), and two patients were classified as therapeutic failures (11%). Two additional patients were lost to follow-up. The median time between rituximab therapy and response was 14 weeks (range, 4 to 32). SR was achieved in 12 patients (67%). There were no severe adverse events during rituximab therapy. During follow-up (median, 26 months; range, 12 to 59), no other immunosuppressive drugs were used. In conclusion, rituximab therapy is effective and safe in adult patients with chronic and refractory ITP. Overall response rate achieved is high, long term, and with no risk of adverse events.     

Laparoscopic splenectomies for idiopathic thrombocytopenic purpura: experience of sixty cases

We performed a laparoscopic splenectomy (LS) in 60 patients (age 9-83, 45 females) with idiopathic thrombocytopenic purpura (ITP) who did not achieve sustained remission on steroid therapy. Using a modified procedure, the mean duration of LS was 78 min (range 25-240 min) and surgery was associated with only 5% major and 5% minor complications. Ten patients had a platelet count less than 50 x 10(9)/l during surgery despite the administration of immune globulin (0.4 g/kg x 3-5 days) or pulsed oral dexamethasone (40 mg/day x 4 days). Three patients were refractory to these therapies and underwent LS with a platelet count less than 5 x 10(9)/l. Bleeding complications during or after surgery were rare (5%). Accessory spleens were removed in eight patients. Convalescence was rapid and the mean hospital stay was 2.3 days (range 1-7 days). The patients were followed for a mean of 16 months (range 1-36 months), and 49 patients (84%) are in complete remission. Seven patients (12.5%) relapsed despite an initial good response in 6 of them. Two patients underwent laparoscopic removal of accessory spleens with excellent response. We conclude that LS for ITP is safe and effective and associated with low morbidity and fast recovery. Thus, LS may be considered earlier in the course of ITP.     

Purification of Placenta-Eluted Gamma Globulins and Their Strong Effect against Graft-versus-Host Reactions In Vitro and In Vivo

A retrospective study was performed to determine the prevalence of Helicobacter pylori (H pylori) infection, the effect of H pylori eradication on platelet counts, and the characteristic clinical features of chronic immune or idiopathic thrombocytopenic purpura (ITP) with H pylori infection. H pylori infection was found in 300 patients, a group that was significantly older (P < .005) and had more cases of hyperplastic megakaryocytes in the bone marrow (P = .01) than patients without H pylori infection. H pylori eradication therapy was performed in 207 H pylori-positive ITP cases, and the platelet count response was observed in 63% of the successful eradication group and in 33% of the unsuccessful eradication group (P < .005). In the successful group, the complete remission and partial remission rates were 23% and 42%, respectively, 12 months after eradication. In the majority of responders, the platelet count response occurred 1 month after eradication therapy, and the increased platelet count continued without ITP treatment for more than 12 months. H pylori eradication therapy was effective even in refractory cases, which were unresponsive to splenectomy. In conclusion, H pylori infection was involved in most ITP patients older than 40 years in Japan, and eradication therapy should be the first line of treatment in H pylori-positive ITP patients.     

Splenectomy for refractory thrombocytopenia in the antiphospholipid syndrome.

OBJECTIVE: Thrombocytopenia, usually mild, is one of the clinical criteria of the antiphospholipid syndrome (APS). Rarely, this disorder requires treatment and, due to the shared characteristics with idiopathic thrombocytopenic purpura (ITP), similar rules are followed. We report our experience in patients who required splenectomy after being refractory to steroids and immunosuppressive therapy. METHODS: Fifty-five APS patients with a platelet count of < 100 x 10(9)/l at least twice were analysed retrospectively. Therapeutic response or remission was considered when the platelet count was > 100 x 10(9)/l after 1 month and with no relapse on stopping or tapering the steroid dose. No response or refractory disease was defined as an absence of increase in platelet count, a total count that never exceeded 50 x 10(9)/l during treatment or when the dose requirements were such that the patient developed serious side-effects. RESULTS: Fifty patients were classified as having secondary APS associated with systemic lupus erythematosus (SLE) and five were identified as primary APS (PAPS). Splenectomy was performed in 11 cases (20%), two PAPS and nine SLE-APS, with an average time of 28 +/- 9 months after the development of thrombocytopenia. Eight patients were initially characterized as ITP (six SLE-APS, two PAPS) with an average time of 4.4 +/- 1.1 yr until the APS diagnosis. All but two were responsive to splenectomy. CONCLUSION: Splenectomy was required in 11 (20%) of the patients with APS-associated thrombocytopenia. There was a high rate of good and long-term response.     

Clinicopathologic and prognostic features of chronic idiopathic thrombocytopenic purpura in adult Chinese patients: an analysis of 220 cases

To determine the clinicopathologic and prognostic features of chronic idiopathic thrombocytopenic purpura (ITP) in adult Chinese patients, we conducted a retrospective analysis of 220 patients seen at a single center over a 40-year period. The female-to-male ratio was 4:1, with a mean age of 42.1 +/- 1.3 years, a mean platelet count of 33.7 +/- 2.3x10(9)/l, and a mean follow-up of 116 +/- 7 months. Initial steroid treatment was required in 142 patients, 67 of whom (47.2%) achieved complete remission (CR). At 470 months, 46% patients remained in CR. Splenectomy was performed in 37 patients: in 23 patients due to primary steroid refractoriness and in 7 patients due to disease relapse following initial CR with steroids. In seven patients, data on response to steroids prior to splenectomy were not available. Splenectomy for steroid nonresponders resulted in an inferior CR rate (13 of 23, 56%) as compared with that for relapses after steroid treatment (7 of 7, 100%) (P<0.05). Compared with patients with negative antinuclear antibody (ANA), those who were ANA positive had similar responses to steroids, but significantly shorter remission after splenectomy (P<0.01). In conclusion, Chinese patients with ITP could maintain long-term remission after steroid therapy and splenectomy. In addition, primary steroid refractoriness and positive ANA were bad prognostic factors of the subsequent response to splenectomy.     

Durability and factors associated with long term response after splenectomy for primary immune thrombocytopenia (ITP) and outcome of relapsed or refractory patients

Splenectomy is the usual form of therapy for immune thrombocytopena (ITP) after steroid failure. We retrospectively studied the data in adult patients who underwent splenectomy for ITP from July 1996 to June 2008 to evaluate the long term responses, clinical and laboratory factors associated with long term responses and outcome of relapsed or refractory patients. Thirty eight patients, 30 (79%) females, with a median age of 23 years (range 15-69), underwent splenectomy. The procedure was laparoscopic in 28 (73.5%) and open in 10 patients. Splenectomy resulted in a response in 34/38 (89.5%) patients and failed in four (10.5%) patients. After a median follow-up of 58 months (range 7-144), 24 (63%) patients had a maintained response without treatment (platelet count of >50 × 10?)/l). Most of the relapses occurred during the first year but two patients had late relapses. There were procedure-related complications in seven (18.0%) patients but no cases of overwhelming sepsis. Only four relapsed or refractory patients had a platelet count below 50 × 10?/l at the last follow-up indicating response to alternative therapies. Responsiveness to steroids before the procedure (p = 0.025) along with a platelet count of ≥ 150 × 10?/l at 4 weeks (p =?< 0.0001) and a highest platelet count of ≥ 400 × 10?/l at any time post-splenectomy (p = 0.005), were associated with a long term response in univariate analysis. In conclusion, splenectomy remains an effective treatment for ITP after steroid failure in terms of long term responses, and the majority of relapsed or refractory patients respond to alternative therapies.     

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.     

Efficacy and safety of dapsone as a second-line treatment in non-splenectomized adults with immune thrombocytopenic purpura

In adults with immune thrombocytopenic purpura (ITP), steroids are usually proposed as first-line therapy, but long-term complete responses are obtained in no more than 20% of patients. For the remaining patients, splenectomy is considered the treatment of choice, with reported "cure" rates from 60-70%. However, the inherent risks of surgery and sepsis after splenectomy without a guarantee of success justify the search for strategies aimed to avoid splenectomy. Here we retrospectively evaluated the results of dapsone treatment in ITP patients that failed first-line therapy with steroids. These patients received dapsone 100 mg/day for a minimum of 30 days before splenectomy was considered. Efficacy was defined as a sustained rise in platelet counts (>50 x 10(9)/l) clearly attributed to dapsone treatment. Among 52 steroid-dependent or refractory patients, dapsone resulted in sustained increases in platelet counts in 44.2% of patients, after a median follow-up of 21.10 months after treatment initiation. The long-term efficacy of dapsone in this setting is further corroborated by the observation that none of the "responding" patients required splenectomy in the follow-up, compared to 69.0% of the "non-responding" patients. Dapsone-related adverse events were mild and promptly reversed by treatment withdrawal. The results of our retrospective analysis suggest that dapsone is a safe and effective second-line agent for steroid-dependent or refractory ITP patients. Because of its well-known safety profile and low cost compared to other potential second-line treatments for ITP, a trial course of dapsone should be viewed as an attractive option before splenectomy in steroid-dependent of refractory adult ITP patients.     

Intravenous gammaglobulin (Gaminume) for treatment of chronic idiopathic thrombocytopenic purpura (ITP): a two-year follow-up

Thirteen subjects 5-20 years of age with the chronic, autoimmune form of idiopathic thrombocytopenic purpura (ITP) were given intravenous gammaglobulin (Gamimune; Cutter Biological, Berkeley, CA) in a dose of 400 mg/kg per day for 5 consecutive days. Two of the 13 children had undergone splenectomy; the other 11 had not. Eight of these 13 children had also received corticosteroid therapy with no sustained increase in platelet counts. Six of 13 children had a good or excellent response to the first 5 day course of gammaglobulin therapy, and one had a fair response. The peak platelet count occurred within 7 days of the start of therapy except in one patient, whose platelet count peaked on day 12. Six of seven patients who initially responded to Gamimune required booster doses to maintain platelet counts at a safe level. All children had marked increases in serum IgG following Gamimune except one (who had undergone splenectomy for chronic ITP), who had high baseline levels of immunoglobulin G (IgG). No untoward reactions necessitating cessation of therapy were encountered during this study. The most common side effect observed was headache. During the first year of follow-up after Gamimune, three of seven initial responders became refractory to Gamimune therapy. Two of these three refractory subjects later underwent splenectomy with excellent response. The third refractory patient who was splenectomized prior to gammaglobulin therapy had spontaneous remission of his ITP 5 months after the last dose of Gamimune. Three of the four other initial responders have continued to do well and have maintained platelet counts above 40,000/mm3 (one without booster). The fourth subject dropped out of the study. Thus our observations indicate that Gamimune is an effective form of treatment for some children with chronic ITP, and can be considered as an alternative to splenectomy or as a potential therapeutic modality in those who have failed to respond to splenectomy.     

Long term follow-up after splenectomy performed for immune thrombocytopenic purpura (ITP)

Splenectomy is the only treatment of ITP known to have "curative" effects in a substantial fraction of patients. However, the true long-term outcome is uncertain and controversial because published series have not adjusted for the duration of follow-up. This IRB-approved retrospective study included all patients with ITP who underwent splenectomy between 1988-1993 at three major medical centers and required a minimum postoperative 5-year follow-up. Complete response (CR) was defined as all postsplenectomy platelet counts >150 x 10(9)/L without treatment; partial response (PR) as platelet counts > or =50 x 10(9)/L without treatment; and failure as platelet counts <50 x 10(9)/L or receiving therapy after splenectomy. Seventy-five patients identified with ITP underwent splenectomy from 1988 to 1993. Three patients died prior to 5-year follow-up, and 56 of the 72 patients (78%) were evaluable with follow-up for five years or longer, median 7.5 years. The immediate postoperative complete remission rate was 77%; 57% of patients have remained in prolonged CR. Thirty-seven patients (66%) have not required any therapy after splenectomy. Eight patients had platelet counts >150 x 10(9)/L for 4-8.5 years before relapsing; no clear plateau was attained in the remission curve. There was no operative mortality. Ten patients (18%) reported minor postoperative bleeding episodes. No life-threatening infections, significant heart disease, or pulmonary hypertension developed after splenectomy in the 434 patient-years of follow-up. This study helps to define the long-term results of splenectomy for ITP.     

Intravenous gammaglobulin treatment of chronic idiopathic thrombocytopenic purpura

High-dose intravenous gammaglobulin (IVIgG) was given to 12 children and adults with chronic idiopathic thrombocytopenic purpura (ITP) to avoid splenectomy or because they either failed to respond to or required maintenance with high doses of steroids and/or immunosuppressives. The average platelet count increase to initial therapy was 239,500/microliters (range 23,000-790,000). A concomitant IgG Fc receptor blockade, measured by IgG-sensitized 51Cr-labeled autologous erythrocytes, was seen in 11 of 11 patients tested, both splenectomized and not splenectomized, lasting 3-4 wk. Six or more months after treatment, 2 children are in remission, 2 children and 2 adults are stable requiring no therapy with platelet counts of approximately 50,000 and 30,000, respectively, 3 children require maintenance IVIgG therapy at 2-10-wk intervals, and 1 child and 2 adults have become refractory to further IVIgG. Splenectomy was not performed in 4 children. Two adults were able to discontinue daily prednisone. The 3 patients who became unresponsive to Swiss Red Cross gamma-globulin (IgSRK) therapy did so in conjunction with a markedly elevated platelet-associated IgG and IgM. Serum IgM increased an average of 103 mg/dl after the IVIgG infusions. No significant side effects were seen.     

Efficacy and safety of dapsone as a second-line treatment in non-splenectomized adults with immune thrombocytopenic purpura

In adults with immune thrombocytopenic purpura (ITP), steroids are usually proposed as first-line therapy, but long-term complete responses are obtained in no more than 20% of patients. For the remaining patients, splenectomy is considered the treatment of choice, with reported “cure” rates from 60–70%. However, the inherent risks of surgery and sepsis after splenectomy without a guarantee of success justify the search for strategies aimed to avoid splenectomy. Here we retrospectively evaluated the results of dapsone treatment in ITP patients that failed first-line therapy with steroids. These patients received dapsone 100 mg/day for a minimum of 30 days before splenectomy was considered. Efficacy was defined as a sustained rise in platelet counts (>50 × 10⁹/l) clearly attributed to dapsone treatment. Among 52 steroid-dependent or refractory patients, dapsone resulted in sustained increases in platelet counts in 44.2% of patients, after a median follow-up of 21.10 months after treatment initiation. The long-term efficacy of dapsone in this setting is further corroborated by the observation that none of the “responding” patients required splenectomy in the follow-up, compared to 69.0% of the “non-responding” patients. Dapsone-related adverse events were mild and promptly reversed by treatment withdrawal. The results of our retrospective analysis suggest that dapsone is a safe and effective second-line agent for steroid-dependent or refractory ITP patients. Because of its well-known safety profile and low cost compared to other potential second-line treatments for ITP, a trial course of dapsone should be viewed as an attractive option before splenectomy in steroid-dependent of refractory adult ITP patients.     

New therapeutic options for adult chronic immune thrombocytopenic purpura: a brief review

BACKGROUND: Patients with chronic immune thrombocytopenic purpura (ITP) only require treatment if they are bleeding, or prior to scheduled operations. Patients are also treated if platelet counts are very low. Some patients become refractory, relapse or do not respond to treatment with steroids. Splenectomy is effective in raising the platelet count in most patients, but as spontaneous remission may occur even after 1 year or more, it is justified to defer splenectomy. Furthermore, splenectomy and/or first-line treatment modalities may not suit all patients. Therefore, alternatives are desirable. MATERIALS: This review will focus on anti-B cell therapy with rituximab, and two thrombopoietin mimetic agents that have entered clinical trials, AMG 531 and eltrombopag. These therapeutics have been studied in patients who were refractory to first-line treatment and/or splenectomy, and to defer splenectomy. RESULTS: There are no controlled trials with rituximab, but clinical experience has shown a success rate of 40% to 60%. Encouraging phase 1 and 2 data have been published for both thrombopoietin mimetics; preliminary data from an open-label extension trial with AMG 531 and from phase 3 studies with eltrombopag further confirm their efficacy. CONCLUSION: Clinical experience will ultimately determine the appropriate indications of these new treatments for ITP.     

Danazol therapy in patients with chronic idiopathic thrombocytopenic purpura: long-term results

BACKGROUND: Adults with chronic idiopathic thrombocytopenic purpura (ITP) in whom standard-dose corticosteroids and splenectomy have failed or who have contraindications to these therapies often require further treatment for life-threatening thrombocytopenia or bleeding. We studied whether danazol, an attenuated androgen, is useful in this setting. METHODS: To assess both clinical outcome and tolerance issues, 57 patients who had refractory chronic ITP (n = 27) or who had contraindications to splenectomy or corticosteroids or who refused these therapeutic options (n = 30) were studied. RESULTS: Thirty-eight patients experienced a partial or complete response to therapy (67%), among whom 27 (46%) remained in remission at a median (+/- SD) of 119 +/- 45 months. Treatment tolerance was acceptable, although severe adverse events were reported in 9 patients (16%). CONCLUSION: Our findings suggest that danazol therapy may be beneficial in the management of refractory chronic ITP or when there are contraindications to splenectomy or corticosteroids (or both).     

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.     

Effects of prednisone and splenectomy in patients with idiopathic thrombocytopenic purpura: only splenectomy induces a complete remission

Idiopathic thrombocytopenic purpura (ITP) is a heterogeneous disease, whereby it is unclear if and in which way prednisone and splenectomy affect the platelet kinetics leading to a complete remission. To determine the effects of prednisone and splenectomy on the mean platelet life (MPL) and platelet production, platelet kinetic studies with Indium-111 tropolonate-labeled autologous platelets were performed in patients with ITP ( n=41). In 17 patients platelet kinetic studies were performed before and during prednisone treatment, and in 24 patients before and after splenectomy. MPL increased after prednisone therapy only in patients ( n=13) with a full recovery (FR, platelets >150 x 10(9)/l) and partial recovery (PR, 50 x 10(9)/l 相似文献   

Isolated thrombocytopenia in patients infected with HIV: treatment with intravenous gammaglobulin

Isolated thrombocytopenia occurs frequently in patients infected with HIV. Studies of mechanisms of thrombocytopenia and clinical response to therapy suggest that the thrombocytopenia is often antibody mediated (ITP). The best approach to treatment of these patients is uncertain in that the routine modalities (steroids, splenectomy, vinca alkaloids) that are used to increase the platelet count in patients with classic ITP are known to be immunosuppressive. We report here the results of intravenous gammaglobulin (IVGG) treatment of 22 patients with HIV-related acute and chronic ITP who had severe thrombocytopenia and bleeding symptoms. Only one patient had an opportunistic infection at the time of treatment. Eight patients were homosexual, eight had hemophilia, three were i.v. drug abusers, two children had congenital acquisition of HIV, and one was the wife of an HIV + i.v. drug abuser. The average pretreatment platelet count was 22,000/microliter (hemophiliacs were treated at higher platelet counts than were the other patients), and the mean peak platelet count measured on days 5 to 8 was 182,000/microliter. Nineteen of 22 patients had peak platelet counts greater than 50,000/microliter following IVGG and 17/22 had peak counts greater than 100,000/microliter. After the initial infusions, all but three refractory patients could maintain adequate platelet counts with IVGG alone infused no more often than once every 2 weeks. The outcomes for the 22 patients after multiple maintenance IVGG infusions were remission, 5; stable without therapy, 1; maintenance, 13; and refractory, 3. The eight hemophiliacs with ITP responded better than did the eight homosexual ITP patients; their mean peak platelet count was 227,000/microliter versus 142,000/microliter in the homosexuals. In summary, patients with HIV-related ITP without opportunistic infections responded well to IVGG, with peak platelet counts comparable to those of ITP patients not infected with HIV. IVGG may be a useful therapy of ITP in HIV+ patients, since it appears to be less immunosuppressive than are conventional therapies, and none of the 22 HIV+ patients developed an opportunistic infection while receiving IVGG alone.     

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.     

Bacterial infection-associated improvement of platelet counts in two patients with chronic and unresponsive idiopathic thrombocytopenic purpura with normal platelet survival studies

Summary. Approximately 20% of adult patients with idiopathic thrombocytopenic purpura (FTP) do not respond to splenectomy and require alternative therapies to achieve a clinically safe platelet count. A small percentage of these patients have very refractory disease and are either unresponsive or poorly responsive to almost any therapy. In this report we describe two patients with chronic and unresponsive ITP with normal platelet survivals. Neither patient had responded to a large variety of treatments including corticosteroids, splenectomy, IVIgG, anti-D, chemotherapy, and ascorbic acid. However, both had a rapid, but short-lived, rise in their platelet count following a bacterial infection. One patient had a rise in platelet count for 6 months following the acute episode of bacteraemia. The second patient had a shorter response of 1 week. It is possible that these two patients represent a subset of patients with ITP who may benefit from cytokine therapy.     

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.