Adult Immune Thrombocytopenic Purpura Patients Research Articles

PARTIAL SPLENIC EMBOLIZATION AS A TREATMENT FOR INTRACRANIAL HEMORRHAGE CAUSED BY IMMUNE THROMBOCYTOPENIC PURPURA

SESSION TITLE: Medical Student/Resident Critical Care Posters SESSION TYPE: Med Student/Res Case Rep Postr PRESENTED ON: October 18-21, 2020 INTRODUCTION: Immune Thrombocytopenic Purpura (ITP) is a disease of immune mediated platelet destruction and decreased production. Autoimmune platelet destruction occurs in tissue macrophages, mainly in the spleen. Initial treatment for ITP includes steroids and, for patients who require quicker elevation of platelet count, intravenous immunoglobulin (IVIG). Second line treatments include rituximab and newer agents that work by thrombopoiesis stimulation. Splenectomy, also a second line treatment, is generally used only after all medical options have failed due to potential complications. We report a case of partial splenic embolization (PSE) in a patient with refractory ITP presenting with acute intracranial hemorrhage (ICH). CASE PRESENTATION: A 38-year-old male with refractory ITP, initially treated with steroids, IVIG, and maintenance eltrombopag, presented to an academic medical center with two days of headache followed by acute onset weakness and slurred speech the day of presentation. Platelet count was 6k/uL; computed tomography (CT) found a pontine hemorrhage measuring 1.8x1.9x1.7cm causing effacement of the right ambient and pre-pontine cistern. He was initially treated with 4mcg/kg romiplostim, 60g IVIG, 40mg dexamethasone, 4U platelets and intubated for airway protection. Repeat laboratory results showed platelet count of 3k/uL; repeat CT showed expanding hemorrhage with worsening mass effect. Due to his worsening condition, we administered recombinant factor VIIa and performed an emergent PSE using approximately 3 ml of 300-500 µm embospheres via a right common femoral artery approach. Within nine hours of PSE, his platelet count increased to 218k/uL. Repeat CT showed stable hemorrhage; MRI did not show an underlying cause for his bleed. His platelets continued to increase, neurologic status improved and he was extubated. When the patient’s platelet count dropped to 79k/uL 11 days post-embolization, he underwent laparoscopic splenectomy. DISCUSSION: Splenectomy used to treat ITP has a high long-term remission rate.2 While there have been small, retrospective studies in the use of PSE with promising results, we found no reports in which PSE was used in an adult with ICH. Due to this presentation’s emergent nature, an active ICH and risk of bleeding, we opted for PSE rather than splenectomy for both speed and a presumed lower immediate complication rate. The PSE stabilized the patient by stopping the ICH and raising platelet count, enabling the patient to undergo laparoscopic splenectomy at a later date. CONCLUSIONS: PSE can be a safe alternative or bridge to splenectomy in patients with acute bleed due to ITP. Reference #1: Kuwana M, et al. Splenic macrophages maintain the anti-platelet autoimmune response via uptake of opsonized platelets in patients with immune thrombocytopenic purpura. J Thromb Haemost. 2009;7(2):322-329 Reference #2: Mikhael J, Northridge K, Lindquist K, Kessler C, Deuson R, Danese M. Short-term and long-term failure of laparoscopic splenectomy in adult immune thrombocytopenic purpura patients: a systematic review. Am J Hematol. 2009;84(11):743-748. DISCLOSURES: No relevant relationships by Lewis Eisen, source=Web Response No relevant relationships by Nader Emami, source=Web Response No relevant relationships by David Hirschl, source=Web Response No relevant relationships by David Schecter, source=Web Response

Clinical Presentation and Therapy of Primary Immune Thrombocytopenia Resistant to Splenectomy

Background: A satisfactory therapeutic response is achieved with splenectomy in 60–80% of the patients diagnosed with immune thrombocytopenic purpura (ITP). There is an ongoing consensus on the short-term efficacy of splenectomy, however, its long-term efficacy remains controversial. Our aim was to establish the frequency of resistance and relapse after splenectomy, the occurrence of complications, the therapeutic strategies and the drug efficacy in splenectomy-resistant ITP.
 Methods: We retrospectively analyzed 138 adult ITP patients who had been previously diagnosed and treated at the Clinic of Hematology, Clinical Center of Serbia, and who underwent splenectomy between 1987 and 2018.
 Results: Of the 138 ITP patients, 20.3% (n=28/138) were refractory to splenectomy, 11.6% (n=16/138) relapsed and 8.7% (n=12/138) were primarily resistant. The average post-splenectomy follow-up period was 117 months (range 3-474). The average follow-up period of the patients resistant to splenectomy was 147 months (range 23-474). Of the patients refractory to splenectomy, 67.8% (n=19/28) showed a good therapeutic response: 49% (n=14/28) complete remission and 18.8% (n=5/28) partial remission. The response was usually achieved using the following drugs: romiplostim (100%), eltrombopag (75%), cyclosporine (66.67%), mycophenolate mofetil (50%), danazol (50%) and corticosteroids (40.9%). Hemorrhagic and non-hemorrhagic complications occurred in 78.6% (n=22/28) and 28.6% (n=8/28) of the patients, respectively.
 Conclusion: Splenectomy remains a very efficient therapeutic modality for the treatment of ITP patients with a high percentage of splenectomy-resistant patients achieving remission. Thrombopoietin receptor agonists have shown exceptional results so far in the treatment of refractory ITP patients.

Prevalence of H. pylori in Immune Thrombocytopenic Purpura (ITP) in a tertiary care center, South India

Introduction: Immune thrombocytopenic purpura (ITP) has been linked with Helicobacter Pylori infection. Objectives: The objective of the present study was to determine the prevalence of H pylori infection in adult ITP patients in a tertiary care center in South India. Methods: 50 adult patients with ITP in the Department Hematology, Madras Medical College were recruited for a cross -sectional study over a period of 6 months. Biopsy from the antrum was subjected to Rapid urease test to detect H. pylori. A total of 50 patients participated in the study. Result: The prevalence of H. pylori infection in ITP patients was 36%. The majority of patients were male (78%). Conclusion: The diagnosis of H. pylori in ITP patients may be considered in high prevalent areas.

The impact of helicobacter pylori eradication on platelet counts of adult patients with idiopathic thrombocytopenic purpura

BackgroundIdiopathic (immune) thrombocytopenic purpura (ITP) is an acquired disorder characterized by autoantibodies against platelet membrane antigens. Several studies found an association between Helicobacter Pylori infection and the incidence of ITP. So far, It is still unclear whether H. pylori eradication will increase platelet counts in adult ITP patients. We conduct this study to investigate platelet recovery in ITP patients after H. pylori eradication.MethodsThis is a prospective study. The diagnostic criterion for Idiopathic thrombocytopenic purpura is: isolated thrombocytopenia, with no evidence of any underlying causes like drugs, TTP, SLE, hepatitis, HIV,CLL and… etc. We examined blood smears of all patients. We have diagnosed Helicobacter pylori infection by histological examination of several biopsies obtained from stomach and duodenum by esophagogastroduodenoscopy (EGD). If EGD was not applicable due to patient’s poor situation or platelet count, H.pylori infection was diagnosed by the positivity of serum antibodies or respiratory urease test. We treated infected patients with triple therapy (omeprazole 40 mg once daily, amoxicillin 1000 mg twice daily and clarithromycin 500 mg twice daily) for 14 days. Uninfected patients did not receive any treatment. We did platelet quantification at the beginning of the study, at the end of the first month, at the end of the third month and at the end of the sixth month.ResultsThis study involved 50 patients with chronic ITP, 29 males (58%) and 21 females (42%). Participants ages range between18 and 51 years (mean age = 28.60 years). We diagnosed H. pylori in 36 patients (72%), who were treated with triple therapy. At the end of the sixth month, 10 of them (27.77%) showed complete response, and 18 of them (50%) showed partial response. The 14 uninfected patients, who did not receive any treatment, did not show neither complete nor partial response. Patient sex and age were not associated with achieving response, while baseline platelet count and H.pylori infection did.ConclusionHelicobacter pylori eradication significantly increases platelet counts in adult ITP patients.

RhIL-11 treatment normalized Th1/Th2 and T-bet/GATA-3 imbalance in in human immune thrombocytopenic purpura (ITP)

Immune thrombocytopenia (ITP) is an autoimmune hemorrhagic disorder characterized by reduction in platelet counts. T helper 1 (Th1) cells polarization with an increased shift of Th1/Th2 ratio has been reported in ITP. This shift is associated with transcription factor T-box expressed in T cells (T-bet) upregulation and GATA-binding protein 3 (GATA-3) downregulation, leading to an increased T-bet/GATA-3 ratio. Our previous in vitro study showed that recombinant human interleukin-11 (rhIL-11) could normalize Th1/Th2 imbalance in the peripheral blood mononuclear cells (PBMCs) isolated from adult ITP patients, which co-occurred with T-bet/GATA-3 ratio restoration. In this report, we investigated whether rhIL-11 had therapeutic effect in clinical ITP patients and whether rhIL-11 treatment could normalize Th1/Th2 and T-bet/GATA-3 levels in vivo. We found rhIL-11 treatment had a response rate of 67.7% and significantly decreased Th1 and T-bet levels but increased Th2 and GATA-3 levels in ITP patients who showed good response, normalizing Th1/Th2 and T-bet/GATA-3 ratios similar to that in healthy controls. Thus our study suggested rhIL-11 was effective with tolerable adverse effects in ITP. The treatment strategy warrants further clinical investigation.

Downregulation of T-bet/GATA-3 ratio induced by IL-11 treatment is responsible for Th1/Th2 balance restoration in human immune thrombocytopenic purpura (ITP)

Abnormal cellular immunity induced by deranged Th1/Th2 profile has been revealed to play a critical role in the pathogenesis of immune thrombocytopenic purpura (ITP). Correction of the shifted Th1/Th2 balance represents a potential therapeutic approach to treat ITP. Here, we investigated the effects of IL-11 on the restoration of Th1/Th2 balance in the peripheral blood mononuclear cells (PBMCs) isolated from adult ITP patients. As shown here, we observed a higher ratio of T-bet/GATA-3 gene expression by quantitative real-time PCR in the PBMCs from ITP patients, consistent with the presence of an abnormally high Th1/Th2 ratio. Remarkably, upon IL-11 treatment, a reversal of T-bet/GATA-3 ratio in ITP was achieved and was shown to be responsible for the restoration of Th1/Th2 balance, with IL-11 at 100 ng/ml demonstrating the highest efficiency. T-bet and GATA-3 are the two transcriptional factors that have been indicated to be the master regulators for Th1 and Th2 lineage commitment, respectively. In the presence of 100 ng/ml IL-11, GATA-3 transcript abundance rose up to ~85-fold of that measured in untreated cells, whereas T-bet transcripts were lowered merely to ~41%, suggesting that GATA-3 was the major contributor for the reversal of T-bet/GATA-3 ratio. Thus, our findings may very well encourage the development of novel medicines that specifically target and correct the T-bet/GATA-3 imbalance identified in ITP.

Reviewed diagnosis of primary and secondary immune thrombocytopenic purpura in 79 adult patients hospitalized in 2000–2002

Despite the accepted distinction between primary and secondary immune thrombocytopenic purpura (ITP), a systematic analysis of the incidence of secondary ITP is not available. The present study was aimed at verifying the frequency and, consequently, the approximate rates of prevalence and incidence of secondary ITP and analysing its clinical and laboratory characteristics in patients needing ordinary hospital treatment for ITP. The study was based on 79 consecutive, adult ITP patients admitted to three Italian hospitals in 2000-2002. Using data collected in a previous study on the appropriateness of hospital management of ITP, we evaluated the frequency of secondary ITP, with the diagnosis formulated on the basis of new acquisitions, derived its rates of prevalence and incidence, and examined the available clinical and laboratory parameters. At our case review, a diagnosis of secondary ITP could be formulated in 38% of the 79 patients. This frequency was significantly higher than that determined at the time the patients were discharged from hospital (13.9%) (P = 0.000). The derived rates of prevalence and incidence of secondary ITP in the general population were, respectively, 2.3 and 1.23 per 100 000 inhabitants per year. In comparison with patients with primary ITP, those with a secondary form more frequently had spleen enlargement (P = 0.000), hepatomegaly (P = 0.001) and lower haemoglobin values (P = 0.005). The high frequency of secondary ITP must be mainly attributed to the currently available knowledge about the nature of some forms of ITP. Particular contributors to the high frequency were cases secondary to infections and those observed in patients who had undergone bone marrow or solid organ transplantation. Some clinical and laboratory alterations appear to be more frequent in secondary ITP than in primary ITP. However, the importance that the identification of particular forms of ITP, such as those secondary to Helicobacter pylori or hepatitis C virus infections, has on the choice of treatment suggests that these conditions must be ascertained independently of the presence or absence of clinical and laboratory alterations.

Appropriate hospital management of adult immune thrombocytopenic purpura patients in major Italian institutions in 2000–2002: a retrospective analysis

The treatment of immune thrombocytopenic purpura (ITP) still offers challenges to clinicians and health professional organizations, despite recommendations provided by international guidelines. In order to improve the care of patients with ITP, it is useful to understand how often such patients receive appropriate treatment and if common errors occur that could be avoided. We retrospectively analyzed all the clinical records between 1 January, 2000 and 31 December, 2002 of patients receiving an ICD-9-CM diagnosis code of 287.3 in three hospitals in northern Italy. We examined whether management strategies of adult men and nonpregnant women with ITP were consistent or not with the guidelines provided by the American Society of Hematology. The ITP diagnosis was confirmed in 120 of 169 patients (71%). Reasons for admission were: medical treatment for ITP (51.7%), medical or surgical treatment of ITP-associated disorders (30.8%), elective splenectomy (15.8%) and diagnosis or observation of ITP (1.7%). Hospital admission resulted appropriate in 78.1% of cases. Therapeutic interventions were appropriate in 100% of cases for glucocorticoid treatment, 86.4% for splenectomy, 47.7% for high-dose immunoglobulins, 40.9% for prophylaxis against bleeding before splenectomy, 33.3% for high-dose glucocorticoid treatment, and 19% for prophylaxis against bacterial infections before splenectomy. Platelet transfusions as treatment for bleeding were appropriate in only 20% of cases. Confirming the usefulness of the American guidelines for ITP, our data suggest that there are important areas of inappropriate management of the disease, which could be corrected by adopting quality improvement programs and studies.

Evaluation of Bleeding-Related Episodes in Patients with Chronic Immune Thrombocytopenic Purpura (ITP) Receiving Romiplostim or Medical Standard of Care.

Abstract 1311Poster Board I-334 BackgroundChronic ITP is an autoimmune disease characterized by low platelet counts and increased risk of bleeding that may be severe or even fatal. Rescue medications, most commonly intravenous immunoglobulins, are used to treat or prevent bleeding but produce only transient increases in platelet counts in most cases and may have issues with toxicity. Romiplostim is a peptibody protein designed to increase platelet production by binding to and activating the thrombopoietin receptor, and is approved for the treatment of adult chronic ITP. ObjectiveTo determine the effects of romiplostim treatment on bleeding outcomes during a phase 3b, randomized, open-label study, in adult nonsplenectomized ITP patients receiving either romiplostim or medical standard of care (SOC). We have developed a clinically-relevant composite endpoint, termed bleeding-related episode (BRE). A BRE was considered to be either an actual bleeding event, and/or the use of rescue medication to treat or prevent bleeding. MethodsPatients were randomized (2:1) to romiplostim or SOC. Eligible patients were required to have either a platelet count <50×109/L or have had their platelet count fall to <50×109/L during or after a clinically-indicated taper or discontinuation of current ITP therapy. Once-weekly subcutaneous romiplostim was administered with dose adjustments to target a platelet count between 50 and 200 × 109/L. SOC treatments were prescribed according to standard institutional practices or therapeutic guidelines. Since many types of ITP treatment could be administered in the SOC group, for the purpose of this analysis rescue medication was defined as any use of immunoglobulins (intravenous immunoglobulin or Anti-D), intravenous steroids, or platelet transfusions. In order to collapse related events into episodes, events (bleeding events and/or the use of rescue medication) that occurred concurrently or within 3 days of each other were considered a single clinical episode. Rates of BREs per 100 patient-weeks were calculated from the number of events/episodes divided by the number of patient-weeks on study treatment, multiplied by 100. ResultsDuring the 52-week treatment period, the total number of patient-weeks for the romiplostim group (N=154) was 7087, and for the SOC group (N=70) was 2571. During the treatment period, the rate of BREs was lower in the romiplostim group than the SOC group (see Table), with a 67% reduction in the rate of BREs in patients receiving romiplostim compared to SOC (95% CI, 60% to 73%). The rate of BREs involving the use of immunoglobulins was also lower in the romiplostim group, with a 95% reduction in the rate of BREs in patients receiving romiplostim compared to those receiving SOC (95% CI, 92% to 97%).TableRomiplostim N. of patients = 154 Patient-week=7087 r (n)SOC N. of patients = 70* Patient-week=2571 r (n)BREs3.1 (220)9.4 (241)BREs with immunoglobulins0.2 (17)4.8 (123)Events incorporated intoBREs**Bleeding3.7 (262)5.6 (144)Anti D0.0 (1)0.4 (9)IVIG0.3 (19)4.9 (127)IV steroids0.1 (8)0.4 (9)Transfusions0.3 (24)0.8 (20)Total4.4 (314)12.0 (309)Patient-week = Total patient weeks on study during treatment period, n = Number of events, r = duration-adjusted event rate per 100 patient-weeks ( n / Patient-week x 100)*5 of 75 patients randomized to SOC were excluded from this analysis due to use of rituximab at study entry**A single BRE could contain multiple events ConclusionsCompared to SOC, romiplostim was associated with a reduction in all BREs as well as BREs involving immunoglobulin use. DisclosuresStasi:Amgen Inc.: Honoraria, Speakers Bureau; GlaxoSmithKline: Honoraria, Speakers Bureau. Giagounidis:Amgen Inc.: Consultancy, Speakers Bureau. Janssens:Roche: Honoraria. Legg:Amgen Inc.: Employment, Equity Ownership. Danese:Amgen Inc.: Consultancy, Research Funding. Deuson:Amgen Inc.: Employment, Equity Ownership.

Short‐term and long‐term failure of laparoscopic splenectomy in adult immune thrombocytopenic purpura patients: A systematic review

Splenectomy is a common therapy for adults with chronic idiopathic thrombocytopenic purpura (ITP). Thisstudy was designed to estimate both the short-term surgical non-response rate and the long-term relapse rate after laparoscopic splenectomy. A systematic review was conducted of articles published between January 1, 1991 and January 1, 2008. Selection criteria included: chronic ITP, study enrollment in 1990 or later, > or =12 months of follow-up, > or =15 patients with ITP, > or =75% of patients at least 14 years of age, not HIV positive, not undergoing a second splenectomy, and type of performed splenectomy clearly reported. Data were pooled across studies to estimate rates. We identified 170 articles, of which 23 met our inclusion criteria (all observational studies). These studies represent 1,223 laparoscopic splenectomies (71 or 5.6% were converted to open splenectomy during surgery). The pooled short-term surgical non-response rate among the 18 studies reporting data was 8.2% (95% CI 5.4-11.0). The pooled long-term relapse rate across all 23 studies was 43.6 per 1,000 patient years (95% CI 28.2-67.2). This translates to an approximate failure rate of 28% at 5 years for all patients undergoing splenectomy. Studies with shorter durations of follow-up had significantly higher pooled relapse rates than studies with longer follow-up (P = 0.04). Laparoscopicsplenectomy is effective for most patients. Splenectomy may have higher initial relapse rates, particularly, in the first 2 years after surgery, and the rate may decline over time. Am. J. Hematol. 2009. (c) 2009 Wiley-Liss, Inc.

Low-Dose Humanized Anti-CD20 Monoclonal Antibody (MAb), Veltuzumab, in Adult Immune Thrombocytopenic Purpura (ITP): Initial Results of a Phase I/II Study.

BACKGROUND: Veltuzumab (hA20), a humanized MAb with significant structurefunction differences from rituximab, has shown clinical activity at low doses in non- Hodgkin's lymphoma. Since anti-CD20 immunotherapy has demonstrated activity in ITP with standard doses of rituximab, we hypothesized that low-dose veltuzumab would be effective in this disorder, thus also justifying subcutaneous injections. The goal of this first study in ITP is to evaluate the safety and tolerability of veltuzumab administered at low doses either intravenously or by subcutaneous injection, to obtain information on efficacy, pharmacodynamics, pharmacokinetics, and immunogenicity, and to determine feasible doses for further studies.METHODS: A multicenter, phase I/II study was initiated in adult ITP patients with platelets <30K/μL, and a prior history of platelets <150K/μL for >6 months, who had failed ≥1 standard therapy. Patients were administered 2 doses of veltuzumab 2 weeks apart and evaluated for efficacy over 12 weeks, with responding patients continuing evaluation in long-term follow-up. Efficacy was assessed by platelet level responses with increases confirmed at least 1 week apart classified as complete (CR, >150K/μL), partial (PR, 50–150K/μL), or minor (MR, 30–50K/μL) responses. Adverse events and safety laboratories were evaluated by NCI CTC v3 toxicity grades. Pharmacodynamics were evaluated by B-cell levels (CD19), while pharmacokinetics and immunogenicity were evaluated by serum veltuzumab levels and human anti-veltuzumab antibody (HAHA) titers, respectively, using an ELISA assay performed by the Sponsor.RESULTS: Seven patients (5F/2M, median age 41, 2 splenectomized) have now received intravenous veltuzumab at doses of 80 mg (N=3), 120 mg (N=3) or 200 mg (N=1). They had ITP for 0.5 – 12 years, had received prior steroids (N=7), IVIG and/or WinRho (N=6), or chemotherapy (N=3), and had 6–27 K platelets/μL and Grade 0–1 bleeding scores at study entry. One patient withdrew after receiving 100 mg and experiencing a Grade 3 infusion reaction, subsequently undergoing splenectomy. Otherwise, the treatment was well tolerated with all infusions completed within 60 – 90 minutes. Of the 6 evaluable patients, all 4 non-splenectomized patients responded to treatment with at least a doubling of their baseline platelet levels, achieving 2 CRs, 1 PR, and 1 MR. At present, both CRs are still continuing with >100 K platelets/μL at 16 and 24 weeks after treatment. The patient with a PR, who was treated at 80 mg, had platelets decreased <30K/μL at 11 weeks, but then achieved a second PR after retreatment at 120 mg, which is now ongoing 6 weeks later. The patient with MR still has platelets at least double the baseline levels at 12 weeks. Although neither of the 2 splenectomized patients responded, one had spontaneously increased platelets >30 K/μL just prior to 1st infusion and has continued to maintain these levels now 12 weeks after treatment, while the other has since been treated with cyclosporine, also without response. Veltuzumab quickly depleted B cells after the first dose, with decreases sustained >12 weeks. Even at these low doses, veltuzumab achieved expected serum levels (mean Cmax, 20.3 and 46.0 μg/mL at 80 and 120 mg, respectively) and remained in circulation without evidence of rapid clearance or sequestration (mean post-treatment half-life ~1 week). Two patients developed low-level positive HAHA results of uncertain clinical significance after treatment.CONCLUSIONS: These initial results indicate that doses of 80 or 120 mg veltuzumab have acceptable safety and demonstrate promising activity for ITP, including durable complete responses. Based on these findings, the study is proceeding, with patients now being recruited for therapy with low-dose veltuzumab administered by subcutaneous injection.

Treatment Patterns and Splenectomy Failure Rates in Patients with Chronic Immune Thrombocytopenic Purpura in Canada: A Retrospective Chart Review

Background: In clinical practice there is little consensus on treating patients with chronic immune thrombocytopenic purpura (ITP) beyond first line therapy with steroids.Objectives:Describe the demographic and disease characteristics of adult ITP patients who receive treatment;Obtain the treatment approach for patients with ITP beyond first line treatment with steroids, with an emphasis on splenectomy; andEvaluate adverse bleeding outcomes associated with ITP.Methods: A retrospective chart review of ITP patients after initial therapy with steroids was conducted. Ten physicians (oncologists and hematologists) were recruited from across Canada and each physician provided at least 5 ITP cases for review. A total of 51 cases were reviewed and patients (> 18 years old) were required to have had more than 1 course of steroids as treatment to be eligible.Results: The average age of patients at diagnosis was 42 (range 3 to 82 years); 37 (73%) of the patients were female, and 37 (73%) were Caucasian. The median platelet count upon presentation was 5×109/L. Median lines of therapy after initial therapy was 3 (range 0 to 6). Second line therapies varied, but most commonly patients underwent splenectomy (43%), followed by continued steroid treatment (16%), steroids plus IV Ig (16%), IV Ig alone (14%), immunosuppressant alone (2%), and anti-D plus steroids (2%). Of the patients reviewed, 40 (78%) eventually underwent splenectomy. Of the 40 splenectomized patients, 27 were splenectomized within the first year of diagnosis and 35 underwent splenectomy during the first 5 years. In addition, 62 of the splenectomies were laparoscopic, and the median hospital stay for all procedures was 5 days (range 1 to 60 days). Immediate failure of splenectomy occurred in 18% of patients, and the one- and five- year relapse/failure rates (defined as platelet count < 30×109/L) were 38% and 55%, respectively. Other therapies following splenectomy included IV Ig, azathioprine, cyclosporine, danazol, mycophenolate, rituximab, vincristine, cyclophosphamide, and anti-D. Only 6% of IV Ig use was for chronic maintenance therapy and 74% of use was for urgent therapy. A total of 61 bleeding events occurred, of which 10 were major (upper GI, mouth, rectal, and nose). Major bleeding events required hospitalization of the patient with an average length of stay of 5 days (range 2 to 14 days).Conclusions: Notwithstanding several limitations, the retrospective chart review suggests that there is wide variation in long-term therapy for patients with chronic ITP in Canada. Splenectomy was the most widely used second line therapy, although 18% of the patients were non-responders and the five-year relapse/failure rate was 55%.

Impact of chronic Immune Thrombocytopenic Purpura (ITP) on health-related quality of life: a conceptual model starting with the patient perspective.

BackgroundImmune thrombocytopenic purpura (ITP), a condition characterized by autoimmune-mediated platelet destruction and suboptimal platelet production, is associated with symptoms such as bruising, epistaxis, menorrhagia, mucosal bleeding from the gastrointestinal and urinary tracts and, rarely central nervous system bleeding. The aim of this research is to develop a conceptual model to describe the impact of ITP and its treatment on patients' health-related quality of life (HRQoL).MethodsA literature search and focus groups with adult ITP patients were conducted to identify areas of HRQoL affected by ITP. Published literature was reviewed to identify key HRQoL issues and existing questionnaires used to assess HRQoL. Focus group transcripts were reviewed, and common themes were extracted by grouping conceptual categories that described the impact on HRQoL.ResultsThe literature synthesis and themes from the focus group data suggest that decreased platelet counts, disease symptoms, and treatment side effects influence multiple domains of HRQoL for ITP patients. Key areas affected by ITP and its treatments include emotional and functional health, work life, social and leisure activities, and reproductive health.ConclusionITP affects various areas of HRQoL. This conceptual model will help inform the evaluation of therapeutic strategies for ITP.

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.

Health-Related Quality of Life (HRQoL) in Patients with Chronic Immune Thrombocytopenic Purpura (ITP): Interim Results from an Open-Label Study of AMG 531.

The ITP Patient Assessment Questionnaire (ITP-PAQ) was developed to complement clinical data by assessing multiple facets of disease-specific HRQoL in adult patients with chronic ITP (Mathias et al., Health Qual Life Outcomes, 2007). Here we present interim results from an ongoing, open-label extension study that will evaluate the ability of AMG 531 to improve their HRQoL in the long-term. AMG 531 is a novel thrombopoiesis-stimulating peptibody that is being studied for its ability to increase platelet production by stimulating the thrombopoietin receptor. Adult chronic ITP patients receiving AMG 531 completed the ITP- PAQ at baseline, and weeks 4, 12, 24, and every 12 weeks thereafter. The ITP-PAQ consists of 44 items and 10 scales. Data have been assessed for this interim analysis through week 48, a time-point with reasonable patient numbers at the time of the data cut-off. Mean scores at each assessment, and changes in mean scores from baseline to week 48 were calculated, with positive changes in mean score indicating improvement in HRQoL. Compliance rates for the ITP-PAQ were 95% at baseline, 93% at week 4, and 83% at week 48. Over the 48-week period, results demonstrated an upward trend for the scale scores (see Table). The greatest improvements were reported in the Symptoms, Bother, Activity, Reproductive Health, and Overall Quality of Life scales, particularly during the first 4 weeks of the study. Changes in mean score from baseline to week 48 were significantly increased for Symptoms, Bother, Fatigue, Activity, Fear, Psychological Health, Work, Social Activity, and Overall Quality of Life. ITP patients receiving AMG 531 had an initial, yet sustained, improvement in ITP-PAQ scores. Subsequent analyses of results collected in this ongoing study will be used to substantiate our findings, and the therapeutic benefit of AMG 531 on HRQoL in patients with chronic ITP will be provided by correlations with clinical data. [Display omitted]

Self‐reported health‐related quality of life in adults with chronic immune thrombocytopenic purpura

Adult chronic immune thrombocytopenic purpura (ITP) is a disorder manifested by varying degrees of purpura and mucosal bleeding, rarely including intracranial hemorrhage. Therapy is aimed at increasing the patient's platelet count to safe levels and includes a wide variety of treatments. While the diagnosis, treatment, and prognosis of chronic ITP have been extensively discussed, the effect of ITP and its treatment on patient quality of life has not been evaluated in adults. In this study, the Short-Form 36 questionnaire was used to evaluate the health-related quality of life (HRQOL) of 73 adult ITP patients compared with that of the general U.S. population and of patients with six other relatively common chronic disorders. This study shows that the HRQOL of adult patients with ITP is significantly worse than that of the general U.S. population. It is also worse than that of patients with hypertension, arthritis, or cancer; similar to that of patients with diabetes; but better than that of patients with congestive heart failure or a missing or paralyzed limb. Future studies need to address the effects of treatment not only on the platelet count and bleeding but also on HRQOL.

Response to Splenectomy Is Durable after a Certain Point in Time in Adult ITP Patients.

Background. Splenectomy is the recommended treatment in adult patients with immune thrombocytopenic purpura (ITP) who fail to respond to corticosteroid treatment or who require unacceptably high doses to maintain a safe platelet level. For these patients splenectomy may produce a good response in 60–80% of patients. However, the observation time after splenectomy has in most published studies been relatively short. Thus, the true long-term response to splenectomy still remains less well defined. The efficacy and safety of splenectomy were assessed in a cohort of adult ITP patients followed for a very long period of time.Patients and methods. The study included 59 ITP patients (M/F=25/34, median age at splenectomy; 39 yrs, range 14–75 yrs). The median time from diagnosis to splenectomy was 5.5 mos (range 0.4–199 mos). Criteria used to define response to splenectomy were: CR; platelet count >150 x 109/l lasting ≥4 weeks, PR; platelet count ≥50–150 x 109/l lasting ≥4 weeks and, NR; failure to achieve platelet counts ≥50 x 109/l. The criterion for relapse in CR/PR patients was a decrease in platelet counts to <50 x 109/l.Results. The median follow-up time after splenectomy was 18 yrs (range 2–32 yrs). No serious surgical complications occurred. The overall response rate was 78% with 59% CR and 19% PR. CR and PR patients were younger than NR patients at time of diagnosis (median age: 36 yrs vs 48 yrs, p=0.03) and at splenectomy (median age: 38 yrs vs 51 yrs, p=0.02). Among the 46 responding patients 17 eventually relapsed. A plateau in the progression free survival curve was identified after 12.1 and 7.3 years for patients in CR or PR, respectively. [Display omitted] At follow-up, 5 of 17 patients relapsing after splenectomy were in CR. Bacteremia was recorded in two patients during a total of 1023 patient years at risk.ConclusionsWe conclude that splenctomy is an effective and safe treatment in adult patients with chronic ITP failing to respond to corticosteroid treatment. The complication rate was low and our findings support the view that response to splenectomy is durable after a certain point in time.