Symptomatic Immune Thrombocytopenia Research Articles

Comparison of Response to Rituximab Therapy in Adults with Refractory Symptomatic Immune Thrombocytopenia According to the Presence of Accessory Spleen.

No data exist for the association between the presence of accessory spleen after splenectomy and response to rituximab in immune thrombocytopenia (ITP). We investigated the relationship between accessory spleen presence and rituximab response in splenectomized ITP patients. Fifteen chronic refractory ITP patients were included. Four weekly doses of rituximab 375 mg/m2 were administered. All patients had undergone splenectomy before rituximab administration. Accessory spleen was detected in 5 of 15 patients (33.3%). Median age at diagnosis was significantly higher in patients with accessory spleen than those without accessory spleen (40 (range 25–68 years) and 26 (range 7–40 years), respectively; p = 0.049). There was a trend for older age at time of rituximab initiation in patients with accessory spleen compared to the other group (median 51 (range 43–75 years) and 42.5 (range 30–60 years), respectively; p = 0.066). Median follow-up duration was 96 months (range 40–98). We demonstrated a significant correlation between accessory spleen presence and older age. Accessory spleen presence correlated with higher platelet and WBC counts. We showed good inverse correlation between presence of accessory spleen and time to early response (ER) to rituximab while the rate of early response (ER), late response (LR), sustained response (SR) and overall response (OR) did not differ with respect to the presence of acessory spleen.

COVID-19-associated severe immune thrombocytopenia

The novel coronavirus disease (COVID-19) is not only a disease that affects the respiratory system but also a systemic disease resulting in various symptoms and complications. Haematological changes are common in patients with COVID-19 but reports of severe immune thrombocytopenia (IT) in patients with COVID-19 are rare. Hereby a case is presented of a 72-year-old male patient who developed severe, symptomatic IT a month after COVID-19. Thereinafter, aetiology, pathophysiology, diagnosis as well as treatment options were widely discussed.

Use of thrombopoietin receptor agonists for immune thrombocytopenia in pregnancy: results from a multicenter study

AbstractManagement of immune thrombocytopenia (ITP) during pregnancy can be challenging because treatment choices are limited. Thrombopoietin receptor agonists (Tpo-RAs), which likely cross the placenta, are not recommended during pregnancy. To better assess the safety and efficacy of off-label use of Tpo-RAs during pregnancy, a multicenter observational and retrospective study was conducted. Results from 15 pregnant women with ITP (pregnancies, n = 17; neonates, n = 18) treated with either eltrombopag (n = 8) or romiplostim (n = 7) during pregnancy, including 2 patients with secondary ITP, were analyzed. Median time of Tpo-RA exposure during pregnancy was 4.4 weeks (range, 1-39 weeks); the indication for starting Tpo-RAs was preparation for delivery in 10 (58%) of 17 pregnancies, whereas 4 had chronic refractory symptomatic ITP and 3 were receiving eltrombopag when pregnancy started. Regarding safety, neither thromboembolic events among mothers nor Tpo-RA–related fetal or neonatal complications were observed, except for 1 case of neonatal thrombocytosis. Response to Tpo-RAs was achieved in 77% of cases, mostly in combination with concomitant ITP therapy (70% of responders). On the basis of these preliminary findings, temporary off-label use of Tpo-RAs for severe and/or refractory ITP during pregnancy seems safe for both mother and neonate and is likely to be helpful, especially before delivery.

Management of Adult Patients with Primary Immune Thrombocytopenia (ITP) in Clinical Practice: A Consensus Approach of the Spanish ITP Expert Group.

Background and Objective Diagnosis and management of primary immune thrombocytopenia (ITP) have changed dramatically in the last decade. The aim of the study was to obtain information about the opinion of the Spanish ITP Group (GEPTI) members regarding the best clinical practices for diagnosis and management of adult patients with ITP. Materials and Methods A two-round Delphi method was carried out by sending to 129 experts a 90-item questionnaire developed by 11 specialists, with a 4-point Likert scale (“never,” “sometimes,” “frequently,” and “always”) for the assessment of responses. Results Forty out of the 129 experts participated in the survey (participation rate 30.2%) and 39 completed the questionnaire (response rate 97.5%). Salient consensus points included the following: the need to indicate workup studies from a sustained platelet count < 100 x 109/L in the absence of a clear etiology; bone marrow aspiration in elderly patients with suspected ITP; beginning treatment in asymptomatic patients with a platelet count < 20 x 109/L; not exceeding 6-7 weeks of corticosteroid therapy; switching from corticosteroids to one thrombopoietin receptor agonist (TRA); switching to other TRA or other options as combinations of them with immunosuppressive drugs in case of failure; how to reduce tapering TRA; treating patients with symptomatic persistent ITP and platelet count > 20 x 109/L; and considering mucosal or severe bleeding as a basic criterion for hospital admission. Conclusions The present consensus document provides a reference framework for the management of patients with ITP in clinical practice.

Trends of Splenectomy in Pediatric Patients with Immune Thrombocytopenia before and after the ASH 2011 Evidence-Based Practice Guidelines

Background: Immune thrombocytopenia (ITP) is an autoimmune disorder which affects 1 in 10,000 children. Thrombocytopenia occurs largely due to rapid destruction of antibody sensitized platelets in the reticuloendothelial system. While spontaneous resolution is commonly seen in acute ITP, treatment of chronic or persistent ITP is controversial and could pose as management challenges for clinicians. Splenectomy increases platelet survival by removing a common site of platelet destruction and has a 70-80% response rate, however, published literature is conflicting regarding its ideal timing. Furthermore, it is an invasive procedure with significant risk of infections, venous thromboembolism. In 2011, the American Society of Hematology (ASH) published revised clinical practice guidelines for the management of ITP (Neunert C et al. Blood 2011). Splenectomy was recommended in patients with severe symptomatic ITP with significant or persistent bleeding refractory to intravenous immunoglobulin (IVIG), corticosteroids, and anti-D therapy. It is unclear if the rates of splenectomy have changed since the publication of these guidelines. Using a large population-based estimate, we aimed to study the trends of splenectomy in pediatric patients with ITP, and the factors predicting the procedure in this population.Methods: We used discharge data from the National (Nationwide) Inpatient Sample (NIS), Healthcare Cost and Utilization Project (HCUP), Agency for Healthcare Research and Quality (AHRQ). Pediatric patients (age ≤ 18 years) hospitalized with ITP from 2005-2014 were identified using International Classification of Diseases, Ninth Revision, Clinical Modification (ICD9-CM) code 287.31. Cases of total splenectomy were identified using ICD9-CM procedure code ‘41.50‘. To calculate estimated trends of splenectomy, Cochran-Armitage trend test was used. Chi-square test, Mann-Whitney U test, survey logistic regression and hierarchal regression were used for analyses. Weights provided by NIS were used to calculate national estimates. A p-value < 0.05 was considered significant. All analyses were performed using SAS 9.4 (SAS Institute Inc., Cary, NC, USA).Results: The NIS data included 62 million weighted pediatric hospitalizations between 2005 and 2014 (unweighted admissions n=13 million). After excluding patient transfers, a total of 40,998 weighted hospitalizations with ITP occurred during this time-period. Total splenectomy was performed in 1,009 patients. Splenectomy rate showed a decline prior to revised guidelines: 3.3% (2005-06) to 2.3% (2011-12). It continued to decline further after the publication: 1.6% (2013-14), p <0.0001. Similar trend was noted for patients < 5 years of age: 10.6% (2005-06), 5.2% (2011-12), and 3.5% (2013-14), p <0.001. None of the other patient ages (5-10, 11-15, and 16-18), gender, or hospital regions showed consistent splenectomy trend in either direction. Multivariable analysis showed one year increase in patient age significantly increased adjusted odds of having splenectomy (odds ratio, OR 1.18, 95% confidence interval, CI 1.14-1.22, p <0.0001). Having an intracranial bleed also significantly predicted splenectomy (OR 5.16, 95% CI 1.96- 13.61, p=0.0009). Splenectomy was more commonly done in patients from Midwest (OR 2.83, 95% CI 1.19-6.74, p= 0.02) and South region (OR 1.89, 95% CI 1.02-3.51, p=0.04) compared to Northeast region. Mortality rate was similar between patients who received splenectomy and who did not.Conclusion: Overall, splenectomy rates showed consistently downward trend in pediatric patients with ITP between 2005 and 2014. Reduction in splenectomy rates in children <5 years of age could be due to increasing awareness for sepsis secondary to asplenia. Presence of severe bleeding (e.g. intracranial bleeding) in patients with ITP predicted splenectomy, which is consistent with ASH recommendations. Declining splenectomy rates in last 3 years since ASH guidelines release could mean that more patients receive medical management initially as recommended by ASH. However, due to possible under-coding for IVIG, corticosteroids, and anti-D and lack of longitudinal data, we were unable to study the association between prior treatment and splenectomy. Future studies should revisit the role of splenectomy in ITP with advent of novel therapeutic options such as thrombopoietin receptor agonists. DisclosuresNo relevant conflicts of interest to declare.

Rituximab Therapy in Adults with Refractory Symptomatic Immune Thrombocytopenia: Long-Term Follow-Up of 15 Cases.

Objective:This paper prospectively evaluates the long-term follow-up [mean ± standard deviation (SD) duration: 89.7±19.4 months] data of 15 patients (13 females and 2 males) with refractory symptomatic immune thrombocytopenia (ITP) treated with rituximab.Materials and Methods:Rituximab was administered at 375 mg/m2 weekly for a total of 4 doses. Complete response (CR) was defined as a platelet count of ≥100,000/mm3 and partial response (PR) as a platelet count of ≥30,000/mm3 but less than 100,000/mm3. Early response (ER) and late response (LR) were defined as response within 42 days and after 42 days of initiation of rituximab therapy, respectively. Sustained response (SR) was defined as response lasting for at least 6 months.Results:Mean age (±SD) at the start of rituximab was 46.6±11.3 years. Mean platelet count (±SD) prior to rituximab treatment was 17,400±8878/mm3. The mean time (±SD) between rituximab therapy and response to rituximab in early responders and late responders was 1.8±1.3 weeks and 10±2.8 weeks, respectively. Mean durations (±SD) of ER and LR were 51±47.2 months and 6±4.2 months, respectively. Seven of the 15 patients (46.7%) showed an initial response to rituximab (5 ER and 2 LR). The rate of SR over 6 months was 26.7% (4/15). Among the responders to rituximab, 3 (3/7, 42.9%) maintained their response 1 year after rituximab treatment and 2 (2/7, 28.6%) had ongoing response 5 years after initiation of rituximab. Two of the 7 patients (28.6%) still maintained their response 98 months after initiation of rituximab. All 5 initial responders with subsequent relapse achieved response from subsequent treatment modalities (3 CR, 2 PR).Conclusion:Our data confirm, over a long period of observation, that rituximab is safe and effective in the management of patients with chronic refractory primary ITP.

Diagnosis and management of immune thrombocytopenia in childhood.

Evidence-based medicine is growing in immune thrombocytopenia (ITP), but solid clinical data are still lacking in many areas. A majority of children has self-limited ITP, but chronic symptomatic ITP exists also in pediatrics. Management includes a watch-and-wait strategy for children with newly diagnosed ITP and no or mild bleeding, and immunoglobulins and corticosteroids, if more bleeding and mucous membrane involvement is present. Treatment endpoints differ in clinical research and in clinical practice. The requirement of platelet enhancing drugs needs to be better defined in guidelines. Second-line therapies for children are rarely required and include thrombopoietin-receptor agonists, rituximab, dexamethasone and immunosuppressants. Thrombopoietin-receptor agonists are successful in adult but also in pediatric ITP. The strategical position of splenectomy differs from that in adults. Although effective in children it is less frequently used because of its life-long cumulative risk of infectious diseases and a higher potential of spontaneous remission in ITP, providing a strong argument to defer splenectomy. The rarity of ITP makes clinical research expensive.

Effect of Romiplostim on Health-Related Quality of Life in Children with Immune Thrombocytopenia and Associated Burden in Their Parents: Results from a Phase 3, Randomized, Double-Blind, Placebo-Controlled Study

▪Background: Immune thrombocytopenia (ITP) is an autoimmune disorder characterized by low platelet count levels and increased risk of bleeding. Symptomatic ITP in children can have a negative impact on their health-related quality of life (HRQoL) and increase their parents' burden. The effect of romiplostim (a thrombopoietin receptor agonist) on HRQoL and parental burden was evaluated in a phase 3 study of children with ITP.Methods: In a phase 3, randomized, double-blind, placebo-controlled study on efficacy and safety of romiplostim, children (<18 years) with ITP ≥ 6 months were randomized to weekly romiplostim or placebo for 24 weeks. The Kids' ITP Tool (KIT), a psychometrically-valid disease-specific HRQoL instrument (Klaassen Ped Blood Cancer2007), was administered to children and/or their parents at baseline, weeks 8, 16, and 25. All three KIT versions were used: Child self-report (to assess HRQoL of children ≥7 years), Parent/Proxy (to assess HRQoL of children <7 years via parent proxy), and Parent self-report (to assess impact of children's ITP on parental burden, for children of all ages). Each KIT version contains 26 items, summarized in a single score ranging from 0 to 100. Higher Child or Parent/Proxy KIT scores reflect better HRQoL of a child with ITP, and higher Parent KIT scores reflect less parental burden.Among efficacy endpoints of the study, overall platelet response was defined as achieving a weekly platelet response (platelet count ≥ 50 x 109/L) for ≥ 4 weeks during weeks 2 to 25, and durable platelet response was defined as achieving a weekly platelet response for ≥ 6 weeks during weeks 18 through 25.As exploratory endpoints of the study, changes in KIT scores from baseline to each follow-up assessment were estimated separately by treatment group (romiplostim or placebo) and by overall/durable platelet response status (yes/no). A mixed effects repeated measures analysis was conducted to estimate the difference in changes of Child and Parent KIT scores between romiplostim group and placebo group, controlling for baseline score, child's age, child's gender, and child's race (analysis of Parent/Proxy data was not conducted due to small sample size).Results: Sixty-two patients were enrolled and randomized to receive romiplostim (42 patients) and placebo (20 patients). Mean age was 9.6 years (range: 3-17, 16 patients <7 years), 57% were female, and 66% were white. Overall and durable platelet response was achieved by 34 and 24 patients, respectively.In general, changes in KIT scores by treatment group and overall platelet response status showed numerically greater and more often statistically significant improvements from baseline to each assessment for children receiving romiplostim (vs placebo) and for platelet responders (vs non-responders) (see Tables 1 and 2). Results based on durable response status were similar to those based on overall response status (data not shown).In the mixed effects analysis, greater improvement from baseline to week 8/16/25 on Parent KIT score was found in the romiplostim group vs placebo (by approximately 8 points, p-value<0.05); no significant difference was found between groups for Child KIT score.Conclusion: Romiplostim treatment is associated with reduced parental burden (measured by Parent KIT score). In some instances sample sizes were small for other KIT versions; therefore, results should be interpreted with caution.Table 1Mean Change from Baseline in KIT Scores by Treatment ArmKIT VersionAssessment week (sample size for romiplostim, placebo)Romiplostim Mean (95% CI)PlaceboMean (95% CI)Child8 (n=28,11) 16 (n=27,10) 25 (n=28,11)9 (4, 15) 11 (5, 16) 14 (7, 20)9 (1, 18) 8 (-3, 20) 10 (-1, 20)Parent/Proxy8 (n=8,2) 16 (n=8,3) 25 (n=9,3)-0.9 (-7, 5) -0.4 (-12, 11) 8 (2, 13)-40 (-108, 23) -1 (-86, 84) -10 (-80, 59)Parent8 (n=40,16) 16 (n=39,17) 25 (n=37,16)13 (10, 17) 15 (10, 21) 18 (12, 23)4 (-6, 13) 12 (4, 20) 13 (4, 22)Table 2Mean Change from Baseline in KIT Scores by Overall Platelet ResponseKIT VersionAssessment week (sample size for responders, non-responders)Responders Mean (95% CI)Non RespondersMean (95% CI)Child8 (n=23,17) 16 (n=22,16) 25 (n=23,16)11 (4, 18) 11 (4, 18) 16 (8, 24)4 (-5, 12) 8 (1, 15) 8 (1, 15)Parent/Proxy8 (n=7,5) 16 (n=8,5) 25 (n=8,6)0.9 (-7, 9) 4 (-10, 18) 9 (1, 17)-15 (-44, 13) -4 (-31, 22) -3 (-23, 17)Parent8 (n=30,26) 16 (n=30,26) 25 (n=29,24)11 (7, 14) 14 (7, 20) 17 (10, 24)10 (3, 18) 15 (9, 21) 15 (9, 21) DisclosuresMathias:Amgen: Research Funding. Li:Amgen: Employment, Other: Stock Ownership. Eisen:Amgen Inc: Employment, Other: stock ownership. Carpenter:Amgen: Employment, Other: Stock Ownership. Crosby:Amgen: Research Funding. Blanchette:Bayer Healthcare: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Octapharma: Other: Data Safety Monitoring Board; Pfizer: Honoraria, Membership on an entity's Board of Directors or advisory committees; Baxter Corporation: Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: Data Safety Monitoring Board, Research Funding; Novo Nordisk: Honoraria, Membership on an entity's Board of Directors or advisory committees.

A Phase 3, Randomized, Double-Blind, Placebo-Controlled Study to Determine the Safety and Efficacy of Romiplostim in Children with Immune Thrombocytopenia (ITP)

Introduction: Approximately 20% of children diagnosed with ITP have chronic thrombocytopenia, some requiring immunosuppressive treatments. The TPO receptor agonist romiplostim could be a treatment option for symptomatic children with ITP. Methods: In this phase 3, double-blind study, children with ITP for ≥6 months were randomized to weekly romiplostim or placebo (2:1) for 24 weeks, with the dose adjusted weekly from 1-10 μg/kg to target platelet counts of 50-200×109/L. Platelet response was defined as platelet counts ≥50×109/L any week of weeks 2-25 (excluding 4 weeks after rescue medication use). The 1° endpoint, durable platelet response, was defined as ≥6 weekly platelet responses during the final 8 weeks, weeks 18-25. Overall platelet response was defined as ≥4 weekly platelet responses during weeks 2-25. Antibodies to romiplostim or TPO were assayed at baseline and weeks 12 and 25. The Kid9s ITP Tool (KIT), in which higher scores reflect improved quality of life, was administered to children and their parents. Results: Patients (n = 62) had median (range) age 9.5 (3-17) years, ITP duration 2.1 (0.5-10.7) years, and baseline platelet counts 18 (1-94) × 109/L; 44% were male. Sixty-six percent of patients were Caucasian, 13% African American, 8% Asian, and 15% other. For the 1° endpoint, measured in the final 8 weeks after 16 weeks of dose titration, rates of durable platelet response were romiplostim: 52% and placebo: 10% (p Conclusions: In children with symptomatic ITP of ≥6 months duration, romiplostim was effective in inducing high rates of durable and overall platelet responses. There were no new safety signals. By the final 8 weeks of the study, noncutaneous bleeding was decreased with romiplostim. Romiplostim may be a viable treatment option for children with symptomatic chronic ITP. Disclosures Tarantino:Grifols: Honoraria, Membership on an entity9s Board of Directors or advisory committees, Research Funding, Speakers Bureau; BPL: Membership on an entity9s Board of Directors or advisory committees; Baxter: Membership on an entity9s Board of Directors or advisory committees, Research Funding; Novo Nordisk: Membership on an entity9s Board of Directors or advisory committees, Research Funding, Speakers Bureau; Octapharma: Membership on an entity9s Board of Directors or advisory committees; Pfizer: Membership on an entity9s Board of Directors or advisory committees; Cangene: Research Funding; UptoDate, Inc.: Patents & Royalties: royalties; Amgen, Inc: Membership on an entity9s Board of Directors or advisory committees. Off Label Use: Romiplostim is indicated for use in adults with chronic immune thrombocytopenia who have had an insufficient response to corticosteroids, immunoglobulins, or splenectomy. The use of romiplostim in children with ITP is investigational.. Bussel:Amgen, Cangene, GlaxoSmithKline (GSK), Genzyme, IgG of America, Immunomedics, Ligand, Eisai, Shionogi and Sysmex: Research Funding; Portola: Consultancy; Amgen, GSK, Ligand, Shionogi, and Eisai: Other: Advisory board. Blanchette:Baxter Corporation, Bayer Healthcare, Novo Nordisk, Pfizer: Honoraria; Baxter Corporation, Bayer Healthcare: Research Funding; Baxter Corporation, Bayer Healthcare, Novo Nordisk, Pfizer; Data Safety Monitoring Board Baxter Corporation, Octapharma: Other: Advisory board; Baxter Corporation, Octapharma: Other: Data Safety Monitoring Board. Morales:CSL Behring: Membership on an entity9s Board of Directors or advisory committees; Baxter: Membership on an entity9s Board of Directors or advisory committees. Carpenter:Amgen Inc.: Employment, Other: Stockholder. Nie:Amgen Inc.: Employment, Other: Stockholder. Eisen:Amgen Inc.: Employment, Other: Stockholder.

Eltrombopag for children with chronic immune thrombocytopenia (PETIT2): a randomised, multicentre, placebo-controlled trial

The thrombopoietin receptor agonist eltrombopag has been shown to be safe, tolerable, and effective for adults with chronic immune thrombocytopenia. We aimed to investigate the safety and efficacy of eltrombopag for children with chronic immune thrombocytopenia. PETIT2 was a two part, randomised, multicentre, placebo-controlled study done at 38 centres in 12 countries (Argentina, Czech Republic, Germany, Hong Kong, Israel, Italy, Russia, Spain, Taiwan, Thailand, UK, and USA). Paediatric patients aged 1-17 years who had chronic immune thrombocytopenia and platelet counts less than 30 × 10(9) per L were randomly assigned (2:1) to receive eltrombopag or placebo. We stratified patients by age into three cohorts (patients aged 12-17 years, 6-11 years, and 1-5 years) before randomly entering them into a 13 week, double-blind period. Randomisation was done by the GlaxoSmithKline Registration and Medication Ordering System and both patients and study personnel were masked to treatment assignments. Patients who were allocated eltrombopag received tablets (except for those aged 1-5 years who received an oral suspension formulation) once per day for 13 weeks. Starting doses for patients aged 6-17 were based on bodyweight, and ethnic origin and ranged between 50 mg/day and 25 mg/day (starting dose for patients aged 1-5 years was 1·2 mg/kg/day or 0·8 mg/kg/day for east Asian patients). Patients who completed the double-blind period entered a 24 week open-label treatment period in which all patients received eltrombopag at either the starting dose (if they were formerly on placebo) or their established dose. The primary outcome was the proportion of patients achieving platelet counts of at least 50 × 10(9) per L in the absence of rescue therapy for 6 or more weeks from weeks 5 to 12 of the double-blind period. The intention-to-treat population included in the efficacy assessment consisted of all patients who were randomly assigned to one of the treatment groups, and the safety population included all patients who received at least one dose of study drug. This trial is registered with ClinicalTrials.gov, number NCT01520909. Beginning in March 15, 2012, 92 patients were enrolled, and the trial was completed on Jan 2, 2014. 63 patients were assigned to receive eltrombopag and 29 were assigned to receive placebo. In the double-blind period, three patients discontinued treatment because of adverse events: two patients in the eltrombopag group withdrew because of increased liver aminotransferases and one in the placebo group withdrew because of abdominal haemorrhage. 25 (40%) patients who received eltrombopag compared with one (3%) patient who received placebo achieved the primary outcome of platelet counts of at least 50 × 10(9) per L for 6 of the last 8 weeks of the double-blind period (odds ratio 18·0, 95% CI, 2·3-140·9; p=0·0004). Responses were similar in all cohorts (eltrombopag vs placebo: 39% vs 10% for patients aged 12-17 years, 42% vs 0% for patients aged 6-11 years, and 36% vs 0% for patients aged 1-5 years). Proportionately fewer patients who received eltrombopag (23 [37%] of 63 patients) had WHO grades 1-4 bleeding at the end of the double-blind period than did those who received placebo (16 [55%] of 29 patients); grades 2-4 bleeding were similar (three [5%] patients who received eltrombopag vs two [7%] patients who received placebo). During the 24-week open-label treatment period, 70 [80%] of 87 patients achieved platelet counts of 50 × 10(9) per L or more at least once. Adverse events that occurred more frequently with eltrombopag than with placebo included nasopharyngitis (11 [17%] patients), rhinitis (10 [16%] patients), upper respiratory tract infection (7 [11%] patients), and cough (7 [11%] patients). Serious adverse events occurred in five (8%) patients who received eltrombopag and four (14%) who received placebo. Safety was consistent between the open-label and double-blind periods. No deaths, malignancies, or thromboses occurred during the trial. Eltrombopag, which produced a sustained platelet response in 40% of patients with chronic immune thrombocytopenia, is a suitable therapeutic option for children with chronic symptomatic immune thrombocytopenia. We identified no new safety concerns and few patients discontinued treatment because of adverse events. GlaxoSmithKline.

Single course of high dose dexamethasone is more effective than conventional prednisolone therapy in the treatment of primary newly diagnosed immune thrombocytopenia.

IntroductionImmune thrombocytopenia (ITP) is an immune disorder commonly presents as isolated thrombocytopenia. Generally corticosteroids are the main treatment of ITP. This study was designed to evaluate effectiveness of high dose dexamethasone comparing conventional corticosteroid therapy in the treatment of ITP.Materials and methodsIn a randomized prospective study, sixty adult patients with newly diagnosed primary symptomatic ITP (Platelet count < 20,000) were evaluated. Patients divided into two groups. In group A, thirty patients (mean age of 24.9 years) received Dexamethasone 40 mg/IV/daily for four days (10 mg/q6h); and then Prednisolone 1 mg/kg/day/PO with rapid tapering of prednisolone (10 mg/week). From the other hand, in group B, thirty patients (mean age of 27.2 years) were treated with Prednisolone 1 mg/kg/day/PO for four weeks, then the drug tapered weekly.ResultsAll the patients in group A showed favorable response within the first seven days, 27 cases presented complete response (CR) and three cases revealed response (R). In group B, 11 cases had CR, 13 cases showed R and six cases had No response (NR). After three months, rates of CR were 80% and 23.3% in group A and B; respectively. Responses were 16.7% and 33.3%, NRs were 6.6% and 43.3% in group A and B; respectively (P < 0.0001). After 6 months, CR was 73.3% vs.16.7%, and R was 16.7% vs.36.7% and NR was 10% vs. 46.7% in group A and B; respectively (P < 0.0001). After 12 months, there was no change in response rate in group A, but in group B 53% were non responsive, 40% showed R (chronic ITP) and complete response was observed only in 6.7% (P < 0.0001). Three cases in group A and 12 cases in group B had needed splenectomy (P < 0.00002).ConclusionWe showed that high dose dexamethasone is more effective than conventional steroid therapy in newly diagnosed ITP as initial treatment with less relapses and toxicities.

Association between drug use and acute immune thrombocytopenia in adults: a case-control study from the Berlin Pharmacovigilance Center PVZ-FAKOS

Background and Aim: Drug induced acute immune thrombocytopenia (ITP) can be triggered by numerous medications. Aim of our study was to quantify the risk of acute ITP for a wide range of drugs. Materials and Methods: Case-control study including 135 cases of acute ITP leading to hospitalization and 731 control patients aged 18 years and older. Cases were defined as patients with idiopathic or symptomatic ITP and patients with suspected drug induced ITP who had a platelet count ≤100.000/µl. Patients with heparin-induced immune thrombocytopenia were not included as cases. Cases and controls were recruited in 51 hospitals in Berlin within the framework of the active surveillance conducted by the Berlin Pharmacovigilance Centre. Detailed drug information was obtained in a standardized personal interview. Odds ratios of ITP associated with drug exposure within one week before the index date (onset of ITP, day of hospital admission for controls) were calculated by logistic regression analysis adjusting for sex and age. Results: Use of triamteren combined with hydrochlorothiazide (adjusted OR 4.9; 95% CI, 1.2–19), drospirenone combined with ethinylestradiol (OR 7.4; CI 1.2–58.4), cotrimoxazole (OR 7.1; CI 1.5–37), and amitriptyline (OR 12.8; CI 1.2–279.3) were significantly associated with an increased risk of developing acute ITP. Increased risk estimates, although not significant, were observed for phenprocoumon (OR 2.0; CI 0.9–4.2), amlodipine (OR 2.1; CI 0.9–4.6), and chlormadinone combined with ethinylestradiol (OR 8.9; CI 0.8–194.4). No increased risks were observed for non-steroidal anti-inflammatory drugs (NSAIDs), ACE inhibitors or antidiabetic drugs. Conclusion: Our study showed increased risks for several medications. Drug induced acute ITP should be considered in a patient presenting with unexpected sudden thrombocytopenia who is receiving these medications. Acknowledgement: PVZ-FAKOS is being funded by the Federal Institute for Drugs and Medical Devices, Germany

Low‐dose rituximab in adult patients with primary immune thrombocytopenia

Rituximab 375 mg/m(2) weekly for 4 wks has significant activity in adults with primary immune thrombocytopenia (ITP). In this setting, several evidences support the possible use of lower doses of rituximab. To investigate the activity of low-dose rituximab as salvage therapy in previously treated symptomatic ITP. Forty-eight adult patients were treated prospectively with rituximab 100 mg weekly for 4 wks. Overall and complete responses (CR) (platelet level ≥ 50 and 100 × 10(9) /L) were 60.5% and 39.5%, respectively. In responders, the median time to response was 35 d (range: 7-112 d). The median time of observation was 18 months (range 3-49 months). Sixteen of 29 responding patients (55%) relapsed and 14 needed further treatments. The 12- and 24-month cumulative relapse-free survival was 61% and 45%, respectively. In univariate analysis, CR rate was in inverse relation with weight OR=0.95, CI(95%) [0.91; 0.99] (P=0.019) and age OR=0.96, CI(95%) [0.93; 0.99] (P=0.047). Cox regression model showed that relapse probability increases as weight (HR=1.06, CI(95%) [1.0031; 1.111]) and period between diagnosis and rituximab therapy (HR=1.01, CI(95%) [1.002; 1.017]) increase. One patient developed an interstitial pneumonia 1 month after the end of rituximab treatment. No other infectious, hematologic or extra-hematologic complications were documented during follow-up. Low-dose rituximab is active in ITP but has moderate long-term effect. A comparative study with standard dose is warranted.

Anti-RhD immunoglobulin in the treatment of immune thrombocytopenia

Immune thrombocytopenia (ITP) is an acquired bleeding autoimmune disorder characterized by a markedly decreased blood platelet count. The disorder is variable, frequently having an acute onset of limited duration in children and a more chronic course in adults. A number of therapeutic agents have demonstrated efficacy in increasing the platelet counts in both children and adults. Anti-RhD immunoglobulin (anti-D) is one such agent, and has been successfully used in the setting of both acute and chronic immune thrombocytopenia. In this report we review the use of anti-D in the management of ITP. While the FDA-approved dose of 50 mg/kg has documented efficacy in increasing platelet counts in approximately 80% of children and 70% of adults, a higher dose of 75 microg/kg has been shown to result in a more rapid increase in platelet count without a greater reduction in hemoglobin. Anti-D is generally ineffective in patients who have failed splenectomy. Anti-RhD therapy has been shown capable of delaying splenectomy in adult patients, but does not significantly increase the total number of patients in whom the procedure can be avoided. Anti-D therapy appears to inhibit macrophage phagocytosis by a combination of both FcR blockade and inflammatory cytokine inhibition of platelet phagocytosis within the spleen. Anti-RhD treatment is associated with mild to moderate infusion toxicities. Rare life-threatening toxicities such as hemoglobinuria, acute renal failure and disseminated intravascular coagulation have been reported. Recommendations have been proposed to reduce the risk of these complications. Anti-D immunoglobulin can be an effective option for rapidly increasing platelet counts in patients with symptomatic ITP.

Intravenous gammaglobulin has no advantages over oral corticosteroids as primary therapy for adults with immune thrombocytopenia: A prospective randomized clinical trial

Symptomatic immune thrombocytopenia in adults is potentially lethal, and, when conventionally treated with oral corticosteroid agents, approximately two thirds of patients will have some response in platelet count, but this is seldom durable. Since cytotoxic drugs are of limited benefit at this stage, splenectomy becomes necessary in 70% of patients. Intravenous gammaglobulin has been advocated as an alternative to prednisone as the primary form of treatment. A prospective, randomized comparison was carried out between oral prednisone (1 mg/kg/day; group 1; n = 17), high-dose intravenous gammaglobulin (400 mg/kg on days 1 through 5; group 2; n = 13), or a combination of both agents given on the same schedule (group 3; n = 13). The groups were well matched clinically and hematologically. No mortality occurred after initiating therapy, but one patient experienced a cerebrovascular accident. Response, defined as a platelet count greater than 50 × 10 9/L, was achieved in 82%, 54%, and 92% of patients in groups 1, 2, and 3, respectively, but was only significant between groups 2 and 3 (P = 0.0365). The median times to peak platelet counts were 8.5 days (range 7 to 21 days), 7 (range 5 to 10 days), and 7 (range 3 to 23 days), respectively. Although there was a trend in favor of the steroid-administered groups, relapse was not significantly different, which occurred at a median of 184, 32, and 76 days, respectively, nor was the average time to splenectomy different at 339, 59, and 98 days, respectively. At a minimum of 2 years of follow-up, 5 of 17 in group 1, 2 of 13 in group 2, and 1 of 13 in group 3 had achieved platelet counts of greater than 100 × 10 9/L and, therefore, did not require splenectomy. In contrast, where this indication was present for failure to respond, 8 of 12 (67%) in group 1, 4 of 8 (50%) in group 2, and 9 of 12 (75%) in group 3 remain in complete remission. Significantly more patients in group 2 than group 3 experienced a relapse (P = 0.0365). It is concluded that in previously untreated adults with symptomatic immune thrombocytopenia, gammaglobulin offers no advantage over conventional corticosteroid administration as the primary form of therapy. Additionally, more intense immunosuppression, resulting from the use of both agents combined, is no better than single agent corticosteroid agents and appears to be an unnecessary and unwarranted expense.