Treatment Of Immune Thrombocytopenic Purpura Research Articles

Targeted therapies for immune thrombocytopenic purpura: a meta-analysis of randomized controlled trials.

Several targeted therapies have been approved in recent years for second-line treatment of immune thrombocytopenic purpura (ITP), providing an alternative to rituximab and splenectomy. The extent to which these drugs reduce bleeding risk has not been well defined. Targeted therapies recently approved for the treatment of ITP in adults were identified through a search of recently published professional guidelines. Randomized controlled trials (RCTs) supporting regulatory approval were identified through a search of drug labels on FDA@gov. Odds ratios (ORs) and associated 95% confidence intervals (CIs) were computed for pre-specified efficacy outcomes including platelet recovery to ≥ 50,000/µL, major and minor bleeding events, and survival. ORs for all adverse events were also computed. Four targeted therapies were identified, including three thrombopoietin receptor agonists and one tyrosine kinase inhibitor. Six RCTs, comprising 752 patients, were included in the meta-analysis. More patients treated with targeted therapies for ITP as compared to placebo achieved platelet counts over ≥ 50,000/µL (OR 8.29, 95% CI 5.59-12.29). Compared to placebo, targeted therapies for ITP were associated with significantly lower odds for major bleeding (OR 0.43, 95% CI 0.21-0.91), minor bleeding (OR 0.66, 95% CI 0.45-0.97), and with numerically lower mortality rates (OR 0.24, 95% CI 0.05-1.07). The odds for adverse events were comparable between the two arms (OR 1.43 95% CI 0.76-2.67). Compared to placebo, targeted therapies for ITP increase platelet counts, decrease bleeding events, and show a trend towards lower mortality, without increased toxicity. These findings support their use as a second-line ITP treatment.

A real-world study of immune thrombocytopenia management during the COVID-19 pandemic in the UK.

SummaryThe COVID‐19 pandemic has created many challenges in the management of immune thrombocytopenic purpura (ITP). The recommendation for avoidance of steroids by WHO led to the off‐licence use, supported by NHS England, of thrombopoietin mimetics (TPO‐RA) for newly diagnosed or relapsed ITP. This is a real‐world prospective study which investigated the treatment patterns and outcomes in this setting. Twenty‐four hospitals across the UK submitted 343 cases. Corticosteroids remain the mainstay of ITP treatment, but TPO‐RAs were more effective. Incidental COVID‐19 infection was identified in a significant number of patients (9·5%), while 14 cases were thought to be secondary to COVID‐19 vaccination.

Incidence and Outcome of Severe Thrombocytopenia Associated with Zika Virus Infection - Puerto Rico, 2016

Introduction: There are many etiologies for thrombocytopenia, such as viral suppression, disseminated intravascular hemolysis, and immune thrombocytopenic purpura (ITP). Zika virus (ZIKV) recently emerged in the Americas and was first detected in Puerto Rico in late 2015. ZIKV disease is generally mild; however, it has been infrequently associated with life-threatening outcomes including severe thrombocytopenia. We sought to define incidence and outcomes of ZIKV disease patients with thrombocytopenia.Methods: We reviewed the medical records of patients with reported thrombocytopenia (platelet count ≤ 100,000 cells/µL) among patients with ZIKV disease (defined by detection of ZIKV nucleic acid by RT-PCR or anti-ZIKV IgM antibody by ELISA and the presence of symptoms) that had been reported via passive surveillance. Among patients with confirmed thrombocytopenia, we collected data on medical history, interventions, and patient outcomes. Cases of severe thrombocytopenia were defined by: a) platelet count <20,000 cells/µL; or b) platelet count <50,000 cells/µL with a clinical diagnosis of and treatment for ITP. Cases in which another likely cause of thrombocytopenia was identified (e.g., sepsis, immunosuppression) were excluded from analysis. Data were collected in REDCap®.Results: Of 37,878 patients with ZIKV disease reported during 2016, a total of 436 had reported thrombocytopenia. Among patients with medical records available for review, 48 (0.1%) had confirmed thrombocytopenia in the absence of an identified etiology. Twelve of these 48 patients (25%) had severe thrombocytopenia (Table 1), and 36 (75%) had non-severe thrombocytopenia.Median age of patients with severe and non-severe thrombocytopenia was 39.5 years (range: 2-88) and 49 years (range: 1-88 years), respectively; 7 (58%) and 19 (53%) were male. Two (17%) patients with severe and 3 (8%) with non-severe thrombocytopenia had a history of ITP. All patients reported recent illness, which most frequently included rash (73%) and/or fever (77%). Median nadir platelet count of patients with severe and non-severe thrombocytopenia was 12,500 cells/µL (range: 1,000-30,250) and 70,000 cells/µL (range: 24,000-100,000), respectively, which occurred a median of 5.7 days (range: 1.4-15.6) and 4.5 days (range: 0.4-34.1) after symptom onset. Blood smears were performed in 9 (75%) patients with severe and 18 (50%) with non-severe thrombocytopenia. No patients with severe thrombocytopenia and 1 (2.8%) patient with non-severe thrombocytopenia had fragmented red blood cells; visualization of platelets on smear was consistent with low platelet counts. Whereas 11 (30.6%) patients with non-severe thrombocytopenia had petechiae, hematuria, or gingival bleeding, all (100%) patients with severe thrombocytopenia had hemorrhagic manifestations including petechiae (66.7%), hematuria (33.3%), ecchymoses (50%), gastrointestinal bleeding (25%), or intracranial hemorrhage (8.3%). Only patients with severe thrombocytopenia were diagnosed with ITP. Only patients with severe thrombocytopenia received platelet transfusion (n = 4; 33.3%) and/or intravenous immunoglobulin (IVIG) (n = 5; 41.7%). The patients with severe thrombocytopenia that received IVIG all had an up-trending platelet count after IVIG administration. Eight (66.6%) patients with severe thrombocytopenia and 9 (25.0%) with non-severe thrombocytopenia received steroids. Among those who received platelet transfusions, the median platelet count increase following transfusion was 6,000 cells/µL; 25% had a decreased platelet count following transfusion. Outcomes among patients with severe or non-severe thrombocytopenia included hospitalization (100% vs. 53%), admission to the intensive care unit (33% vs. 0%), and death (8.3% vs. 0%).Conclusions: Thrombocytopenia appears to be an uncommon occurrence in patients with ZIKV infection. Though rare, severe thrombocytopenia associated with ZIKV disease can be fatal; treatment is necessary. Platelet transfusions alone may not be effective, whereas administration of corticosteroids and IVIG may be of benefit in some cases. Further study is needed to characterize the pathogenesis of ZIKV-associated severe thrombocytopenia and interventions associated with survival. Appropriate diagnosis of the underlying etiology of thrombocytopenia is time-sensitive and crucial to improving patient outcome. [Display omitted] DisclosuresNo relevant conflicts of interest to declare.

Subcutaneous Rituximab Given to Patients for Other Indications Than CD20+ B-Cell Lymphoma: A Monocentric Study of 20 Cases

Background: Rituximab (R) is the first anti-CD20 monoclonal antibody that has demonstrated efficacy in patients with various B-cell lymphoid malignancies. Administered intravenously (IV), it has been shown to be also efficient to treat other hematologic situations such as Epstein-Barr virus (EBV) reactivation, especially after hematopoietic stem cell transplantation (HSCT), or immune thrombocytopenic purpura (ITP). Finally, survivals of younger patients with CD20-positive Philadelphia-negative acute lymphoblastic leukemia (ALL) are significantly increased when combining IV-R with chemotherapy. Recently, a subcutaneous (SC) formulation of R (SC-R) has been approved for B-cell lymphoma that provides a highly-concentrated fixed dose of rituximab with the advantages of reducing treatment times and nursing workload and potentially providing greater comfort and convenience for patients and lesser dosing errors, shorter preparation time or reduced drug wastage for pharmacy dispensers. At our knowledge, there is no published data addressing the tolerance and the efficacy of SC-R given to patients with other indications than CD20+ B cell lymphoma.Patients and Methods: We have retrospectively analyzed all cases who received at our center at least one dose of SC-R but with no lymphoma indication. Three situations were considered: EBV reactivation (post transplantation or not), ITP or ALL treatment. All patients received their first(s) dose(s) of R IV (375mg/m2/injection) and a switch to SC-R (1400mg/injection) was realized only if they didn't experience grade 3 or 4 adverse event (AE) with IV formulation. Our rules is to provide R (IV+SC) weekly, up to 4 doses for ITP (in case of platelets counts <30000/mm3 with no response to corticosteroids or immunoglobulin) and EBV reactivation (in case of 2 positive PCR > 4 log10 number of viral DNA copies), while GRAALL schedule is followed for R administration in CD20+ ALL patients. Tolerance of SC-R (mainly infusion related or late-onset neutropenia (LON)) was appreciated using National Cancer Institute Common Terminology Criteria for Adverse Events v4.03 and any grade 3 or 4 AE related to SC-R was sufficient to stop treatment. Success of SC-R was defined by either a documentation of a negative EBV PCR or absence of ALL relapse or platelets counts reaching at least 100000/mm3.Results: Between February 2016 and June 2017, 20 patients (male n=17) with a median age of 60 years old (range: 33-76) received SC-R in our institution. Overall, 102 R including 58 SC-R were administered with a median of 3 R (range: 2-26) and 2 SC-R (range: 1-16) injection per patient, respectively. The median follow-up from the last SC-R administration was 4.4 months (range: 0.2-11.2 months).No grade 3/4 infusion related reaction were documented in this series while 4 out of 16 assessable cases presented with LON at a median of 45 days (range: 44-70) after the last SC-R injection. Neutropenia lasted a median of 6 days (range: 4-9) with the help of GCSF and was not responsible for complication.Eleven cases received SC-R for EBV reactivation (including 8 after allogeneic transplant and 3 in a context of aplastic anemia) with a median of 3 R (IV+SC, range: 1-4) and 2 SC-R (range: 1-3) injections. One patient died of concomitant invasive fungal infection and was not evaluable for efficacy. All of the ten other patients were documented with negative EBV PCR after treatment.Four patients received SC-R during ALL first line treatment with a median of 11 R (IV+SC, range: 3-26) and 6 SC-R (range: 1-16) injections. Two patients have received more than the number of R infusion scheduled (17 and 26) because of high toxicity related to the chemotherapy and it was chosen to deliver a maintenance therapy with vincristine/SC-R and prednisone. None of the four ALL patients had relapsed so far at 2, 8, 18 and 20 months from diagnosis with a median follow up of 13 months (2-20).Five patients received SC-R for ITP with a median of 3 R (IV+SC, range: 3-4) including 2 SC-R (range: 1-3) injections. Three patients obtained platelets count improvement within a median of 28 days (19-48) and none relapsed so far.Conclusion: SC-R seems to demonstrate a comparable efficacy/safety profile as IV-R when given to patients for other indications than CD20+ B-cell lymphoma. There should be no restriction to use SC-R for these patients in the future as it may improve quality of care for both patient and health providers. DisclosuresTouzeau:AbbVie: Research Funding. Le Gouill:Roche: Consultancy, Honoraria, Research Funding; janssen: Consultancy, Honoraria; servier: Consultancy, Honoraria, Research Funding; bayer: Membership on an entity's Board of Directors or advisory committees; celgene: Honoraria, Research Funding. Moreau:Celgene, Janssen, Takeda, Novartis, Amgen, Roche: Membership on an entity's Board of Directors or advisory committees; Amgen: Honoraria; Novartis: Consultancy, Honoraria; Bristol-Myers Squibb: Honoraria; Celgene: Consultancy, Honoraria; Takeda: Honoraria; Janssen: Consultancy, Honoraria; Millennium: Consultancy, Honoraria; Onyx Pharmaceutical: Consultancy, Honoraria.

Innovative methods of treatment of immune thrombocytopenic purpura in young people

This article is about describing innovative methods of treatment of immune thrombocytopenic purpura in young people. Moreover, a great many useful instructions are given in order to enhance immune system.

Eltrombopag Can Achieve Treatment Free Remission as Upfront Therapy for Patient with Immune Thrombocytopenia

Immune Thrombocytopenic purpura (ITP) is an immune mediated thrombocytopenia caused by autoantibodies directed against platelet antigens which leads to destruction of the platelets by the spleen and inability of the bone marrow to restore normal counts. The main treatment for ITP is immunosuppressive medication and the first line treatment is glucocorticoids, intravenous immune globulin (IVIG) and Intravenous anti-D immune globulin. Here we report a 45-year old lady who was diagnosed with ITP and achieved treatment free remission after with Eltrombopag as upfront.

Induction of the remission of immune thrombocytopenic purpura

Abstract. A review of the literature on remission of immune thrombocytopenic purpura in children and a retrospective analysis of its course in a young patient who was successively applied, first to no avail, standard drug therapy, and then, due to the lack of effect, a physiotherapy technique based on the principles of activation therapy. It is known that immune thrombocytopenic purpura is a rare acquired autoimmune disease characterized by isolated thrombocytopenia with the occurrence of hemorrhagic syndrome of varying severity, which can lead to fatal bleeding. At the same time, antiplatelet antibodies are detected only in half of patients suffering from immune thrombocytopenic purpura, and therefore are not a necessary criterion for diagnosis, which in turn makes it difficult to diagnose the disease and does not allow them to be used as a criterion for the effectiveness of treatment. Despite the fact that in childhood, most cases of immune thrombocytopenic purpura occur in acute form, often with the development of spontaneous remission, but in a significant part of patients, relapses of the disease are accompanied by significant thrombocytopenia, hemorrhagic syndrome, and a decrease in the quality of life, which requires specific therapy up to splenectomy. When using the Reverse wave technique in the treatment of immune thrombocytopenic purpura, a stable, long-term remission was achieved in a young patient. The prospects of studying the application of this physiotherapy technique in clinical practice are discussed.

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

Traitements de première ligne au cours du purpura thrombopénique immunologique de l'adulte : état des lieux et perspectives

The first line treatment of immune thrombocytopenic purpura (ITP) is well established and based on short course of corticosteroids associated with intravenous immunoglobulins (IVIg) for the most severe forms. Predniso(lo)ne is the corticosteroid agent usually given but dexamethasone appears as an alternative. Some guidelines recommend to use dexamethasone as first line when a rapid increase of platelet count is required. Dexamethasone could be used rather than IVIg for moderate to severe but non life-threatening bleeding manifestations. Other therapeutic options such as anti FcRn monoclonal antibodies or recombinant FcγR currently in development for ITP could be an option in the future. In newly diagnosed ITP, we unfortunately lack robust predictive risk factors of severity and chronic outcome. Identifying such factors could be helpful for considering the early use of some treatments which are commonly used as second or third line.

Laboratory Tests Used in the Diagnosis of Immune Thrombocytopenia and General Treatment Approaches

Immune thrombocytopenia currently called under its’ new name, immune thrombocytopenic purpura (ITP) is a disease characterized by thrombocytopenia, in which the body attacks its own platelets due to the disorders in immune system. The pathophysiology of this disease includes increased platelet destruction and most megakaryocyte production in bone marrow. The most common clinical manifestation of ITP is mild or severe progressive bleeding that could result in death. ITP is generally named as primary or secondary ITP according to thrombocytopenia severity, disease duration, bleeding status and secondary occurrence of the disease. Currently for diagnosis, despite the blood count, antiglobulin test and laboratory tests that can detect platelet-bound antibodies, they are not enough for definitive diagnosis. Like the difficulty in diagnosis, ITP treatment is quite complicated which varies depending on age, characteristics and risk of the patient. It is classified as first, second and third-line treatment options. Also, depending on the condition of patients, combined treatment might be an option which increases the complexity of the treatment. Unfortunately, discussions related to different clinical applications in diagnosis and treatments continue recently. For this reason, we considered that preparation of a review containing recent updates in diagnostic approaches and treatment options in ITP will be remarkable and beneficial for physicians interested in this subject.

The use of an Alpine climate in the treatment of immune thrombocytopenic purpura (ITP) in children of the Kyrgyz Republic

The objective of the study is to evaluate the effectiveness of the use of alpine (high-altitude) climatotherapy in the chronic form of immune thrombocytopenia in children. The article presents the results of the treatment of immune thrombocytopenia in children during high altitude climatotherapy. For this type of treatment, the alpine climate of the Tuya-Ashu pass (3200 meters above sea level) in the Kyrgyz Republic used. A 40-day stay in the highlands contributes to the relief of hemorrhagic syndrome and a significant increase in platelet count. Evaluation of the treatment results showed that out of 32 children who received alpine (high-altitude) climatotherapy once, 2 achieved complete and 14 had partial remission. In 11 children, the improvement of clinical and hematological parameters was temporary, and the absence of effect recorded in 5 patients. 50% of children with chronic immune thrombocytopenia (ITP) responded positively to a single course of treatment. Repeated courses of treatment led only to an improvement in clinical and haematological parameters. In our study, we have a case of a complete recovery of a child with immune thrombocytopenia (ITP) after 5 treatments in high altitude conditions.

Outcome of Immune Thrombocytopenic Purpura In a Tertiary Care Centre

Background : The study aimed to demonstrate the pattern of clinical presentations and outcome of Immune Thrombocytopenic Purpura (ITP) in Bangabandhu Sheikh Mujib Medical University (BSMMU) Dhaka.&#x0D; Materials and methods: A retrospective study was conducted by record reviewing and analyzing the data of 103 patients of acute ITP, ageing between 1-16 years, at the Department of Paediatric Haematology and Oncology, Bangabandhu Sheikh Mujib Medical University (BSMMU) Dhaka from June 2017 to December 2019. We reviewed the data regarding age, sex, clinical presentations, history of preceding viral infections, vaccination history, laboratory values, different treatment options used and response to the treatment concerning complete response, partial response and poor responders. Statistical analysis performed by using IBM SPSS statistics version 20.&#x0D; Results: We retrospectively reviewed a total of 103 patients. The median age, at the time of presentation, was 5±3.4 years while the mean age was 4.5±2.9 years. The male to female ratio was 1.28:1. Mean platelet count on presentation was 7 x 109/L (Range: 0-24). Twenty three (22.3%) patients had the history of preceding febrile illness. Bruises, petechiae, epistaxis and hematemesis remained the common presentations. Six (5.8%) patients showed spontaneous recovery while 97 (94%) patients received treatment for ITP. Overall, 71 (68.9%) showed a response after treatment. Sixty-two patients (59.22%) showed loss of response and received treatment again. Among these patients, thirty-four patients (33%) developed chronic disease.&#x0D; Conclusion: Majority of patients presenting to our tertiary care centre had severe acute ITP on presentation.After management and follow-up, almost one third of the patients develop chronic disease hence the incidence of developing chronic disease remained high as compared to the other centers.&#x0D; JCMCTA 2019 ; 30 (2) : 81-85

Clinical value of megakaryocytes in the diagnosis and treatment of children with immune thrombocytopenic purpura

Objective To analyze the clinical value of megakaryocytes in the diagnosis and treatment of children with immune thrombocytopenic purpura(ITP). Methods From June 2014 to January 2018, the clinical data of 110 children with ITP diagnosed and treated in Zhucheng People's Hospital Affiliated to Weifang Medical College were analyzed and followed up for more than 1 year.The children were divided into two groups according to whether the duration of the disease was morethan 12 months(chronic group and non-chronic group). Gender, age, initial course of disease, platelet count, lymphocyte count, megakaryocyte count, white blood cell count, and initial treatment regimen were analyzed and compared between the two groups.Multivariate analysis was used to analyze the independent influencing factors of chronic ITP.The clinical value of the initial diagnosis and lymphocyte counts in evaluation of the effects of chronic ITP and initial treatment were analyzed.The clinical value of megakaryocyte in the assessment of initial treatment was analyzed. Results The initial course of disease[(5.8±2.26)d]and megakaryocyte count[(210.28±98.67)/piece] in the chronic groupwere higher than those in the non-chronic group[(3.57±2.05)d, (165.26±78.35)/piece], and the lymphocyte count[(2.87±0.90)×109/L] in the chronic groupwas lower than that in the non-chronic group[(3.66±1.12)×109/L], the differences were statistically significant(t=4.824, 2.299, 3.545, all P 0.05). The initial course of disease was a risk factor for chronic ITP(OR=3.826), while lymphocyte count was a protective factor(OR=0.471). The initial course of disease was evaluated as AUC=0.648 for chronic ITP, with an optimal cut-off value of 4.5 days, a sensitivity of 65.4%, and a specificity of 62.5%.Lymphocyte counts was evaluated as AUC(area under the ROC curve)=0.648 for chronic ITP, the optimal cut-off value was 3.01×109/L, the sensitivity was 59.4%, and the specificity was 78.2%.The initial course of disease and lymphocyte count had no significant value in evaluation of the treatment outcome (P<0.05). The initial treatment of patients with increased megakaryocyte counts was better than those with the normal level, and the difference was statistically significant(Z=6.051, P<0.05). Conclusion The initial course of disease and lymphocyte count can help to assess the duration of ITP in children.Patients with increased bone marrow megakaryocyte counts can achieve better results at initial treatment. Key words: Megakaryocytes; Purpura, thrombocytopenic, idiopathic; Time factors; Lymphocytes; Diagnosis; Treatment outcome; Risk factors; Child

Safety Profile of Fostamatinib, an Oral Spleen Tyrosine Kinase Inhibitor: A Meta-Analysis of Randomized Controlled Trials

Introduction: Fostamatinib, a spleen tyrosine kinase (Syk) inhibitor has been studied in clinical trials of chronic immunologic conditions such as Rheumatoid Arthritis (RA), chronic immune thrombocytopenic purpura (ITP), IgA nephropathy and certain lymphomas. It has recently been granted FDA approval for the treatment of ITP. Fostamatinib inhibits the Syk pathway which is also involved in platelet activation through collagen receptor and the integrin αIIbβ3, which, in theory, would increases the risk of bleeding. Also, by inhibiting Syk, fostamatinib reduces macrophage phagocytosis and may render them ineffective against certain bacteria, hence increasing the risk of serious infections. We sought to examine the side effect profile of Fostamatinib in published and unpublished studies randomized controlled trials (RCT). Methods: A systematic search of scientific databases, major conference abstracts and clinical trial registries was performed. Only Phase 2 and Phase 3 RCTs with a placebo arm were included. For dosing of fostamatinib, we preferentially used the 100mg BID dosing as this is the dose approved by the FDA for ITP and is the dose determined through the large trials in patients with RA, which strikes a balance between benefits and harms. When the 100mg and 150mg dosing were combined (as in the ITP trials), we used data from that arm for the analysis. All major and minor harms specified in the trials were pooled using a random effects model and the risk ratio (RR) and confidence interval (CI) was determined using the Mantel-Haenszel method. An I2 value of less than ≤ 40% was considered minimal heterogeneity. Results: The search found 12 studies involving 1,444 cases and 1,188 controls. Of these, 9 studies examined the use of fostamatinib for RA whereas 2 studies were on ITP, and 1 study was on IgA nephropathy. Commonly encountered side effects of fostamatinib therapy were diarrhea, headache, nausea and hypertension. When compared to placebo, fostamatinib was associated with 19% higher risk of any adverse event (9 studies, RR = 1.19, CI = 1.07 - 1.33, I2 = 40%). Patients who received fostamatinib had a significantly higher risk of developing neutropenia (ANC &lt; 1500/microL) when compared to placebo (8 studies, RR = 4.34, CI = 1.82 - 10.31, I2 = 30%). There was only 1 case of febrile neutropenia in one of the ITP trials. There were no significant differences between the fostamatinib and placebo groups with regard to upper respiratory tract infections (7 studies, RR = 1.43, CI = 0.61 - 3.36, I2 = 49%), urinary tract infections (4 studies, RR = 1.6, CI = 0.78 - 3.28, I2 = 0%) or serious infections (7 studies, RR = 1.18, CI = 0.42 - 3.30, I2 = 0%). However, when compared to placebo, there was a 2.23 times higher risk of developing diarrhea (10 studies, CI = 1.46 - 3.41, I2 = 45%) and hypertension (9 studies, CI = 1.61 - 3.09, I2 = 13%) in the fostamatinib group. Most patients had hypertension at baseline and few needed either medication initiation or adjustment in the fostamatinib cohorts. Fostamatinib also significantly increased liver enzyme (ALT &gt; 3 ULN) when compared to placebo (9 studies, RR = 2.21, CI = 1.18 - 4.14, I2 = 0%). There were higher bleeding events in the fostamatinib group, but there was no significant difference between the treatment and placebo arms (4 studies, RR = 1.06, CI = 0.16 - 6.94, I2 = 45%). There were no significant differences between the treatment and control groups with regard to serious adverse events and mortality. Treatment discontinuation rates due to adverse events were not significantly different between groups. Conclusions: Fostamatinib tends to have a relatively benign side effect profile, with few serious side effects. In congruence of the theoretical higher bleeding risk with Syk inhibition, the bleeding events were slightly higher in fostamatinib group, however there was no statistically significant difference between the treatment and the placebo groups. Similarly, the incidence of neutropenia, though higher in the Fostamatinib group, was rarely associated with fever (1 event among all 12 trials). The incidence of serious infections did not differ significantly between groups. Gastrointestinal and cardiac side effects were transient and did not lead to significantly more treatment discontinuations when compared to placebo. Larger longitudinal studies are needed to better examine the long-term side effects associated with Fostamatinib. Table Disclosures No relevant conflicts of interest to declare.

Teetering on a liver\u2019s edge: a case report highlighting clinical decision-making in thrombocytopenia

BackgroundThis report illustrates the importance of a detailed history and physical exam and careful analysis of hematologic parameters when diagnosing ITP. This case demonstrates that even with subtle deviations from typical ITP findings one must promptly reevaluate the diagnosis. This case also highlights the importance of peripheral smear review by an expert in pediatric hematopathology.Case presentationA previously healthy 10 year-old Asian boy presented with 2 months of easy bruising. Review of systems was negative for any constitutional symptoms. On examination, he appeared well but had numerous large ecchymoses. He had no appreciable lymphadenopathy or splenomegaly. The liver was palpable 1.5 cm below the costal margin. A complete blood count (CBC) showed: platelets = 17 × 109/L, hemoglobin = 128 g/L, white blood cell count = 5.43 × 109/L, and neutrophils = 1.63 × 109/L. A blood smear was reported as normal. Urate was 370 umol/L and lactate dehydrogenase (LDH) was 803 U/L. The child was admitted with a presumptive diagnosis of immune thrombocytopenic purpura (ITP) and treated with intravenous immunoglobulin. The following day, the blood smear was reviewed by a hematopathologist who identified blasts. A bone marrow aspiration (BMA) confirmed the diagnosis of precursor B-cell acute lymphoblastic leukemia.ConclusionIn children presenting with suspected ITP, leukemia should always be considered. A BMA was historically performed on all patients with presumed ITP to rule out leukemia. In 2011, the American Society of Hematology (ASH) stopped recommending routine BMA in patients suspected of having ITP. ASH advises in cases with unusual findings on history, physical examination or CBC, it is reasonable to perform a BMA. Our patient had mild hepatomegaly, which may have qualified him for a BMA. He also had an elevated LDH and urate, which are not listed as criteria for BMA by ASH but were considered atypical for ITP by the clinical team. A literature search did not reveal any primary data assessing these markers.While corticosteroids are a first line treatment in ITP, they must be reserved for when clinicians are confident that the patient does not have leukemia. Steroid administration prior to diagnosing leukemia results in delayed diagnosis and may increase the risk of complications and decrease survival.

Immune Thrombocytopenic Purpura Splenectomy in the Context of New Medical Therapies

BackgroundAs medical therapy improves, splenectomy has been relegated to third- or fourth-line therapy for immune thrombocytopenic purpura (ITP) in many hematologic practices. However, these medications have well-known associated morbidity and changes in treatment algorithms may affect the timing and degree of response to splenectomy as well as complications in heavily treated ITP patients. Materials and methodsThis is a retrospective study of consecutive patients who underwent ITP splenectomy from January 1994 to June 2017. Nonresponders after splenectomy and those with recurrent disease were compared to complete responders. ResultsThe cohort included 84 patients. Median number of medications received before splenectomy was 3 (1-6). 14.3% of patients had a medication-related complication, including heart failure, adrenal insufficiency, diabetes mellitus, infection, and osteoporosis. After splenectomy, 83.5% had a complete response, 7.5% partial response, and 9% no response. Complete response was associated with response to steroids before surgery (P < 0.01). Among responders, 19% had recurrent disease, which was associated with lower platelet count at diagnosis (P < 0.01). Forty-four patients (52.0%) had nonelective splenectomies for persistent bleeding or dangerously low platelets despite maximal medical therapy. Ten patients had Clavien-Dindo grade II or higher surgical complications (11.9%). Seven of these complications were related to recurrent or refractory ITP. ConclusionsMany ITP patients have complications related to medication use, and 52.0% required nonelective splenectomy despite maximal medical therapy. Earlier splenectomy may avoid medication-related complications and may reduce the complications from splenectomy. Splenectomy remains an effective and safe treatment for ITP.

Characteristics, risk factors and management of venous thromboembolism in immune thrombocytopenia: a retrospective multicentre study.

An increased risk of thrombosis has been reported in immune thrombocytopenic purpura (ITP), but the characteristics, risk factors of occurrence, recurrence and management of venous thromboembolic events (VTE) have been poorly investigated. To describe VTE and ITP characteristics, distribution of VTE risk factors and their impact on VTE features and recurrence. A retrospective study of patients with ITP and VTE registered in databases of three reference French centres of ITP. Among 49 patients, 66 VTE were recorded. The platelet count at the time of the first VTE was <100 × 109 /L for 28/43 (65%) patients. In total, 19/48 (40%) patients had at least one positive antiphospholipid test result. For the 10 VTE occurring in eight patients with platelet count <50 × 109 /L, ITP treatment was efficient in 7. One haemorrhagic complication associated with anticoagulant (AC) therapy was recorded. For 31/49 (63%) patients, long-term AC therapy could have been discussed after the first VTE, but only 13 received it. A second VTE occurred in 13 (27%) patients. The risk of recurrence was increased in patients with unprovoked VTE before ITP diagnosis or active cancer. VTE in ITP mainly occurred in the presence of multiple risk factors of TE. A low platelet count does not protect against VTE. Management with AC therapy despite persistently low platelet count seems possible. Risk of VTE recurrence is high, particularly with a history of unprovoked VTE or active cancer. In this setting, indefinite AC therapy could be discussed.

PB2247 ADJUSTED INDIRECT COMPARISON OF ELTROMBOPAG RELATIVE TO RITUXIMAB OR SPLENECTOMY IN SECOND LINE TREATMENT FOR CHRONIC IMMUNE THROMBOCYTOPENIC PURPURA

Background:Current guidelines recommend thrombopoietin receptor agonists (TPO‐RAs: eltrombopag and romiplostim), splenectomy and rituximab as second‐line treatment options for chronic immune thrombocytopenic purpura (ITP). To date no head‐to‐head randomized trial exists comparing these therapies. There is some sparse evidence for indirect comparison between eltrombopag and romiplostim, but no indirect comparison of TPO‐RAs with splenectomy or rituximab for ITP patients eligible to splenectomy. This is because evidence for the effect of rituximab and splenectomy in ITP comes from single arms trials and from observational studies or case series, respectively.Aims:To apply indirect adjusted comparison methods to assess the relative efficacy of eltrombopag in comparison to rituximab or splenectomy in second line treatment of ITP in patients eligible for splenectomy.Methods:A subset of 84 patients treated with eltrombopag but not subject to splenectomy in the randomised, phase 3 study RAISE (PMID: 20739054) were indirectly compared with the 60 adult splenectomy candidates with ITP treated with rituximab and included in the prospective multicentre phase 2 study by Godeau et al (PMID:18463354), and a large retrospective cohort of patients (n = 233) who underwent splenectomy for ITP in the study by Vianelli et al (PMID:23144195). After controlling for covariates, we estimate that the odds of response (platelet count &gt;50 000 per μL) to eltrombopag is significantly higher than rituximab (OR = 4.6; 95%CI: 1.9 to 10.0). An adjusted response rate (platelet count &gt;30 000 per μL) of 83.3% for eltrombopag treatment in ITP was estimate relative to 73.2% for splenectomy (OR = 2.8; 95%CI: 0.7 to 11.1).Results:A subset of 84 patients treated with eltrombopag but not subject to splenectomy in the randomised, phase 3 study RAISE (PMID: 20739054) were indirectly compared with the 60 adult splenectomy candidates with ITP included in the prospective multicentre phase 2 study by Godeau et al (PMID:18463354), and a large retrospective cohort of patients (n = 233) who underwent splenectomy for ITP in the study by Vianelli et al (PMID:23144195). After controlling for covariates, we estimate that the odds of response (platelet count &gt;50 000 per μL) to eltrombopag is significantly higher than rituximab (OR = 4.6; 95%CI: 1.9 to 10.0). An adjusted response rate (platelet count &gt;30 000 per μL) of 83.3% for eltrombopag treatment in ITP was estimate relative to 73.2% for splenectomy (OR = 2.8; 95%CI: 0.7 to 11.1).Summary/Conclusion:Adjusted indirect comparisons is a useful resource for evidence‐based decision‐making when no head‐to‐head data exists between alternative treatment options. Within the limits of the available data and of the methodology, eltrombopag is estimated to be the most effective second line treatment for the management of chronic immune thrombocytopenia patients candidates to splenectomy. Head‐to‐head clinical trials are needed to support these findings.

PF707 INCIDENCE AND OUTCOMES OF REFRACTORY IMMUNE THROMBOCYTOPENIC PURPURA IN CHILDREN; A SINGLE INSTITUTION EXPERIENCE

Background:The treatment of refractory immune thrombocytopenic purpura (ITP) in children is challenging. Although various medical approaches have been used to treat refractory ITP, few data are available on the long‐term incidence of outcomes in children with refractory ITP.Aims:In this study, we aimed to reveal the outcomes of 87 children with ITP in our institution during the last 19 years.Methods:We retrospectively reviewed the clinical data of children who were newly diagnosed with ITP from April 1998 to March 2017 at the Nihon University Itabashi Hospital. Patients aged below 16 years were included in this study. Patients with follow‐up duration of less than 3 months were excluded. In this study, refractory ITP was defined as a platelet count of &lt;50 × 109 /L, which did not respond to intravenous immunoglobulin (IVIG) and prednisolone (PSL). The definition of the treatment response was as follows: complete response (CR) or partial response (PR), platelet count sustaining more than 100 × 109/L or between 50 and 100 × 109/L at 6 months after change in the treatment approach, respectively. Since 2009, we have introduced cyclosporine (CSA) for refractory ITP; we have diagnosed refractory ITP as refractory thrombocytopenia, which is a subtype of refractory cytopenia of childhood, and then we have used CSA for such patients. In this study, we compared the incidence of CR plus PR in refractory ITP at 3 years after diagnosis in the 1998–2008 group and in the 2009–2017 group. This retrospective study was approved by the institutional review board.Results:A total of 87 children with ITP were identified (50 males and 37 females): 42 children (48%) in the 1998–2008 group and 45 children (52%) in the 2009–2017 group. There were 9 patients (21%) with refractory ITP in the 1998–2008 group and 8 patients (18%) in the 2009–2017 group. Treatment chart in 17 patients with refractory ITP are shown in Figure 1. We changed the diagnosis of ITP to refractory thrombocytopenia in the all patients with refractory ITP in the 2009–2017 group, and initiated treatment with CSA. CSA was started at a dose of 4–6 mg/kg/day (per oral), and the trough level was adjusted between 100 and 150 ng/ml. Two patients achieved CR by CSA therapy alone at 16 and 119 days after starting CSA therapy, respectively. One patient achieved PR with the addition of PSL. Five patients did not respond to CSA therapy alone and then received IVIG at the CSA trough level of more than 100 ng/ml. With this approach, 4 patients achieved CR at a median time of 21 days (range, 13–38) after starting CSA therapy. Overall, 7 out of the 8 patients with refractory ITP in the 2009–2017 group maintained CR plus PR at 3 years after diagnosis. No severe CSA‐associated adverse event was seen in any patients. In contrast, only 2 out of 9 patients with refractory ITP in the 1998–2008 group achieved CR spontaneously (without additional treatment) at 3 years after diagnosis. Moreover, 2 patients obtained CR after splenectomy, and the other 5 patients remained with thrombocytopenia.Summary/Conclusion:CSA with or without IVIG therapy was effective in most cases (88%) of childhood refractory thrombocytopenia. These findings indicate that childhood thrombocytopenia is partially mediated by T cells. Although splenectomy was a conventional treatment for refractory ITP, it surely increases the long‐term risks of venous and arterial thrombosis as well as sepsis from Streptococcus pneumoniae. Therefore, CSA with or without IVIG therapy is feasible in children with refractory ITP to avoid splenectomy.image

Thrombopoietin Receptor Agonists: Can These Be the Future Answer to the Deadly Thrombocytopenia in Dengue Fever?

Dengue is considered the most prevalent mosquito-borne viral disease worldwide and sometimes turns out to be life-threatening. Thrombocytopenia is frequently observed in mild and severe cases of dengue. Severe thrombocytopenia, with a platelet count much below the normal range and hemorrhagic manifestation, is considered a fatal consequence of dengue that needs proper and timely management. The development of the dengue vaccine is quite challenging due to the existence of four different serotypes of the virus. Currently, neither a specific antiviral therapy nor a vaccine is available, and the common treatment modalities include fluid replacement therapy and platelet transfusions. Besides dengue, thrombocytopenia is correlated with many other diseases, particularly immune thrombocytopenic purpura (ITP). Thrombopoietin receptor (TPO-R) agonist, which is responsible for increasing platelet count, is a novel treatment option for chronic ITP patients. At present, two TPO-R agonists - eltrombopag and romiplostim - approved by the US Food and Drug Administration (USFDA) have been successfully used for the treatment of chronic ITP and other thrombocytopenic conditions. However, to date, only a single case study reported the use of romiplostim to enhance the platelet count in a myeloma patient suffering from dengue-associated thrombocytopenia. The objective of this review is to propose to the medical fraternity to consider using these TPO-R agonists to treat dengue hemorrhagic patients with thrombocytopenia and to conduct relevant researches to find out the usefulness of these molecules. This review is completely based on hypotheses and articles showing the positive response with romiplostim in dengue after going through a web-based search on various search engines. Furthermore, this review highlights the need for good-quality, randomized controlled trials and meta-analyses to detect the safety and efficacy of romiplostim and eltrombopag therapy for patients suffering from dengue-related thrombocytopenia.