Management Of Primary Immune Thrombocytopenia Research Articles

Management of Primary Immune Thrombocytopenia: Turkish Modified Delphi-Based Consensus Statement for Special Considerations

Primary immune thrombocytopenia (ITP) is an acquired disorder of platelets with a complex and unclear mechanism of increased immune destruction or impaired production of platelets. While the management of ITP is evolving, there is still a need for guidance, particularly in certain circumstances such as pregnancy, emergencies, or patients requiring co-medications. We aimed to determine the tendencies of hematologists in Türkiye in the event of such special considerations. Applying a modified Delphi method, the Turkish National ITP Working Group, founded under the auspices of the Turkish Society of Hematology, developed a questionnaire consisting of statements regarding pregnancy, emergencies, and circumstances requiring co-treatment with antiaggregants or anticoagulants. A total of 107 hematologists working in university or state hospitals voted for their agreement or disagreement with the statements for two sequential rounds. The participating hematologists reached an agreement on starting treatment for pregnant patients with platelets of less than 30x109/L and delivery either vaginally or by cesarean section being safe at platelet counts above 50x109/L. For emergencies and the rescue management of ITP, the panel agreed against the use of high-dose corticosteroids alone, preferring combinations with transfusions or intravenous immunoglobulin. For patients who require interventions, platelet counts of >50x109/L were regarded as safe for low-risk procedures as well as co-treatment with antiplatelets or anticoagulants. As the National ITP Study Group, we have observed the need to increase the practice guidance regarding patients with primary ITP requiring additional treatments including invasive interventions and co-treatments for coagulation. Decisions on the management of ITP during pregnancy should be individualized. There is a lack of consensus on the thresholds of platelet counts as well as co-morbidities and co-medications. This lack of consensus may be due to variations in practices.

Management of Primary Immune Thrombocytopenia in Pregnancy

(N Engl J Med. 2023;389:540–548) Immune thrombocytopenia (ITP) is an autoimmune disorder characterized by immunoglobulin G antiplatelet antibodies that lead to reduced platelet production and increased platelet clearance. It affects 1 in 3 people per 10,000 in the United States. ITP is more common in women of childbearing age, and during pregnancy, platelet counts may decrease, requiring special medical attention. Immunoglobulin G antiplatelet antibodies can also affect the fetus. The clinical variability of ITP complicates diagnosis and treatment, and uncertainty remains for many aspects of management. This article focuses on recent research on the risk assessment and management of primary ITP.

Romiplostim-Free Response in Immune Thrombocytopenia: Experience in Cuenca-Ecuador

Background: Thrombopoietin analogues (TPO) achieve overall response rates of 75-80%, and in 60% are sustained with continuous administration for 6 months. In 10-30% of patients, response is maintained despite discontinuation of these drugs. Objectives: -Evaluate the percentage of patients with Romiplostim-free response criteria: platelet count ≥50,000/µL for at least six months (twenty-four consecutive weeks) in the absence of romiplostim and any other concomitant or rescue treatment for immune thrombocytopenia. -Determine sustained response factors after discontinuation of Romiplostim Materials and methods: Retrospective, analytical study in patients older than fifteen years with immune thrombocytopenia who accessed to romiplostim. Patients with systemic lupus erythematosus were included. Data was collected from the digitized medical records of a tertiary level hospital in Cuenca (Ecuador). The nonparametric Mann-Whitney U test using SPSS version 25 software (Chicago, IL) was used to establish comparisons between potential factors that may be associated with Romiplostin-free response. Results: a) Twenty-one patients with immune thrombocytopenia received romiplostim between August 2015 and February 2023 at some point.b) The median time from ITP diagnosis was 93 months (Q1 percentiles of 51.5 and Q3 106.5) for romiplostim use.c) The median duration of treatment with Romiplostim was 61 months (Q1 percentile range 18.5 and Q3 79).d) 37.5% (n:6) met Romiplostim-free response criteria, with a median follow-up of 7 months (Q1 percentile range of 3.5 and Q3 27.1). For this analysis, five patients were excluded (three who switched to eltrombopag, one who was lost to follow-up due to the health pandemic, one who had no response).e) One patient restarted Romiplostim after twenty months of sustained response.f) 23.8% (n:5) were able to discontinue romiplostim without restarting it. Conclusion(s): 1) 37.5% achieved Romiplostim-free response criteria 2) No predictors of sustained response were found for Romiplostim discontinuation (p>0.05). Bibliography: 1. Cooper N: Tapering and Discontinuation of Thrombopoietin Receptor Agonist Therapy in Patients with Immune Thrombocytopenia: Results from a Modified Delphi Panel. Acta Haematologica. 2021; 144:418-426 2. Iino M: Treatment-free remission after thrombopoietin receptor agonist discontinuation in patients with newly diagnosed immune thrombocytopenia: an observational retrospective analysis in real-world clinical practice. International Journal of Hematology. 2020;112(2):159-168 3. Neunert C: American Society of Hematology 2019 guidelines for immune thrombocytopenia. Blood Advances. 2019; 3(23): 3829-3866 4. Provan D: Updated international consensus report on the investigation and management of primary immune thrombocytopenia. Blood Advances: 2019; 3(22): 3780-3817. 5. Zaja F: Tapering and discontinuation of thrombopoietin receptor agonists in immune thrombocytopenia: Real-world recommendations. Blood Reviews. 2020; 41: 100647

Avatrombopag Plus Fostamatinib Combination Efficacy and Safety in Patients with Immune Thrombocytopenia

INTRODUCTION Avatrombopag (AVA) is a thrombopoietin receptor agonist (TPO-RA), approved for the treatment of immune thrombocytopenia (ITP), as second line in subjects with chronic ITP unresponsive to other treatments. Global response rate of AVA is 69% with a mean duration of 12.4 weeks in its pivotal study 1. The combination of TPO-RA plus immunosuppressive/immunomodulatory drugs could optimize treatment results in ITP, addressing different pathophysiological pathways 2. Among the most widely used immunomodulatory drugs in these circumstances are steroids, azathioprine and mycophenolate. Fostamatinib (FOS) is a splenic tyrosine kinase (SYK) inhibitor. FOS blocks the cascade of signals mediated by SYK after the activation of FcγRs, reducing macrophage activity, proliferation of B lymphocytes and production of antibodies 3. We present the experience in the combined use of AVA with fostamatinib in non-responders to said TPO-RA, an experience not reported to date. METHODS Retrospective, multicenter, international, observational, non-interventional study in patients diagnosed of primary ITP who have received treatment with AVA and FOS in combination between August 2022 and June 2023. We included patients who have not reached platelets >30x10e9/L after at least two weeks of treatment with daily 40mg of AVA, and FOS was prescribed in combination in these circumstances. Epidemiological characteristics, type of ITP, previous treatments received, starting dose, response, concomitant ITP treatment and toxicity are collected. ITP definition and response criteria are based on Provan et al 4: Response (R) as platelets 30-100x10e9/L and complete response (CR) as platelets > 100x10e9/L. Data are described in percentages for the categorical variables and in medians and ranges for the quantitative ones. RESULTS In the period of time evaluated, a total of 55 patients received treatment with AVA in Spain and Norway. The Norwegian data was acquired from the Norwegian ITP registry. In 16 of 55 patients (29%), there was no response after 2 or more weeks with AVA 280 mg weekly. In 6 of these patients, FOS was combined with AVA at a dose of 280mg weekly. Table 1 describes the characteristics of the 6 patients treated with the combination. Median time from initiation of AVA to combination with FOS was 14 days (Range: 14-21 days). The overall response of the combination was 100% (1 R, 5 CR). Median time to R was 25 days and to CR 31 days. Table 2 describes the characteristics of each patient's response. With a median follow-up from the start to last follow up of treatment in combination was 212 days (Range: 45-313 days), there was no relapse. Tapering of AVA and/or FOS was attempted in 5 patients by reducing the dose of FOS in 1 patient and the dose of AVA in 4. In patients 1 and 4, AVA was stopped, but this resulted in drop in the platelets counts. CR was achieved after reintroduction AVA in combination. With regard to toxicity, in the 6 patients treated with the combination AVA plus FOS, only two adverse events were described, both non-serious. One case of headache encountered with the use of AVA, before the initiation of FOS. The other event, was WHO grade 2 liver toxicity attributed to AVA. Hypertransaminasaemia was resolved after the interruption of avatrombopag for 6 days and reduction of AVA from 140mg to 60mg weekly. CONCLUSIONS In subjects with a lack of response to thrombopoietin analogues, the combination with immunosuppressants is an alternative to consider. The combination of avatrombopag and fostamatinib has been shown to be effective and safe, although longer series are needed to support these data. Bibliography 1. Jurczak W, Chojnowski K, Mayer J, et al. Phase 3 randomised study of avatrombopag, a novel thrombopoietin receptor agonist for the treatment of chronic immune thrombocytopenia. Br J Haematol. 2018;183(3):479-490. 2. Arai Y, Jo T, Matsui H, et al. Comparison of up-front treatments for newly diagnosed immune thrombocytopenia -a systematic review and network meta-analysis. Haematologica. 2018;103(1):163-171. 3. Bussel J, Arnold DM, Grossbard E, et al. Fostamatinib for the treatment of adult persistent and chronic immune thrombocytopenia: Results of two phase 3, randomized, placebo-controlled trials. Am J Hematol. 2018;93(7):921-930. 4. Provan D, Arnold DM, Bussel JB, et al Updated international consensus report on the investigation and management of primary immune thrombocytopenia. Blood Adv. 2019;3(22):3780-3817

The Risk of Infections in Adults with Primary Immune Thrombocytopenia (ITP)

Background Immunosuppressive treatment has remained a cornerstone in the management of primary ITP (pITP) for decades. Infections are known complications to immunosuppressive therapy, but the actual risk is not well studied in ITP. We have previously shown that the overall mortality risk is increased in pITP patients and specifically that death due to infections is 1.5-2.4-fold elevated compared to the general population. In this study,we aimed at quantifying the risk of infection, including infection subtypes, in adults with pITP and matched comparators from the general population. Study design We constructed a nationwide cohort of patients ≥18 years with pITP using the Danish Civil Registration System (CRS) and the Danish National Patient Registry (DNPR). We identified ITP patients using the specific ICD-10 diagnosis registration and age-sex matched these with up to 40 comparators without ITP from the general population. We excluded prevalent ITP, non-ITP thrombocytopenic disorders, and secondary ITP defined as one or more associated diagnosis registered any time before or up to 30 days after diagnosis of ITP. The latter included ITP in combination with hematological malignancies, autoimmune disorders etc. Hospital registered infections were identified through the DNPR, prior to 1995 using ICD-8 and ICD-10 diagnoses codes thereafter. Diagnosis codes were grouped, defining the following seven types or sites of infection: respiratory, urogenital, bloodstream, gastrointestinal, tissue and musculoskeletal, central nervous system (CNS), candidiasis and other fungal infections. Date of first registration of pITP marked start of follow-up and comparators were assigned the same start date. Patients and comparators were followed to the first of following events in each of the seven subgroups: infection, emigration, death, or end of study period (31 st of December 2016). Infections occurring before start date were categorized as prevalent. We computed 1-year, 5-year, and 10-year as well as overall cumulative incidences. In addition, relative increases in risk were estimated using Cox-specific hazard (csHR) and Fine-Gray subhazard ratios (subHR) with and without equivalent time-splits, and death as competing event. Results We identified 4,030 pITP patients and 161,020 matched comparators. In the combined group of all types of infections total follow-up time was 22,075 person-years (average 5.5 years) for pITP patients and 1,118,304 person-years (average 6.9 years) for comparators. Median age was 60 years [IQR 40-74]. Previous hospital registered infections had occurred in 37% of patients and 27% of comparators. Comorbidity was more frequent among pITP patients than among comparators. The 1-year cumulative incidences in all subgroups of infections were higher in patients compared with the general population (Figure 1). For blood stream infections the 1-year cumulative incidence reached 3.36% [95% CI 2.83-3.96] in patients and 0.47% [95% CI 0.44-0.51] in comparators. The cumulative incidences for all subtypes of infections remained higher for patients than comparators throughout the study period, but differences decreased over time. During the first year adjusted csHR for infections overall was 2.82 [95%CI 2.61-3.05] and the adjusted subHR was 2.20 [95% CI 2.01-2.41]. Blood stream infections had the relative highest risk with an adjusted csHR of 6.58 [95% CI 5.46-7.92] and adjusted subHR of 2.08 [95% CI 1.71-2.54] (Figure 2). Risks of the other types of infections were also increased during first year but diminished over time in general (Figure 2). For the entire study period the overall adjusted csHR of all infections was 1.51 [95% CI 1.35-1.67] with a subHR of 1.34 [95% CI 1.20-1.49]. Blood stream infections continued having the highest risk in the period between 6 th-10 th year with a csHR of 1.40 [95% CI 1.03-1.91]. Conclusion The risk of incident infection in patients with pITP is increased compared with the general population. This risk is especially elevated within the first year after diagnosis but remains higher than the general population also in subsequent years. The risk of blood stream infection is especially high within the first year after diagnosis, but remains higher even 20 years after diagnosis. These data may help clinicians to improve management of ITP and support shared decision making with patients.

Efficacy and Safety Study of Switching from Hetrombopag or Eltrombopag to Avatrombopag in Childhood ITP

Background: Primary immune thrombocytopenia (ITP) in children is an acquired, immunologic, hemorrhagic disorder of childhood characterized by an isolated decrease in platelet count without a clear trigger. The main pathogenesis is an immune intolerance that mediates platelet immunodestruction and underproduction. The first-line treatment options for ITP are glucocorticoids and immunoglobulins, and TPO-RAs are the first choice for second-line treatment, including eltrombopag, hetrombopag, and avatrombopag and romiplostim. The 2019 International Consensus Report on the Investigation and Management of Primary Immune thrombocytopenia recommends that switching from one TPO-RA to another TPO-RA and sequential therapy in adult patients with multiple treatment failure have been shown to have positive effects on response and adverse events. However, in the treatment of childhood ITP, the experience of the conversion between TPO-RAs is insufficient. In this study, we retrospectively analyzed the treatment status of conversion of hetrombopag or eltrombopag to avatrombopag in children with ITP in our center, and explored the efficacy and safety of conversion therapy of avatrombopag. Methods: A total of 11 patients with primary ITP who switched from hetrombopag or eltrombopag to avatrombopag for any reason between May 2021 and May 2023 were included in this study. Patients were ≤15 years of age, had been treated with hetrombopag or eltrombopag for at least 4 weeks, and the interval between discontinuation of hetrombopag or eltrombopag and initiation of avatrombopag was no more than 1 month. The secondary endpoint of observation was 2 weeks after switching to avatrombopa, and the primary endpoint was 3 months after switching to avatrombopa. Observations included platelet reactions, dose of avatrombopag, tapering of other immunosuppressive agents, and treatment-related adverse events. Results: The median platelet count of patients was 30.1×10 9/L (8.4×10 9/L,89×10 9/L) before treatment with avatrombopag, 253×10 9/L (25×10 9/L,1179×10 9/L) after 2 weeks of avatrombopag（ P=0.003）, and after 3 months of avatrombopag the median platelet count was 343×10 9/L (53×10 9/L,803×10 9/L) （ P=0.008）. The platelet response rate was 90.9% after 2 weeks of treatment with avatrombopag, with a complete response rate of 63.6%, a partial response rate of 27.3%, and a no response rate of 9.1%; the platelet response rate was 100% after 3 months of treatment with avatrombopag, with a complete response rate of 88.9% and a partial response rate of 11.1%. The median onset of action was 9 (3,21) days. During the observation period, 8 of 11 patients were able to achieve avatrombopag dose reduction therapy with a median time to dose reduction of 13 days (4,86). Eight patients who were receiving concurrent immunosuppressive therapy prior to switching to avatrombopag, including six on prednisone and two on cyclosporine, were able to discontinue immunosuppressive therapy after switching to avatrombopag, with a median time to discontinuation of 18 days (12,24). The monitoring of liver and kidney functions, etc. during the observation period did not show any significant abnormality, and no thrombotic manifestations were found. Conclusion: The results of the pediatric data analysis in this study validate the potential value of switching between TPO-RAs: when one TPO-RA fails to provide sufficient efficacy, switching to another TPO-RA treatment may have a positive effect.

Recommendations for the Clinical Approach to Immune Thrombocytopenia: Spanish ITP Working Group (GEPTI).

Primary immune thrombocytopenia (ITP) is a complex autoimmune disease whose hallmark is a deregulation of cellular and humoral immunity leading to increased destruction and reduced production of platelets. The heterogeneity of presentation and clinical course hampers personalized approaches for diagnosis and management. In 2021, the Spanish ITP Group (GEPTI) of the Spanish Society of Hematology and Hemotherapy (SEHH) updated a consensus document that had been launched in 2011. The updated guidelines have been the reference for the diagnosis and management of primary ITP in Spain ever since. Nevertheless, the emergence of new tools and strategies makes it advisable to review them again. For this reason, we have updated the main recommendations appropriately. Our aim is to provide a practical tool to facilitate the integral management of all aspects of primary ITP management.

When immune thrombocytopenia gets on your nerves: β2-adrenergic receptor agonists as a potential treatment?

When immune thrombocytopenia gets on your nerves: β2-adrenergic receptor agonists as a potential treatment?

2021 Chinese consensus on the diagnosis and management of primary immune thrombocytopenia in pregnancy.

2021 Chinese consensus on the diagnosis and management of primary immune thrombocytopenia in pregnancy.

Immune thrombocytopenia in the elderly: immunosenescent and clinical diversity.

Immune thrombocytopenia in the elderly: immunosenescent and clinical diversity.

Splenectomy for Primary Immune Thrombocytopenia Revisited at the Era of Thrombopoietin Receptor Agonists: New Insights for an Old Treatment

▪IntroductionAlthough splenectomy is still considered as the most effective curative treatment for primary immune thrombocytopenia (ITP), its use has significantly declined in the last decade, especially since the emergence of thrombopoietin receptor agonist (TPO-RAs) and anti-CD20 monoclonal antibodies 1-3. The main objective of our study was to evaluate if splenectomy was still as effective in the modern era, particularly for patients who failed to respond to TPO-RAs and rituximab. One of the secondary objectives was to assess, among patients who did not respond to or relapse after splenectomy, the pattern of response to subsequent intervention with treatments used before splenectomy and particularly TPO-RAs.MethodsThis multicentre retrospective observational study involved adults who underwent surgical splenectomy for primary ITP in France from 2011 (authorization of TPO-RAs in France) to 2020. To be included in the study, patients had to fulfil the following criteria : age ³18 years, primary ITP diagnosis defined according to the usual international criteria 2. Patients with abnormal spleen histology (other than reactional lymphoid hyperplasia, white-pulp hypoplasia or red pulp hyperplasia) or yet definite secondary ITP were excluded. Response was defined according to international criteria 4. Sustained response was defined as the absence of ITP relapse at last visit. We performed univariable and multivariable logistic regression procedures to calculates the odds ratio associated with a sustained response.ResultsIn total,185 patients, 98 (53 %) women, with median age at splenectomy of 43.3 [interquartile range 27.6-64.3] years, were included in 18 French university and general hospitals from the French reference center network. Most of the patients were splenectomised at the chronic phase of ITP (n=150, 81.1%) and only two patients had undergone surgery within 3 months after ITP onset. Of note, 100 (54.1%) and 135 (73.0%) patients received TPO-RAs and/or rituximab prior to the splenectomy, respectively. The median time of follow-up after splenectomy was 39.2 months [16.5-63.0]. Overall, 144 (77.8%) of patients had an initial response and 23 patients (12.4%) relapsed during follow-up leading to an overall rate of sustained response of 65.4%, similar to the one observed in the pre-TPO-RA's era 1. Characteristics of patients according to the period during which occurred the splenectomy is available in Table 1.Among the 14 patients who failed to respond to both eltrombopag and romiplostim prior to splenectomy a sustained response after splenectomy was observed in 7 (50%). Among the 13 patients who had failed after both TPO-RAs and rituximab, we observed a sustained response in 6 (46%).In the multivariate analysis, an older age (60-75 years: OR 0,39 [0,17-0,86], p=0.02; >75 years: OR 0,28 [0,10-0,75], p=0.013) and a history of more than 4 treatment lines for ITP before splenectomy (OR 0.25 [0.08-0.66], p=0.010) were significantly associated with a lack of sustained response after splenectomy.TPO-RAs were used for 57/64 (89.1%) patients who failed to respond to splenectomy. Among them, 21 were treated with one TPO-RA (i.e. eltrombopag or romiplostim) which was previously used before splenectomy without any efficacy and a response was observed in 13 (62%) of them.ConclusionsIn conclusion, splenectomy seems to be still a relevant option for treating adult primary ITP not responding to TPO-RAs and rituximab. Patients who fail to respond or relapse after splenectomy should be re-challenged with TPO-RAs.1. Kojouri, K., Vesely, S. K., Terrell, D. R. & George, J. N. Splenectomy for adult patients with idiopathic thrombocytopenic purpura: a systematic review to assess long-term2. Provan, D. et al. Updated international consensus report on the investigation and management of primary immune thrombocytopenia. Blood Adv.3.Neunert, C. et al. American Society of Hematology 2019 guidelines for immune thrombocytopenia. Blood Adv. 3, 3829-3866 (2019).4. Rodeghiero, F. et al. Standardization of terminology, definitions and outcome criteria in immune thrombocytopenic purpura of adults and children: report from an international working group. Blood 113, 2386-2393 (2009). [Display omitted] DisclosuresTerriou: Sanofi: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding. Ebbo: Grifols: Honoraria, Membership on an entity's Board of Directors or advisory committees; Amgen: Honoraria; Novartis: Honoraria, Membership on an entity's Board of Directors or advisory committees; Octapharma: Other: Attendance Grant; Sobi: Other: Attendance Grant. Viallard: Novartis: Consultancy; Amgen: Consultancy; Grifols: Consultancy; LFB: Consultancy. Jeandel: Novartis: Membership on an entity's Board of Directors or advisory committees, Other: Support for congress; Sobi: Membership on an entity's Board of Directors or advisory committees; Amgen: Other: Support for congress; GSK: Other: Support for congress; Pharming: Other: support for congress. Michel: Amgen: Consultancy; Novartis: Consultancy; Rigel: Honoraria; UCB: Honoraria; Alexion: Honoraria; Argenx: Honoraria. Godeau: Grifols: Consultancy; Sobi: Consultancy; Amgen: Consultancy; Novartis: Consultancy. Comont: Takeda: Honoraria, Research Funding; Novartis: Honoraria, Research Funding; Bristol Myers Squibb: Honoraria, Research Funding; AstraZeneca: Honoraria, Research Funding; Abbvie: Honoraria, Research Funding.

Primary immune thrombocytopenia in very elderly patients: particularities in presentation and management: results from the prospective CARMEN-France Registry.

Data about the presentation and the management of primary immune thrombocytopenia (ITP) in very elderly patients (VEPs; aged ≥80 years) are lacking. The aim of the present study was to describe ITP in this subgroup. The data source was the prospective CARMEN-France registry. Patients included between 2013 and 2018 were selected. ITP presentation and management in VEPs was compared to elderly patients (EPs; aged 65-79 years). We assessed factors associated with bleeding at ITP onset in VEPs. Of 541 patients, 184 were included: 87 in the VEP group and 97 in the EP group. The mean age was 85·7 years in the VEP group. Comorbidities were more frequent in the VEP group (67·4% vs. 47·9%). The median platelet count at ITP onset was similar but severe bleeding tended to be more frequent in VEPs (10·3% vs. 4·1%, P = 0·1) as well as mortality. Exposure to ITP drugs, response to first-line treatment, need of second-line treatment, evolution towards persistency, occurrence of bleeding, infection and thrombosis did not differ between groups. In VEPs, factors associated to bleeding were female sex [odds ratio (OR) 4·75, 95% confidence interval (CI) 1·31-17·32] and platelet count of <20 × 109 /l (OR 10·05, 95% CI 4·83-67·39). Exposure to anticoagulants was strongly associated with severe bleeding (OR 7·61, 95% CI 1·77-32·83).

Management of primary immune thrombocytopenia. A comparison between two historical cohorts

IntroductionIn recent years, there have been changes in the management of patients with primary immune thrombocytopenia. In this study, a review is presented of the characteristics and outcomes of children with primary immune thrombocytopenia in a children’s hospital (Hospital Infantil Niño Jesús). Moreover, an analysis is made of the changes in the care of these patients diagnosed before and after 2011, when new guidelines were published by the Spanish Society of Paediatric Haematology Oncology (SEHOP). Material and methodsData from a cohort of primary immune thrombocytopenia patients followed up in this hospital have been retrospectively reviewed. The statistical package used for the analysis was SPSS Statistics 22.0 (IBM Corp., Chicago, IL, USA). ResultsA review is presented on the clinical data from 235 paediatric patients diagnosed with primary immune thrombocytopenia. It was observed that some features at diagnosis, such as age younger than five years and a previous history of infection, influenced the probability of cure. Regarding the changes in the management of patients since 2011, the steroid doses received during the first month and the first year, and the number of days corresponding to the patient’s first admission have both significantly decreased. Splenectomies were also significantly reduced. ConclusionsSince 2011, there have been changes in the medical care of our primary immune thrombocytopenia patients: they receive lower doses of steroids, they stay fewer days in the hospital, and the number of splenectomies has decreased without increasing bleeding or worsening the clinical evolution. Furthermore, it was observed that age younger than 5 years and a history of infection prior to diagnosis were related to higher chances of recovery.

Treatment, Platelet Count Pattern and Comorbidities Among Primary Immune Thrombocytopenia (ITP) Patients Seen in Routine Clinical Practice: Data from the United Kingdom Immune Thrombocytopenia (UK ITP) Registry

IntroductionPrimary ITP is an acquired bleeding disorder which is diagnosed by elimination of secondary causes of thrombocytopenia (<100 x 109/L). In a platelet depleted state, patients experience or are at risk of bleeding. Treatment responses can vary widely and treatment-associated morbidity is a key factor in management in order to reduce complications and mortality, and improve quality of life.AimThe aim of this study is to describe treatment, platelet count pattern and prevalence of certain comorbid events of patients who were diagnosed after the introduction of the ‘International consensus report on the investigation and management of primary immune thrombocytopenia’, particularly focusing on those who did not require any treatment, those who received only 1st line treatment and those who also required 2nd line treatment.MethodThe UK Adult ITP Registry recruits adult participants (n=2700, to date) nationally through a network of around 80 centres. This study was limited to participants diagnosed from 2010 who were followed up until 31st January 2015. Various statistical analysis were carried out, including meta analytical technique (using random effect modelling) for pooling multiple platelet counts [inc. 95% confidence interval (CI)] available per participant for pre- and post ITP periods in time.ResultsThis study cohort consisted of 704 participants [female 55.3%; mean & median diagnosis age 51.9 & 54.1 years (IQR 33.7, 68.4); peak diagnosis age groups 18-29 years (18.5%) & 60-69 years (17.3%); 77.7% European ancestry].One fifth (n=138) of participants did not receive any treatment and had pooled mean (PM) platelet counts of 58.7 (95% CI 46.3, 71.0) a week before and 67.2 (95% CI 60.7, 73.8) a week after ITP diagnosis. Forty one percent (n=292) had a 1st line treatment (steroids, IVIg and/or anti-D) only whereas 35.5% needed to be given a 2nd line treatment too (rituximab 50.2%, azathioprine 39%, mycophenolate 37.5%, romiplostim 32,7%, eltrombopag 21.1%, splenectomy 13.2%, others <5%). Distribution of 1st line treatment for the former and latter sub cohorts were: prednisolone 88.0% vs. 92.8%, IVIg 28.8% vs. 65.7% and, anti-D 1.0% vs. 5.6%The historical PM platelet counts (over 14 days before ITP diagnosis) were non-significantly higher for those who required only 1st line treatment [131.1 (95% CI 114.6, 147.6)] when compared against those who required 1st and 2nd line treatment [104.6 (95% CI 85.7, 123.4)]. A week before diagnosis, PM platelet counts were not dissimilar 31.1 (95% CI 24.8, 37.4) vs. 31.8 (95% CI 16.4, 47.3)] but within the first week of treatment 59.6 (95% CI 45.1, 74.1) vs. [45.9 (95% CI 36.7, 55.1)], 1 month [138.1 (95% CI 120.6, 155.6 vs. 70.1 (95% CI 60.7, 79.4)], and up to 3 months after [157.0 (95% CI 142.9, 171.1) vs. 98.9 (95% 86.5, 111.3)] platelet count response seemed to be better during the 3 months for those who only received 1st line compared against those who went on to receive 2nd line treatment.There were more females in the ‘1st line treatment only ‘cohort (58%, p<0.001). No gender differences were found among those who did not require any treatment or those who ended up having 2nd line treatment. There was no dissimilarity in age at diagnosis or distribution of comorbidities among these sub cohorts.ConclusionThis study was beneficial in identifying pertinent patterns for more in-depth analysis and interpretation. A third of participants were found to require a second line treatment at some point after their diagnoses. Since 2010, splenectomy still remained a treatment choice whereas romiplostim and eltrombopag are utilised by 20 to 30% of the cohort. Participants who ended up having a second line treatment tended to have a lower platelet count profile before and within 3 months of ITP diagnosis; this later period usually coincided with 1st line therapeutic intervention. Whether this is predictive of their poor responses and requiring 2nd line treatment will be analysed further while considering other pertinent characteristics. However, a larger cohort is needed to fully assess effects of different treatments on outcomes and morbidity, through wider collaboration. [Display omitted] DisclosuresDoobaree:GSK: Research Funding; GSK: Consultancy; Amgen: Research Funding; ITP Support Association: Other: donation to theUKITP Registry. Nandigam:GSK: Other: Research funding to the Registry, Research Funding; Amgen: Other: Research funding to the Registry, Research Funding; ITP Support Association: Other: donation to the UKITP Registry, Research Funding. Newland:Amgen Inc.: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau; Angle: Consultancy; Argenx: Consultancy, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Rigel: Consultancy; Shionogi: Consultancy; Novartis: Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau; GSK: Research Funding. Provan:GSK: Consultancy, Other: shares, Research Funding; Novartis: Consultancy, Research Funding; Shanogi: Consultancy; ONO: Consultancy; Eisa: Consultancy; Baxter: Consultancy; UCB: Consultancy; BMS: Consultancy.

Management of primary immune thrombocytopenia in a real-world setting in Japan: eltrombopag versus corticosteroids.

This real-world study in Japan assessed the long-term safety of persistent use of eltrombopag compared to corticosteroids. Overall, 1887 patients with primary immune thrombocytopenia were included in the study cohort, based on hospital claims data. Eltrombopag was frequently used as a second- or third-line therapy (monotherapy: 13.1% and 25.7%; combination: 24.39% and 16.52%, respectively). The risk of bleeding was approximately 30% lower in the eltrombopag group (as monotherapy and in combination with other drugs including corticosteroids) than the corticosteroid group (hazard ratio, 0.66; 95% confidence interval, 0.45-0.96). Results from univariate and multivariate Cox models indicated that patients aged ≥ 60years, male patients and patients who received the drugs for peptic ulcer or gastroesophageal reflux disease have a higher risk of cerebral haemorrhage or gastrointestinal bleeding. Surgeries were more common among patients on corticosteroids compared to patients on eltrombopag (39.1% vs 34.6%, P = 0.004), while splenectomies were very rare. There was no significant difference in the costs of scheduled, emergency, or any type of hospitalisations between the exposure groups. The risk of infections, cataracts, and thrombosis did not differ between the exposure groups.

Evidence-based clinical practice guideline for the management of primary immune thrombocytopenia (ITP) in pediatric population

Introduction: Primary immune thrombocytopenia (ITP) is the most common cause of thrombocytopenia in children, with a reported incidence of 1.1-12.5 cases per 100 000 children. However, currently, there are several definitions of ITP, as well as diagnostic and therapeutic approaches. Objective: To develop an evidence-based clinical practice guideline (CPG) to standardize the definition of ITP and, in this way, reduce the variability of its diagnosis, and to provide indications for the treatment of acute, persistent, and chronic ITP in patients under 18 years of age. Materials and methods: The CPG was prepared by a multidisciplinary group that followed the Grading of Recommendations, Assessment, Development and Evaluations (GRADE) guidelines for developing CPGs, formulated PICO clinical questions, and conducted systematic reviews. GRADE evidence profiles were created and recommendations, with their corresponding level of evidence and strength, were made after a panel of experts assessed the benefit-risk balance, the quality of evidence, the patients’ values and preferences, and the context in which they should be implemented. Results: A total of 23 recommendations were made to pediatricians, hematologists, and health professionals working in emergency services for treating acute, persistent, and chronic ITP. Overall, the CPG has low quality of evidence, and the recommendations were made in order to improve the success rate of ITP treatment and the prognosis of children with this condition. Conclusions: Although ITP is the main cause of thrombocytopenia in pediatrics, to date there is not enough high-quality evidence that supports the recommendations presented here for its proper classification and treatment in children. Thus, further studies providing high-quality evidence on this issue are required.

Looking long-term: an unmet need in immune thrombocytopenia

Immune thrombocytopenia is a rare condition in which patients develop autoimmune platelet destruction coupled with impaired platelet production. This results in severe thrombocytopenia and places patients at risk for haemorrhage. Standard first-line treatment for adults with immune thrombocytopenia is corticosteroids, with either prednisone or dexamethasone. 1 Neunert C Terrell DR Arnold DM et al. American Society of Hematology 2019 guidelines for immune thrombocytopenia. Blood Adv. 2019; 3: 3829-3866 Crossref PubMed Scopus (334) Google Scholar , 2 Provan D Arnold DM Bussel JB et al. Updated international consensus report on the investigation and management of primary immune thrombocytopenia. Blood Adv. 2019; 3: 3780-3817 Crossref PubMed Scopus (282) Google Scholar Although this approach is efficacious, most patients are unable to maintain a sustained response and will relapse once medication is discontinued. 3 Cuker A Prak ET Cines DB Can immune thrombocytopenia be cured with medical therapy?. Semin Thromb Hemost. 2015; 41: 395-404 Crossref PubMed Scopus (45) Google Scholar For this reason, alternative approaches have been explored by use of upfront combination therapy in order to provide improved long-term outcomes. In this issue of The Lancet Haematology, authors Lu Sun and colleagues 4 Sun L Wang J Shao L et al. Dexamethasone plus oseltamivir versus dexamethasone in treatment-naive primary immune thrombocytopenia: a multicentre, randomised, open-label, phase 2 trial. Lancet Haematol. 2021; 8: e289-e298 Summary Full Text Full Text PDF Scopus (9) Google Scholar report results on use of combination dexamethasone and oseltamivir for patients with treatment-naive immune thrombocytopenia. Dexamethasone plus oseltamivir versus dexamethasone in treatment-naive primary immune thrombocytopenia: a multicentre, randomised, open-label, phase 2 trialDexamethasone plus oseltamivir offers a readily available combination therapy in the management of newly diagnosed primary immune thrombocytopenia. The preliminary activity of this combination warrants further investigation. Multiple cycles of oseltamivir, as a modification of current first-line treatment, might be more effective in maintaining the platelet response. Full-Text PDF

New Developments in the Pathophysiology and Management of Primary Immune Thrombocytopenia.

Immune thrombocytopenia (ITP) is an autoimmune disease that is characterized by a significant reduction in the number of circulating platelets and frequently associated with bleeding. Although the pathogenesis of ITP is still not completely elucidated, it is largely recognized that the low platelet count observed in ITP patients is due to multiple alterations of the immune system leading to increased platelet destruction as well as impaired thrombopoiesis. The clinical manifestations and patients' response to different treatments are very heterogeneous suggesting that ITP is a group of disorders sharing common characteristics, namely, loss of immune tolerance toward platelet (and megakaryocyte) antigens and dysfunctional primary hemostasis. Management of ITP is challenging and requires intensive communication between patients and caregivers. The decision to initiate treatment should be based on the platelet count level, age of the patient, bleeding manifestation, and other factors that influence the bleeding risk in individual patients. In this review, we present recent data on the mechanisms that lead to platelet destruction in ITP with a particular focus on current findings concerning alterations of thrombopoiesis. In addition, we give an insight into the efficacy and safety of current therapies and management of ITP bleeding emergencies.

Frontiers in the Management of Primary Immune Thrombocytopenia (ITP)

Frontiers in the Management of Primary Immune Thrombocytopenia (ITP)

Результаты лечения высокогорным климатом иммунной тромбоцитопении у детей в Кыргызской Республике (пятилетний анализ)

Введение: Вопрос о дальнейшем совершенствовании базисной терапии иммунной тромбоцитопении (ИТП) по-прежнему широко обсуждается специалистами и является предметом оживленных дискуссий. Цель исследования: оценить эффективность высокогорной климатотерапии при хронической ИТП у детей за 5-летний период наблюдения после ежегодного лечения на высокогорной базе. Материалы и методы: В исследование включено 22 ребенка с хронической ИТП в возрасте от 3 до 14 лет, средний возраст — 6,30 ± 1,02 года, длительность заболевания 2-8 лет. Для лечения детей поднимали на высокогорную базу. Продолжительность лечения в высокогорье составляла 40 дней. Результаты: Из 22 детей, получивших 5 курсов высокогорной климатотерапии, у двоих наблюдали полную ремиссию в виде увеличения тромбоцитов более 100×109/л без кровоточивости. Объективный ответ в виде двукратного увеличения числа тромбоцитов, но менее 100×109/л без кровоточивости установлен у 18 детей, отсутствие эффекта было зарегистрировано у 2 детей. Заключение: Повторные курсы высокогорной климатотерапии способствуют улучшению клинической картины, существенному повышению числа тромбоцитов в периферической крови и достижению ремиссии при ИТП у детей. Background: Further development of basic treatment of immune thrombocytopenia (ITP) is still widely discussed by specialists and is the subject of lively discussions. Objectives: to assess the effi ciency of high-altitude climatotherapy in children with chronic ITP for a 5-year follow-up period after annual treatment at high-altitude base. Patients/Methods: The study included 22 children with chronic ITP from 3 to 14 years, the average age was 6.30 ± 1.02 years, and disease duration was 3-8 years. Children were raised to high-altitude base. Treatment duration was 40 days. Results: 22 children received 5 courses of high-altitude climatotherapy. Complete remission was observed in 2 patients with increasing of platelets more than 100×109/L without bleeding. In 18 children an objective response was found in the form of twofold increasing of platelets number, but less than 100×109/L without bleeding; no effect was recorded in 2 children. Conclusions: Repeated courses of high-altitude climatotherapy improve clinical characteristics, significantly increase the number of platelets in the peripheral blood and contribute to remission in children with ITP.