Adult Immune Thrombocytopenia Research Articles

Bleeding risk assessment in immune thrombocytopenia.

The bleeding risk in immune thrombocytopenia (ITP) is related not only to low platelet count but also to the presence of platelet dysfunction. However, diagnosing a concomitant platelet dysfunction is challenging as most of the available platelet function assays (PFAs) require a platelet count of greater than 100,000/μL. Sonoclot coagulation and platelet function analyzer works on the principle of viscoelastometry, and results remain unaffected by the platelet counts. To assess the platelet function in adult acute ITP patients with the help of sonoclot coagulation and platelet function analyzer and correlate it with the risk of bleeding. Newly diagnosed acute ITP patients with a platelet count less than 20,000/μL were divided into two groups based on WHO bleeding grade: ITP non-bleeder (ITP-NB) group (WHO bleeding grade ≤1) and ITP bleeder (ITP-B) group (WHO bleeding grade ≥2). Platelet function was assessed by sonoclot in both groups. The patients without significant bleeding (ITP-NB) were followed up monthly for six months with the assessment of platelet function during each contact. Eighty patients (30 ITP-B and 50 ITP-NB) were prospectively included in this study. The median age of patients in the two groups was 37 years and 30 years, respectively. The female-to-male ratio was 4:1 and 1:1 in ITP-B and ITP-NB groups. The median platelet count in ITP-B and ITP-NB was 12000/μL (range 1000-19000/μL) and 8000/μL (range 1000-19000/μL), respectively. Mean platelet functions by sonoclot in both groups were lower than the normal cut-off (>1.6). However, the mean platelet function in the ITP-B group (0.2 + 0.17) was significantly lower than the ITP-NB group (1.2 ± 0.52) (p = 0.01). During the follow-up period of 6 months, patients in ITP-NB with a normal platelet function (>1.6) on sonoclot had lesser episodes (one episode) of clinically significant bleeding than patients with a low platelet function (4 episodes). Patients with acute severe thrombocytopenia and bleeding phenotype have a greater abnormality on platelet function by sonoclot than patients with non-bleeding phenotype. This information may help in taking therapeutic decisions in patients with acute ITP.

Is splenectomy a good strategy for refractory immune thrombocytopenia in adults?

Rituximab and thrombopoietin receptor agonists (TPO-RAs) have profoundly changed the management of immune thrombocytopenia (ITP) over the last 20 years. Even if most current guidelines put splenectomy, rituximab and TPO-RAs on the same treatment level, most clinicians and patients clearly prefer to postpone splenectomy and to multiply the lines of medical treatment before considering surgery. The management of ITP refractory to rituximab and TPO-RAs is challenging. Splenectomy is currently performed much less frequently because of a better knowledge of its complications, particularly severe late infections and deep vein thrombosis, and the inability to reliably predict its effectiveness. Furthermore, there is a reluctance to propose splenectomy when other treatments have been ineffective, based on the not well-documented risk that splenectomy could not be effective in such a case. The objective of this update was to review the most recent published data on the long-term tolerability and side effects of splenectomy and the predictors of response and efficacy, especially for patients exposed to multiple medical lines. This update can help physicians and patients with failure of multiple lines of therapy make an informed decision on the indication for splenectomy with the help of up-to-date data.

Relationships of platelet glycoprotein specific antibody with therapeutic efficacy of short-term high-dose dexamethasone and bleeding score in the newly diagnosed adult patients with primary immune thrombocytopenia

ABSTRACTObjectives: We aimed to investigate relationships of platelet glycoprotein (GP) specific antibody with therapeutic efficacy of high-dose dexamethasone (HD-DXM) and bleeding score in primary immune thrombocytopenia (ITP) adults. Methods: A retrospective study was carried out to analyze relationships of polymorphism of GP specific antibody with initial therapeutic efficacy of HD-DXM and bleeding score of newly diagnosed ITP adults between 1 June, 2016 and 31 January, 2020. Results: 59 patients were involved in the study, with 33 cases of responders and 26 cases of non-responders between June 2016 and January 2020. At admission, there were 31 (52.5%) GP antibody-positive patients. Initial therapy of HD-DXM was effective for 78.6% GP antibody-negative patients and 35.5% GP antibody-positive patients, with a better therapeutic efficacy in patients with anti-GP Ib/IX antibody or anti-GP IIb/IIIa antibody but not in those with anti-GP Ib/IX antibody plus anti-GP IIb/IIIa antibody. Notably, therapeutic efficacy is much worse for minority (Uyghur) patients compared with corresponding Han patients. Similarly, it was much lower in GP antibody-positive patients compared with corresponding negative ones at low and medium bleeding score, with no response in GP antibody-positive patients at high bleeding score. Furthermore, there was a moderate negative correlation between therapeutic efficacy and GP-specific antibody (p < 0.05), but no obvious linear relationship between clinical bleeding degree and GP-specific antibody (p > 0.05). Conclusion: Collectively, the newly diagnosed ITP adults with GP-specific antibody have a poor response to short-term HD-DXM, especially in minority (Uyghur) patients with GP-specific antibody in China.

Refractory immune thrombocytopenia in adults: Towards a new definition.

Immune thrombocytopenia (ITP) is an autoimmune haematological disorder characterized by immune-mediated thrombocytopenia and a variable risk of bleeding. Despite the availability of multiple treatment options, some patients are considered refractory since they do not achieve a platelet count response to multiple treatments and are at risk of bleeding. The term 'refractory' has been used to identify this patient group; however, with the advent of multiple lines of treatment, its meaning has become ambiguous. To address this issue, we reviewed previous definitions of refractory ITP, solicited the views of ITP experts and collected data from registries to inform a definition. Twenty ITP experts who attended the 7th Expert Meeting of the Intercontinental Cooperative ITP Study Group in September 2022 answered a web-based survey: 95% felt that there was a need for a new definition of refractory ITP for clinical and research purposes. The use of the term refractory, accompanied by a clear indication of the type and timing of failed treatments, was supported by 85% of respondents. Preliminary data on the frequency of refractory patients from the McMaster and Norwegian ITP Registries demonstrated that the proportion of adult ITP patients who had failed first-line therapy, rituximab, thrombopoietin receptor agonists, any immune suppressant medication and splenectomy ranged from 0.4% to 3.8%. We propose a definition of refractory ITP that could be evaluated in future studies.

Avatrombopag for adult chronic primary immune thrombocytopenia: a randomized phase 3 trial in China

BackgroundImmune thrombocytopenia (ITP) is an autoimmune disorder with decreased platelet counts and increased bleeding risk. ObjectivesTo evaluate the efficacy and safety of avatrombopag, a second-generation oral thrombopoietin receptor agonist, for the treatment of Chinese patients with chronic primary ITP. MethodsThis multicenter, randomized, double-blind, placebo-controlled phase 3 study (CTR20210431) consisted of a 6-week double-blind core treatment phase followed by a 20-week, open-label extension phase. Chinese adults with chronic primary ITP for at least 12 months and a platelet count <30 × 109/L were randomized (2:1) to receive avatrombopag (initial dose of 20 mg/day) or matched placebo. The primary endpoint was the proportion of subjects with a platelet count ≥50 × 109/L at week 6 of the core treatment phase in absence of rescue therapy. ResultsIn total, 74 patients were randomized (avatrombopag: N = 48; placebo: N = 26) between March 5, 2021, and August 6, 2021; all of whom entered the extension phase (72 received avatrombopag up to 26 weeks). At week 6 of the core study, the platelet response (≥50 x 109/L) rate was significantly higher in the avatrombopag group (77.1%; 95% CI, 62.7, 88.0) vs placebo (7.7%; 95% CI, 1.0, 25.1); the treatment difference was 69.4% (95% CI, 56.2, 86.3; P < .0001). During the 6-week core study, treatment-emergent adverse events were reported in 41 (85.4%) and 20 (76.9%) patients in the avatrombopag and placebo groups, respectively. The most common avatrombopag-related treatment-emergent adverse events were upper respiratory tract infection (14/48 [29.2%]), increased platelet count (13/48 [27.1%]) and headache (7/48 [14.6%]). ConclusionAvatrombopag was efficacious and generally well tolerated in Chinese patients with chronic primary ITP, with comparable efficacy and safety to previous reports in Western patients.

Deciphering the genetic basis of immune thrombocytopenia: current evidence for genetic predisposition in adult ITP.

Immune thrombocytopenia (ITP) is the consequence of a complex, still incompletely understood immunological dysregulation. Proposed mechanisms include autoantibody-induced platelet destruction, impaired platelet production as well as abnormalities in T-cell immunity, such as T helper cells (Th1) polarization, a high proportion of Th17 cells, and a reduced number of regulatory T cells. Although the etiology of ITP is incompletely understood and considered multifactorial in most cases, genetic variants are thought to play a key role in susceptibility to ITP, especially in persistent or chronic ITP. Efforts are currently underway to uncover possible predisposing genetic factors for the development of ITP. Single-nucleotide polymorphisms and copy number variations have been identified in several immune-related genes, such as cytokine genes, Fcγ receptor genes or T-cell costimulation genes, and have been associated with patients' susceptibility to ITP. However, because of the clinical heterogeneity and low incidence of ITP it remains challenging to perform genetic analyses with sufficiently large sample size within informative patient populations, highlighting the need for collection of well-annotated biomaterials in clinical trials or registry projects. Another significant challenge is to go beyond performing association studies alone and to establish genotype-phenotype associations, thus proving causality between a genetic alteration and ITP pathogenesis. This review summarizes our current knowledge on genetic alterations identified as potential predisposing factors for the development of ITP in adults, thereby addressing signaling pathways considered critical for ITP pathogenesis.

Immune thrombocytopenia in adults: Epidemiology, clinical course, prognostic factors in two third level institutions of Antioquia, 2012–2018: Cohort follow-up study

IntroductionPrimary immune thrombocytopenia (pITP) is a hematological disorder characterized by the destruction of platelets by an immunological phenomenon. The main therapeutic objective is the rapid and sustained increase in platelet count to reduce the risk of bleeding. There are discrepancies between the prognostic factors in children and adult patients. ObjectiveTo determine the prognostic factors (clinical, laboratory, sociodemographic) for the development of chronic and persistent pITP in adults in two institutions of the Department of Antioquia 2012–2018. Materials and methodsObservational, analytical study, longitudinal design based on information obtained from a cohort of patients. Bivariate and multivariate analysis techniques (logistic regression) are used to study predictors and model development. ResultsChronic persistent pITP corresponds to 65% of patients, predominantly women (82%). There is an association with chronicity between the variables of symptom times greater than 15 days (OR: 5.45; 95% CI: 2.3–12.5), dexamethasone treatment (OR: 0.074; 95% CI: 0.023–0.23), prednisolone treatment (OR: 0.35; 95% CI: 0.125–1.034). A predictive model was developed, including variables: time of symptoms and treatment (sensitivity of 87.5%, specificity of 52.94%, PPV 78%, NPV 69%), and 3 risk groups were estimated. ConclusionsThere are clinical and paraclinical factors that can predict the risk of chronicity for pITP in the adult population; these findings must be confirmed by prospective studies and external validation of the multivariate model proposed in the present investigation.

Genome-wide DNA methylation profiling of CD4+ T lymphocytes identifies differentially methylated loci associated with adult primary refractory immune thrombocytopenia

BackgroundDNA methylation played a crucial role in the pathogenesis of immune thrombocytopenia (ITP). However, genome-wide DNA methylation analysis has not been applied thus far. The present study aimed to provide the first DNA methylation profiling for ITP.MethodsPeripheral blood CD4+ T lymphocytes samples were collected from 4 primary refractory ITP cases and 4 age-matched healthy controls, and DNA methylome profiling was performed using Infinium MethylationEPIC BeadChip. Differentially methylated CpG sites were further validated in another independent cohort of 10 ITP patients and 10 healthy controls using qRT-PCR.ResultsThe DNA methylome profiling identified a total of 260 differentially methylated CpG sites mapping to 72 hypermethylated and 64 hypomethylated genes. These genes were mainly enriched in the actin nucleation of the Arp2/3 complex, vesicle transport, histone H3-K36 demethylation, Th1 and Th2 cell differentiation, and Notch signaling pathway according to the GO and KEGG databases. The mRNA expression of CASP9, C1orf109, and AMD1 were significantly different.ConclusionsGiven the altered DNA methylation profiling of ITP, our study provides new insights into its genetic mechanism and suggests candidate biomarkers for the diagnosis and treatment of ITP.

Efficacy and Safety Analysis of Combination Therapy Consisting of Intravenous Immunoglobulin and Corticosteroids versus Respective Monotherapies in the Treatment of Relapsed ITP in Adults.

Objective In this study, we aimed to evaluate the efficacy and safety of combination therapy, consisting of intravenous immunoglobulin (IVIg) and corticosteroids, in comparison to respective monotherapies in the treatment of relapsed immune thrombocytopenia (ITP) in adults. Methods A retrospective analysis of clinical data was conducted on 205 adult patients with relapsed ITP who received first-line combination therapy or monotherapy in multiple centers across China from January 2010 to December 2022. The study evaluated the patients' clinical characteristics, efficacy, and safety. Results We found that the proportion of patients with platelet counts in complete response was significantly higher in the combination group (71.83%) compared with the IVIg group (43.48%) and the corticosteroids group (23.08%). The mean PLT max in the combination group (178 × 10 9 /L) was significantly higher than that in the IVIg group (109 × 10 9 /L) and the corticosteroids group (76 × 10 9 /L). Additionally, the average time for platelet counts to reach 30 × 10 9 /L, 50 × 10 9 /L, and 100 × 10 9 /L in the combination group was significantly shorter than in the monotherapy groups. The proportion curves for reaching these platelet counts during treatment were also significantly different from those in the monotherapy groups. However, there were no significant differences in the effective rate, clinical characteristics, and adverse events among the three groups. Conclusion We concluded that combining IVIg and corticosteroids was a more effective and faster treatment for relapsed ITP in adults than using either therapy alone. The findings of this study provided clinical evidence and reference for the use of first-line combination therapy in the treatment of relapsed ITP in adults.

Romiplostim in primary immune thrombocytopenia that is persistent or chronic: phase III multicenter, randomized, placebo-controlled clinical trial in China

BackgroundMultiple trials have confirmed that romiplostim could increase platelet count in individuals with primary immune thrombocytopenia (ITP), but no related study has assessed Chinese patients. ObjectivesTo assess the effectiveness of romiplostim as a second-line treatment of persistent or chronic ITP in Chinese adults. MethodsThis phase III multicenter, randomized, placebo-controlled, double-blind, then open-label clinical trial (NCT02868099, CTR20150395) was conducted at 28 investigational sites in China. The patients were randomly assigned (3:1) to romiplostim (starting and maximum doses of 1 and 10 μg/kg, respectively) or placebo for 9 weeks (double-blind period), followed by the open-label period (both groups administered romiplostim) to week 22. The primary endpoint was the time (in weeks) during which platelet counts were ≥50 × 109/L in the double-blind period. ResultsIn this study, 202 patients (romiplostim, n = 151; placebo, n = 51) started the treatment. The median (range) numbers of weeks with platelet response after 6 weeks of treatment were 2 (0-6) and 0 (0-2) in patients administered romiplostim and placebo, respectively (P < .001). During the double-blind period, the proportions of patients with treatment-emergent adverse events were comparable between the romiplostim and placebo groups (82.8% vs 82.4%). The treatment-emergent adverse event with ≥10% difference in incidence between these 2 groups was injection site bleeding (1.3% vs 11.8%). ConclusionRomiplostim significantly increased the time with maintained platelet response in patients with persistent or chronic ITP in comparison with placebo. No new safety signal was observed. Trial registrationClinicalTrials.gov, NCT02868099. www.chinadrugtrials.org.cn/clinicaltrials.searchlist.dhtml, CTR20150395

Current Concepts in the Diagnosis and Management of Adult Primary Immune Thrombocytopenia: Our Personal View.

Primary immune thrombocytopenia (ITP) is an acquired blood disorder that causes a reduction in circulating platelets with the potential for bleeding. The incidence of ITP is slightly higher in adults and affects more women than men until 60 years, when males are more affected. Despite advances in basic science, primary ITP remains a diagnosis of exclusion. The disease is heterogeneous in its clinical behavior and response to treatment. This reflects the complex underlying pathophysiology, which remains ill-understood. Platelet destruction plays a role in thrombocytopenia, but underproduction is also a major contributing factor. Active ITP is a proinflammatory autoimmune disease involving abnormalities within the T and B regulatory cell compartments, along with several other immunological abnormalities. Over the last several years, there has been a shift from using immunosuppressive therapies for ITP towards approved treatments, such as thrombopoietin receptor agonists. The recent COVID-19 pandemic has hastened this management shift, with thrombopoietin receptor agonists becoming the predominant second-line treatment. A greater understanding of the underlying mechanisms has led to the development of several targeted therapies, some of which have been approved, with others still undergoing clinical development. Here we outline our view of the disease, including our opinion about the major diagnostic and therapeutic challenges. We also discuss our management of adult ITP and our placement of the various available therapies.

Geographic disparities in the care and outcomes in adult chronic immune thrombocytopenia

IntroductionDespite expert-based recommendations, real-world adherence to immune thrombocytopenia (ITP) guidelines is unclear. The impact of geographic and socioeconomic disparities on the quality of care and outcomes is unknown. We sought to determine the association between geographic remoteness and material deprivation on ITP care and outcomes. MethodsWe conducted a multi-centre retrospective cohort study of adults with chronic ITP requiring a second-line therapy between 2012 and 2019 in the province of Alberta, Canada. Socioeconomic status was measured using the Pampalon material deprivation index quintiles. Geographic disparities were assessed by the driving distance to a major centre, with geographic remoteness defined as >200 km from major centre. We examined the impact of geographic and material deprivation on quality of care, resource utilization (hospitalizations, transfusions), and outcomes (major bleeding, all-cause mortality and ITP-related mortality). Cox proportional hazards models were used to examine the impact of geographic remoteness, rural residence and material deprivation on overall survival and ITP-related survival. ResultsWe included 326 ITP patients, median age of ITP diagnosis was 57 years, 182 (56 %) were female. Most patients (58 %) lived within 20 km of a major centre, whereas 49 (15 %) lived in a geographically remote area (>200 km). Geographic remoteness was significantly associated with material deprivation and lower likelihood of management by hematologists (84 % vs 99 %, P = 0.0001). It was also associated with lower rates of hepatitis C (71 % vs 89 %, P = 0.005) and hepatitis B testing (69 % vs 86 %, P = 0.03), and a non-significant trend towards lower rates of HIV testing (73 % vs 83 %, P = 0.051) compared with those <20 km from a major centre. Incomplete hyposplenic vaccinations among splenectomized patients (52 %), early splenectomy within 12 months of ITP diagnosis (35 %), inappropriate platelet transfusions (41 %), and inappropriate hospitalizations for asymptomatic thrombocytopenia (16 %) were common regardless of geographic distribution. There were 28 (9 %) ITP-related deaths (major bleeding or infections), most occurred within the first year of ITP diagnosis. Material deprivation, but not geographic remoteness, was an independent predictor of all-cause mortality (aHR 1.9, 95 % CI 1.1–3.3 in the most deprived quintile vs least deprived quintile). Rural residence trended towards increased hazard of ITP-related deaths (aHR 1.7, 95 % CI 0.9–3.2). ConclusionWe demonstrated substantial deviations of ITP care from consensus guidelines, and geographic disparities in access to care and diagnostic workup. Future quality improvement initiatives are critical to improve the quality of care and reduce inequities.

Expression and prognostic value of C-reactive protein in adult immune thrombocytopenia (ITP) patients.

The aim of this study was to investigate the effect of C-reactive protein (CRP) on the prognosis of adult patients with Immune thrombocytopenia purpura (ITP). A retrospective study of 628 adult ITP patients, as well as 100 healthy and 100 infected patients, attending the Affiliated Hospital of Xuzhou Medical University from January 2017 to June 2022 was performed. The ITP patients were grouped according to their CRP levels, and the differences in clinical characteristics of each group and the influencing factors of efficacy in newly diagnosed ITP patients were analyzed. CRP levels were significantly higher in the ITP and infected groups compared with healthy controls (P < 0.001), and platelet counts were significantly lower in the ITP group (P < 0.001). Between the CRP normal and elevated group, their age, white blood cell count, neutrophil count, lymphocyte count, red blood cell count, hemoglobin, platelet count, complement C3 and C4, PAIgG, bleeding score, proportion of severe ITP, and proportion of refractory ITP were significantly different (P < 0.05). Patients of severe ITP (P < 0.001), refractory ITP (P = 0.002), and with active bleeding (P < 0.001) had significantly higher CRP levels. Patients with no response after treatment had significantly higher CRP levels than those who achieved CR or R (P < 0.001). Platelet counts (r = - 0.261, P < 0.001) in newly diagnosed ITP patients and treatment outcomes (r = - 0.221, P < 0.001) were negatively correlated with CRP levels, and bleeding score was positively correlated with CRP levels (r = 0.207, P < 0.001). Treatment outcome was positively correlated with decrease in CRP levels (r = 0.313, P = 0.027). A multifactorial regression analysis of the influencing factors of treatment outcomes on newly diagnosed patients found that CRP was an independent risk factor of the prognosis (P = 0.011). In conclusion, CRP can help assess the severity and predict the prognosis of ITP patients.

Secondary spleen in immune thrombocytopenia: Not so accessory after all….

Immune thrombocytopenia (ITP) is an autoimmune bleeding disorder characterized by an isolated thrombocytopenia. The pathophysiology is complex but involves platelet-autoantibodies and/or cytotoxic T cells, with the spleen playing an important regulatory role. Accessory spleen (AcS) may possibly contribute to ITP relapse following splenectomy; however, the microenvironment of AcS has not been directly compared to the main spleen. Pizzi et al. conducted a histological study of adult ITP patients where they compared eight matched AcS to main spleens, and they observed a similar immunological composition in both groups. This supports the possibility of AcS-mediated ITP relapse post splenectomy. Commentary on: Pizzi et al. Accessory spleens recapitulate the immune microenvironment of the main spleen in immune thrombocytopenia. Br J Haematol 2023;202:147-152.

Recommendations of the Czech Society of Haematology for the diagnosis and treatment of immune thrombocytopenia in adults

Recommendations of the Czech Society of Haematology for the diagnosis and treatment of immune thrombocytopenia in adults

Identification factors to adjust early combination regimens in adult primary immune thrombocytopenia: An 8-year data analysis

PurposeRecent studies suggested that adding other agents to corticosteroids as a first-line treatment for immune thrombocytopenia (ITP) could improve outcomes. However, combination regimens may increase side effects and costs. To determine clinical factors associated with responses to the first-line steroid at 1 month.Materials and methodsWe retrospectively reviewed the medical records of patients with ITP aged ≥ 18 years, who were treated at Rajavithi Hospital between 2012 and 2020. Clinical data, laboratory results, treatment regimens, and responses to therapy were analyzed.ResultsOf the 226 patients, 76.6% were female. The mean age was 46.5 ± 18.1 years, and the median follow-up duration was 40 months. The proportion of chronic ITP was 97.3%. The complete response and response rates to first-line therapy were 65.5% and 88.9%, respectively. The age over 26 years, presentation clinically non-significant bleeding and a difference in platelet count of &amp;gt;50 x 109/L between days 1 and 7 after initial treatment were associated with the response to first-line treatment (adjusted odds ratio [OR] 5.09, 95% confidence interval [CI] 1.50-17.28, p = 0.009); OR 5.87, 95%CI 1.19-28.91, p = 0.029, and OR 3.60, 95%CI 1.10-11.73, p = 0.034, respectively. Younger patients and a difference in platelet count between day 1 and 7 ≤ 50 x 109/L were more likely to require second-line treatments. There were significant increases in the median platelet counts after prescribing azathioprine (baseline vs. 3 months, p = 0.001), cyclophosphamide (baseline vs. 6 months, p = 0.021), or danazol (baseline vs. 12 months, p = 0.039).ConclusionAdult, severity of bleeding at presentation, and rapid platelet increases within 1 week were related to excellent corticosteroid responses in ITP patients. These patients may not need combination regimens.

Plasma long noncoding RNAs lncDC and THRIL as potential diagnostic markers of adult primary immune thrombocytopenia.

Immune thrombocytopenia (ITP) is a common acquired hemorrhagic disease without "gold standard" for the diagnosis, long non-coding RNA (lncRNAs) can participate in regulating gene expression through various mechanisms and may play a role in immune intolerance in ITP. Several previous studies have confirmed that lncRNA lncDC and THRIL are involved in the development of autoimmune diseases. This study investigates the relationship between expression levels of two plasma lncRNAs (lncDC and THRIL) and clinical characteristics of adult primary ITP patients, ascertain their potential applications as diagnostic markers of ITP. We recruited 102 subjects, including 41 ITP patients, 41 healthy controls (HCs) and 20 patients under myelosuppression phase after chemotherapy (MS). qRT-PCR was used to detect the expression of two lncRNAs in the peripheral blood plasma of the three groups. Receiver operating characteristic (ROC) curves were used to test the diagnostic efficacy of lncDC and THRIL in ITP. The expression level of lncDC was downregulated in ITP patients compared with HCs (p=. 012) and MS (p=.035), whereas THRIL was significantly upregulated (p=.0005, p < . 0001). We further revealed that lncDC has a high sensitivity (78. 05%), while THRIL has a high specificity (97. 56%). The area under the curve (AUC) (0.869, 95% CI: 0.795-0.943, p < .0001) of the ROC curve for this combination increased significantly. THRIL and lncDC expression levels were changed in adult ITP patients. The lncRNAs lncDC and THRIL can serve as potential diagnostic markers for adult primary ITP.

Use of thrombopoietin receptor agonists in adults with immune thrombocytopenia: a systematic review and Central European expert consensus

There are currently three thrombopoietin receptor agonists (TPO-RAs) approved in Europe for treating patients with immune thrombocytopenia (ITP): romiplostim (Nplate®), eltrombopag (Revolade®), and avatrombopag (Doptelet®). However, comparative clinical data between these TPO-RAs are limited. Therefore, the purpose of this study was to perform a literature review and seek expert opinion on the relevance and strength of the evidence concerning the use of TPO-RAs in adults with ITP. A systematic search was conducted in PubMed and Embase within the last 10 years and until June 20, 2022. A total of 478 unique articles were retrieved and reviewed for relevance. The expert consensus panel comprised ITP senior hematologists from eight countries across Central Europe. The modified Delphi method, consisting of two survey rounds, a teleconference and email correspondence, was used to reach consensus. Forty articles met the relevancy criteria and are included as supporting evidence, including five meta-analyses analyzing all three European-licensed TPO-RAs and comprising a total of 31 unique randomized controlled trials (RCTs). Consensus was reached on seven statements for the second-line use of TPO-RAs in the management of adult ITP patients. In addition, the expert panel discussed TPO-RA treatment in chronic ITP patients with mild/moderate COVID-19 and ITP patients in the first-line setting but failed to reach consensus. This work will facilitate informed decision-making for healthcare providers treating adult ITP patients with TPO-RAs. However, further studies are needed on the use of TPO-RAs in the first-line setting and specific patient populations.

Recombinant human thrombopoietin (rhTPO) of different dosing regimens for refractory/relapsed primary immune thrombocytopenia: a multicenter, randomized controlled trial and pharmacokinetics study

Recombinant human TPO (rhTPO) is effective for refractory/relapsed primary immune thrombocytopenia (ITP), but optimal dosing regimen remains elusive. In this multicenter, randomized, controlled trial, a total of 282 adult ITP patients (mean age 47.3 years; 82 men) with a platelet count ≤30 × 109/L or >30 × 109/L with active bleeding randomly received a once daily (QD) subcutaneous injection of 7500 U (n = 64) or 15000 U rhTPO for 14 injections, or 15000 U or 30000 U rhTPO once every other day (QOD) for 7 injections. The primary outcomes included change from baseline in platelet count and total response rate (TRR) on day 14. On day 14, the median increase of platelet count from baseline was the highest in the 15000-U QD group (167.5 × 109/L, interquartile range [IQR] 23.0–295.0 × 109/L), followed by the 30000-U QOD group (57.5 × 109/L, IQR 9.0–190.0 × 109/L) (ANCOVA P < .001; P = .266 with baseline count as a covariate). The TRR on day 14 was also the highest in the 15000-U QD group (63.2%), followed by the 30000-U QOD group (59.7%). The rate of grade 3 and above adverse events did not differ among the four groups. There were no new safety concerns. All 4 regimens are safe and well-tolerated. The 30000-U QOD regimen is practically indistinguishable in efficacy to the 15000-U QD regimen.

Frequency and Clinical Significance of Antinuclear Antibody Positivity in Immune Thrombocytopenia in Adults

Background Immune thrombocytopenia is an immune-mediated disorder with heterogenous presentation. It shows association with other autoimmune disorders with varying frequency. Objective The objective of this study was to establish the frequency of antinuclear antibody (ANA) in our population and to evaluate its association with severity of clinical presentation, disease remission and association with other autoimmune diseases. Design Cross-sectional study. Methods This was a descriptive cross-sectional study that included 160 patients with immune thrombocytopenia purpura (ITP) presented at National Institute of Blood Disease and Bone Marrow Transplantation from February 2021 to July 2022. Patients were screened for ANA and other causes of secondary ITP. ANA-positive patients were compared with ANA-negative patients in terms of bleeding manifestations and platelet counts at initial presentation, association with other autoimmune diseases and response to first-line treatment. Results In our study 43 (26.9%) patients were ANA positive and 117 (73.1%) were negative for ANA. The initial platelet counts, and bleeding symptoms were not found to be significantly different among the 2 groups. And 79.1% of the ANA-positive patients had other autoimmune markers as well compared to 20.9% ANA-negative patients, showing a significant association ( P&lt;.001). Response to treatment with steroid ± azathioprine assessed at 3 and 6 months were similar in both the groups. Conclusion Our results demonstrate that ANA positivity is not associated with severity of presenting symptoms, initial platelet counts, or response to treatment. However, the presence of ANA is associated with increased risk of other autoimmune diseases in patients with ITP.