Immune-checkpoint blockades (ICBs) are now used in early-stage diseases like triple-negative breast cancer (TNBC). While effective, they can cause severe toxicities. We report the first case of life-threatening immune thrombocytopenia (ITP) induced by pembrolizumab during neoadjuvant chemo-immunotherapy for early TNBC. A 42-year-old woman with early-stage TNBC developed grade 4 thrombocytopenia, diagnosed as ITP, after 107 days of pembrolizumab treatment. She required intensive care unit (ICU) admission and high-dose steroids, and intravenous immunoglobulin therapy, leading to a rapid recovery. ITP is a rare but potentially fatal complication of immunotherapy, with an incidence of less than 1% and a mortality rate of up to 20% in affected patients. Immediate recognition and steroid therapy are critical, as platelet transfusion is usually ineffective. Diagnosis is often delayed due to its similarity to chemotherapy-induced marrow toxicity. Immunotherapy-induced ITP generally contraindicates further use of the treatment. ITP, although uncommon, is a serious complication of immunotherapy requiring immediate intervention. The growing use of immunotherapy necessitates increased awareness of its potential toxicities among healthcare providers.

Immune thrombocytopaenia (ITP) is a rare autoimmune disorder characterized by low platelet count and increased risk of bleeding. This study aimed to be the first publication to characterize the economic burden of bleeding events in patients with ITP in the UK.

We performed a microcosting analysis to estimate the costs associated with bleeding events in patients with ITP. Healthcare resources utilized in the management of bleeds of different severity were costed using well-established UK cost sources. The results were validated through semi-structured interviews with clinical experts.

The severity of bleeding events was classified into four categories, ranging from bleeding managed at home, through mild bleeding managed in the outpatient or day case setting, to serious and life-threatening bleeding events requiring inpatient admission. Total medical costs per event ranged from £2,930 for managing a mild bleeding event, through £16,711 for a serious bleeding event to £32,461 for a life-threatening event. The major cost driver for mild and serious events were intravenous immunoglobulin (IVIg) costs, amounting to £1,614 and £8,071 for the two severity categories, respectively. For life-threatening events, the costs of intensive care unit stay (£9,089) exceeded those of IVIg (£8,071).

Real-world costs of managing bleeding in patients with ITP in the UK are substantial and greater than costs set only based on the UK NHS Tariff. Mitigating the risk of bleeding in patients with ITP is likely to yield not only clinical advantages for patients but also offer substantial cost savings to the health system.

Immune thrombocytopenia (ITP) is an autoimmune disease with isolated platelet count decrease. A subset of patients responds inferiorly to the first-line therapies including glucocorticoid and intravenous immunoglobulins (IVIG), of which the underlying mechanisms have not been fully elucidated. We first found that expression of miR-28-5p was obviously increased in complete responders, and decreased to substantially low levels in partial or non-responders. In the passive ITP model, upregulation of miR-28-5p by injecting agomir slightly improved thrombocytopenia, and obviously inhibited the Rap1b gene expression. Luciferase reporter assay demonstrated there was significant decrease of luciferase activity in 293T cells co-transfected with miR-28-5p mimics and plasmids with Rap1b wide-type sequence. Upregulation of miR-28-5p, and downregulation of Rap1b played a favorable role in reducing B cell infiltration in the marginal zone of spleen in mice. However, miR-28-5p exhibited no significant influence on megakaryocyte maturation in ITP both in vitro and in vivo studies. Finally, we confirmed that miR-28-5p upregulation was associated with superior early treatment response in ITP, and possibly functioned by targeting Rap1b gene to inhibit humoral immunity.

Pediatric immune thrombocytopenia (ITP) is associated with a multifaceted burden on children and their parents/caregivers due to bleeding, fatigue, activity restrictions, and psychological distress. Most children recover within 12 months, but up to 30% develop chronic ITP. While emergent therapies, such as steroids and intravenous immunoglobulin, are effective in many children and transiently raise platelet counts, 38-47% of children require subsequent therapies. The choice of subsequent therapy for individual children with ITP is often complex and the absence of head-to-head comparisons of available therapies and the use of nonstandardized outcomes in randomized clinical trials complicates treatment decisions. Furthermore, medication access varies globally and by age. Additional unmet needs in pediatric ITP include a lack of support and educational resources allowing children and parents/caregivers to effectively participate in treatment decisions, inadequate prediction of treatment response and disease chronicity, heterogeneous approaches to diagnostic evaluation of ITP, scarcity of novel treatments for children unresponsive to current therapies, and the need for a multispecialty approach to support the mental health of children and their families. This review summarizes the known impact of ITP on children and their families, current treatment strategies, and unmet needs in pediatric ITP.

This study aimed to identify novel biomarkers associated with Eltrombopag response in patients with immune thrombocytopenia (ITP) and to investigate the role of macrophage and transitional B cells in ITP pathogenesis. Differentially expressed genes were identified using the GSE112278 dataset, followed by weighted gene co-expression network analysis (WGCNA) to screen hub genes. Single-cell RNA-seq data from GSE196676 were analyzed using the Seurat package to assess immune cell composition, gene expression, and cell-cell communication. CDKN1A expression was experimentally modulated in RAW264.7 macrophages via siRNA knockdown or plasmid overexpression. Phagocytic function was assessed using CFDA-labeled mouse platelets and F4/80 immunofluorescence staining. Molecular docking was conducted to evaluate the interaction between Eltrombopag and CDKN1A. Through intersection analysis, we identified CDKN1A as a key gene influencing the response of ITP patients to Eltrombopag treatment. Single-cell data analysis revealed a significant increase in the proportion of macrophages in ITP patients, accompanied by downregulation of CDKN1A expression in these macrophages, which was closely associated with macrophage activation and enhanced phagocytic capacity. Functional experiments confirmed that CDKN1A knockdown promoted, while overexpression inhibited, macrophage phagocytosis of platelets. Additionally, cell communication analysis demonstrated that macrophages in ITP patients interact with transitional B cells via the TGFβ signaling pathway. Further analysis revealed that a subset of macrophages performs effector functions by differentiating into specialized subtypes that function independently, without direct interaction with other immune cells. Our study identified CDKN1A as a key regulator of Eltrombopag's effectiveness in treating ITP. CDKN1A expression was reduced in macrophages of ITP patients and that it interacted with transitional B cells through the TGFβ signaling pathway to promote disease progression. These findings offer new insights into the pathogenic mechanisms of ITP and suggest CDKN1A as a potential therapeutic target for future interventions.

This phase 4, multicenter, open-label study was conducted to evaluate the safety, efficacy, and treatment satisfaction of switching to avatrombopag from another thrombopoietin receptor agonist (TPO-RA) in patients with immune thrombocytopenia (ITP). Adults who had received ≥90 days of treatment with eltrombopag or romiplostim and had a response (2 platelet counts [PCs] ≥50 × 109/L) switched to avatrombopag with no protocol-defined washout period. The primary end point was the incidence of treatment-emergent adverse events (TEAEs) and serious TEAEs. Secondary end points were the proportion of patients who had a PC between ≥50 × 109/L and ≤200 × 109/L (days 15, 30, 60, and 90) and change from baseline in each domain of the self-administered Treatment Satisfaction Questionnaire for Medication (TSQM) to day 90. Among 60 enrolled patients, 58.3% experienced TEAEs and 10.0% experienced serious TEAEs (1 related to avatrombopag [thrombocytopenia that resolved]; 5 unrelated [1 unrelated death]). A PC ≥50 × 109/L to ≤200 × 109/L was reported for 51.7%, 31.7% (mean PC, 256.2 × 109/L [standard deviation, 176.7 × 109/L]), 55.0%, 60.0%, and 55.0% at baseline and on days 15, 30, 60, and 90, respectively. TSQM scores increased from baseline to day 90 across all domains (mean change: convenience, +13.5; effectiveness, +14.4; global satisfaction, +14.2; side effects, +8.3). There was no correlation between stable avatrombopag dose (day 90) and previous TPO-RA dose (high or low). Patients with ITP may safely switch from another TPO-RA to avatrombopag and maintain adequate PCs while experiencing improved treatment satisfaction. This trial was registered at www.ClinicalTrials.gov as #NCT04638829.

Sustained remissions off-treatment (SROTs) after tapering of thrombopoietin receptor agonists (TPO-RAs) have been reported in 15%-50% of patients with immune thrombocytopenia (ITP). The STIP (Stop TPO-Receptor Agonist in ITP Patients) study is a prospective trial aimed to investigate the clinical effects of romiplostim tapering. Adult patients (22/40) with ITP ≥3 months received romiplostim for 1 year, were tapered and followed for 1 year. Anti-platelet antibodies (APAs), TPO levels and indium-111 platelet scintigraphy were assessed before, during and after romiplostim. Censored survival analysis showed that the probability of SROT at 1 year after tapering was 23.6% (95% confidence interval: 11.0%-50.5%). Patients with SROT had higher platelet levels on romiplostim (median: 332.5 vs. 84.5 × 109/L) and lower romiplostim doses at the start of tapering (median: 1.0 vs. 4.5 μg/kg) compared to those with a non-sustained response (NSR). APAs were detected in 8/25 patients at baseline, of which 5 showed a substantial decrease during romiplostim. The indium-111 scan revealed an improved platelet survival at the start of tapering for 50% of patients with SROT (2/4, missing n = 1) versus none with an NSR (0/14, missing n = 3). Overall, the STIP study demonstrated a probability of SROT of 23.6% in a diverse and largely chronic group of adult patients with ITP.

Thrombopoietin receptor agonists-romiplostim, eltrombopag and avatrombopag-are commonly used as second-line treatments for immune thrombocytopenia (ITP).

A Markov model was developed to estimate the cost effectiveness of the three TPO-RAs in adults with insufficient response to previous treatment from the perspective of the UK National Health Service (NHS). The model considered the effects of bleeding events, concomitant ITP medications, rescue therapies and treatment related adverse events over a lifetime horizon. Model inputs for effectiveness were based on a network meta-analysis and other published literature on ITP management. Other model inputs included costs (e.g., drug acquisition and administration) and healthcare resource utilisation.

Avatrombopag was associated with higher quality-adjusted life-years (QALYs) (10.979) than romiplostim (10.628) and eltrombopag (10.085), producing incremental QALYs of -0.351 and -0.894, respectively. Avatrombopag was associated with lower total costs (GBP £319,334) compared with romiplostim (GBP 406,361 [cost saving of GBP 87,027]) and higher total costs compared with eltrombopag (GBP 313,987 [incremental cost of GBP 5347]). Avatrombopag therefore dominated romiplostim (more effective and less expensive) and was cost-effective versus eltrombopag (incremental cost-effectiveness ratio of GBP 5982 per QALY).

Avatrombopag is a cost-effective treatment compared with romiplostim and eltrombopag for the second-line treatment of adults with ITP from the perspective of the UK NHS.

Avatrombopag is an oral thrombopoietin receptor agonist approved widely for the treatment of adults with chronic immune thrombocytopenia (ITP). However, data in Japanese patients are limited. This confirmatory phase 3, open-label study investigated avatrombopag (initial dose 20 mg/day) in Japanese adults (aged ≥ 18 years) with chronic ITP (≥ 12 months), insufficient response to prior treatment and an average of 2 platelet counts (PCs) < 30 × 109/L. The primary endpoint was the cumulative number of weeks of platelet response (PC ≥ 50 × 109/L) without rescue therapy for bleeding. Secondary endpoints included platelet response rate at Day 8 and safety. In total, 19 patients were enrolled into the 26-week core phase. The mean age was 56.0 years; 78.9% of patients were female. Mean cumulative number of weeks of platelet response was 13.5 (95% CI 9.1-17.8). Platelet response at Day 8 was achieved by 63.2% of patients. In the core phase, adverse events (AEs) occurred in 94.7% of patients and serious AEs in 15.8%. No thromboembolic events or deaths occurred in the core phase. Avatrombopag demonstrated a rapid and durable platelet response and was well tolerated in Japanese patients with chronic ITP. Long-term safety and efficacy are being assessed in the ongoing extension phase.

Immune thrombocytopenia (ITP) is characterized by impaired platelet production and increased platelet destruction. Zanubrutinib is a highly selective next-generation Bruton tyrosine kinase (BTK) inhibitor that may reduce autoantibody production and reduce macrophage Fcγ receptor-mediated platelet destruction. In this single-arm, phase II study, we aimed to assess the efficacy and safety of zanubrutinib in corticosteroid-resistant or relapsed ITP. All patients received 80 mg zanubrutinib once daily for 6 weeks followed by a 20-week safety follow-up period. The primary endpoint was overall response (OR), defined as at least two consecutive platelet counts of at least 30 × 109/L, at least a 2-fold increase in the baseline count, the absence of bleeding, and no need for rescue therapy at 4 weeks. The trial was registered with ClinicalTrials.gov, number NCT05279872. Between January 1, 2022 and October 30, 2022, 20 patients were enrolled. The median platelet count was 19 (10-25) × 109/L at the time of enrollment. Participants had received a median of 4 (3-6) different therapies for ITP. Eleven (55%, 95% CI: 31.5%-76.9%) patients achieved an OR to the intervention. Two (10%) patients achieved a complete response. At the 6-month follow-up, a sustained response was achieved in seven (35.0%, 95% CI: 15.4%-59.2%) patients. There were no grade 4 or worse adverse events or treatment-related deaths. The most common adverse events were upper respiratory tract infection (in 25% of the patients). Zanubrutinib showed an encouraging response rate and tolerability, supporting its therapeutic potential for the treatment of ITP. Trial Registration: ClinicalTrials.gov identifier: NCT05279872.

Treating children with chronic, refractory immune thrombocytopenia (ITP) remains a challenging issue. Conventional treatments, such as glucocorticoids and intravenous immunoglobulin (IVIG), are commonly used; however, some patients exhibit a poor response to these interventions. Throughout the history of traditional Chinese medicine (TCM), numerous texts have documented the use of herbal decoctions to treat hematologic diseases; thereby offering an alternative management strategy for children with chronic ITP.

This report describes a 6-year-and-1-month-old girl with chronic ITP who showed limited response to glucocorticoids and IVIG. Following complementary therapy with a traditional Chinese medicine formula, she achieved a sustained platelet response that was maintained within a safe range, averaging 50,000/μL, over the subsequent three years, with no signs of bleeding.

The pathophysiology of ITP is linked to antiplatelet antibodies and a lack of immune suppression. Scientific studies have shown that TCM formulations, such as Guipi Decoction, Ziyin Jianghou Decoction, and Shengxuexiaoban Capsules, possess immunoregulatory effects that help restore platelet production while exerting anti-inflammatory and hematopoietic properties. For pediatric patients with chronic or refractory ITP, integrative approaches, including TCM, may offer additional therapeutic benefits by enhancing platelet counts.

We herein report a case of concurrent immune thrombocytopenia (ITP) and ulcerative colitis (UC) that achieved remission following mesalazine treatment. A 16-year-old girl presented with severe thrombocytopenia, abdominal pain, and bloody stool. She was initially diagnosed with ITP and then was treated with prednisolone, resulting in an immediate improvement of symptoms. Upon tapering the steroids, the symptoms recurred, thus leading to a subsequent diagnosis of UC via colonoscopy. Treatment with mesalazine promptly induced the remission of both ITP and UC, which was sustained. We reviewed 24 previously documented cases in which the simultaneous flares of UC and ITP were successfully managed.

Background/Objectives: Chronic idiopathic thrombocytopenic purpura (chITP) is an autoimmune disease which develops in 10-30% of patients with newly diagnosed idiopathic thrombocytopenic purpura (ndITP). It is defined as thrombocytopenia which lasts longer than 12 months, with extremely diverse clinical expressions. The aim is to present the most significant clinical and laboratory characteristics of children with chITP. Methods: This is retrospective, observational research, which included children between 2-18 years with chITP who were treated in the Republic of Serbia for 25 years. We analyzed clinical data from personal and family medical histories and different laboratory analyses. Results: The total number of respondents was 152, with female predominance (F:M = 1.27:1) and mild predominance of adolescents. Of the patients, 15% were asymptomatic, but 15% had periodically life-threatening bleeding. Transfusion was not required for 70% of patients. Thirty-five percent of patients had chITP alone, and 45% had high titer levels of autoantibodies. The most frequent comorbidity was Hashimoto thyroiditis (15%). The same percentage (45%) of family members were reported with and without autoimmune diseases. Twenty-five percent of patients were resistant to initial therapy. Helicobacter pylori was detected in 20%, 70% had higher levels of lactate dehydrogenase (LDH), three patients had sufficient serum vitamin D levels, splenomegaly was found in 25%, and accessory spleen in 14% of patients. Around 50% of patients had a platelet count between 20-50 × 10⁹/L, and 40% below 20 × 10⁹/L. Mean platelet volume (MPV) was 10.6 ± 1.4 fL. No dysplastic changes were noted in bone marrow aspirate. Initial first-line therapy was sufficient for 45% of patients, second-line therapy was administered in 25%, splenectomy was performed in 20%, and 10% received all available treatments. Conclusions: The severe clinical form of pediatric chITP is accompanied by a low platelet count, the presence of autoimmune comorbidities, a positive family medical history, resistance to initial therapy, hypovitaminosis D, and rare megakaryocytes in the bone marrow.

A novel, highly purified 10% intravenous immunoglobulin (IVIG) formulation was evaluated for both therapeutic efficacy and safety profile in adult patients diagnosed with persistent or chronic primary immune thrombocytopenia (ITP). This phase III, multicenter, open-label, single-arm clinical trial enrolled Chinese adult patients diagnosed with persistent or chronic ITP presenting with baseline platelet counts below 30 × 109/L. Participants received intravenous administration of 10% IVIG at a standardized dosage of 1 g/kg/day for two consecutive days. The primary efficacy endpoint was defined as the proportion of subjects achieving both a platelet count elevation to ≥ 30 × 109/L and a minimum two-fold increase from baseline values within a 7-day post-treatment observation period following the first dose administration. Seventy-two patients were enrolled and sixty patients completed the study. 52 (72.2%; 95% CI: 60.4, 82.1) patients achieved platelet count ≥ 30 × 109/L and experienced a ≥ twofold increase from baseline within 7 days, and 52 (72.2%; 95% CI: 60.4, 82.1) patients achieved complete response (CR) or response (R) within 7 days. 64 patients (88.9%; 95% CI: 79.3, 95.1) achieved platelet count ≥ 50 × 109/L within 7 days with a median time of 3 days. 71 patients completed the ITP bleeding scale assessment after 7 days, showing a decrease of 0.6 ± 1.07 from baseline. A total of 66 patients (91.7%) reported treatment-emergent adverse events (TEAEs) during the study, and 37 patients (51.4%) reported adverse drug reactions (ADRs). The most prevalent ADRs with an incidence exceeding 5% included headache (n = 12, 16.7%), fever (n = 10, 13.9%), decreased white blood cell count (n = 5, 6.9%), and nausea (n = 5, 6.9%). The therapeutic regimen of 10% IVIG administered at a dosage of 1 g/kg/day for two consecutive days demonstrated both favorable safety profiles and clinical efficacy. These robust findings provide substantial evidence supporting the clinical application of this novel 10% IVIG formulation in the management of adult patients with ITP.

The purpose of this review is to highlight the treatments currently available and those under- going evaluation in clinical trials for the treatment of ITP in order to achieve optimal use of the various existing ITP treatments. Specifically, we point out the indications for use of the various therapies available: corticosteroids, intravenous immunoglobulins (IVIG), thrombo- poietic agents (TPO-RAs), Syk inhibitors: Fostamatinib, antiCD20 monoclonal antibodies i.e. rituximab and the use of splenectomy in ITP. A review of the use of new drugs in ITP is also included in our manuscript: Neonatal Fc receptor (FcRn) antagonists; Bruton tyrosine kinase (BTK) inhibition; B-cell activating factor (BAFF) pathway inhibition; plasma cell depletion (an- tiCD38 monoclonal antibodies); new Syk inhibitors and complement inhibition. We believe that a reader with little knowledge of ITP can gain a clear understanding of the current treatment of ITP and its more or less immediate treatment prospects.

Immune thrombocytopenia (ITP) is an autoimmune condition characterized by low platelet count and increased risk of bleeding. Several pathophysiological processes contribute to the disease, including complement activation by autoantibodies bound to platelet surfaces. This study aimed to assess complement levels in ITP patients and determine their correlation with clinical presentation and disease severity.

This case-control study enrolled 40 patients (both sexes, aged 18-40 years) with primary ITP and 40 healthy controls. All participants underwent a comprehensive health assessment, thorough physical examination, laboratory investigations, and abdominal ultrasound. These included a complete blood count (CBC) with blood film, renal and hepatic function tests, hepatitis B surface antigen (HBsAg), hepatitis C virus antibodies (HCV-Abs), human immunodeficiency virus (HIV) antibodies, hepatitis B core antibody (HBcAb), C-reactive protein (CRP), antinuclear antibody (ANA), thyroid-stimulating hormone (TSH), erythrocyte sedimentation rate (ESR), serum complement levels (C3 and C4), and Helicobacter pylori antigen in stool.

Mean C3 and C4 levels were significantly lower in patients with ITP than in healthy controls. A statistical significant negative correlation was found between CRP and C4 levels in ITP patients. However, no statistically significant relationship was observed between C3 and C4 levels and platelet count in ITP patients, regardless of the presence of bleeding complications.

Complement levels were significantly lower in patients with ITP than in healthy controls. Complement levels were also significantly lower in treatment-naïve patients than in patients who received treatment. Therefore, complement levels could serve as a valuable laboratory test for disease activity.

Background/PurposeAPS ACTION Registry was created to study the natural course of antiphospholipid syndrome (APS) over 10 years in persistently antiphospholipid antibody (aPL) positive patients with or without systemic autoimmune rheumatic diseases (SARDs). Our primary objective was to compare the characteristics of aPL-positive patients with or without thrombocytopenia (TP) and/or autoimmune hemolytic anemia (AIHA).MethodsThe registry inclusion criteria are positive aPL based on the Revised Sapporo APS Classification Criteria, tested at least twice within 1 year prior to enrollment. For the primary comparison of demographic, clinical, and serologic characteristics in this retrospective study, we divided patients into two groups: TP/AIHA ever and never. Thrombocytopenia was defined as a platelet count of <100,000 x 109/L tested twice at least 12 weeks apart, and AIHA was defined as anemia with hemolysis and a positive direct antiglobulin test (DAT). For the secondary analysis, we compared patients with TP versus AIHA, and the immunosuppressive use stratified by systemic lupus erythematosus (SLE) classification.ResultsAs of April 2022, of 1,039 patients (primary aPL/APS: 618 [59%]; SLE classification: 334 [31%]) included in the registry, 228 (22%) had baseline (historical or current) TP and/or AIHA (TP only: 176 [17%]; AIHA only: 35 [3%], and both: 17 [2%]). Thrombocytopenia and/or AIHA was significantly associated with Asian race, SLE classification, cardiac valve disease, catastrophic/microvascular APS, triple aPL (lupus anticoagulant, anticardiolipin antibody, and anti-β2-glycoprotein-I antibody) positivity, and SLE-related serologic and inflammatory markers. When 101/618 (16%) primary aPL/APS patients and 101/334 (34%) SLE patients with TP and/or AIHA were compared, azathioprine and mycophenolate mofetil were more commonly reported in lupus patients, however corticosteroid, intravenous immunoglobulin, and rituximab use were similar between groups.ConclusionIn our large multi-center international cohort of persistently aPL-positive patients, approximately one-fifth had active or historical TP and/or AIHA at registry entry; half of these patients had additional SLE. Cardiac valve disease, catastrophic/microvascular APS, and triple aPL-positivity were aPL-related clinical and laboratory manifestations associated with TP and/or AIHA, suggesting a more severe APS clinical phenotype in aPL-patients with TP and/or AIHA.

This review describes the role of real-world data (RWD) at each step of drug development for rare diseases like immune thrombocytopenia (ITP) and autoimmune hemolytic anemia (AIHA). We also describe the main sources of RWD in rare diseases and how the generation of real-world evidence (RWE) is crucial for decisions of regulatory health agencies regarding drugs for rare disease.

Avatrombopag, a second-generation thrombopoietin receptor agonist (TPO-RA), represents a significant advancement in the treatment of chronic immune thrombocytopenic purpura (cITP) and a potential therapeutic option for other thrombocytopenic disorders. Approved in both the USA and Europe, avatrombopag offers a convenient oral dosing regimen, initiated at 20 mg daily with food, to achieve and maintain platelet counts ≥ 50 × 109/L. Its favorable safety profile, characterized by minimal hepatic toxicity and the absence of dietary restrictions, distinguishes it from older TPO-RAs such as eltrombopag and romiplostim. Clinical trials and real-world data support its efficacy, with over 90% of patients that fail to standard first- and second-line treatments or become unresponsive, achieving target platelet counts, and its hepatotoxicity-free profile makes it particularly advantageous for patients with liver disease or complex comorbidities. Economic evaluations, including a budget impact analysis for the Italian National Health Service, have projected significant healthcare cost savings associated with avatrombopag use, reinforcing its value as a cost-effective therapeutic option. However, challenges remain, including limited data on long-term safety. In this review, we aim to provide a comprehensive synthesis of clinical evidence and real-world data on avatrombopag's efficacy, safety, and pharmacological advantages, while exploring its current and potential therapeutic applications, such as chemotherapy-induced thrombocytopenia and aplastic anemia.

This case report describes the management of 2 pediatric patients with immune thrombocytopenia (ITP) complicated by intracranial hemorrhage. Case 1 involves a 16-year-old who was found to have an acute intracerebral bleed. Partial splenic embolization was performed, which led to improved platelet count and clinical stability. Case 2 details an 8-year-old presenting with a large frontal hematoma with clinical and radiologic signs of herniation. Following complete splenic embolization, his platelet levels rose sufficiently to undergo a successful craniectomy. These cases emphasize the potential role of splenic embolization as an innovative intervention in cases of pediatric ITP with life-threatening bleeding.

Populations with hematologic disorders seeking fertility care often present with a complex clinical picture, including disease-specific sequelae and comorbid conditions. Limited literature exists to help guide fertility clinics on the management of these patients, many of whom require multidisciplinary care coordination centered on patient-specific fertility goals. Thanks to advancements in life-prolonging therapies for hematologic disorders, growing numbers of affected individuals are seeking assisted reproductive technologies for family building. Thus, it is important to be aware of the unique considerations and risks of assisted reproductive technologies for these populations and develop evidence-based care guidelines to optimize outcomes.

Ischemic heart disease is the leading cause of death in the world. Patients who have acute coronary syndrome (ACS) or chronic coronary syndrome (CCS) with significant thrombocytopenia are at high risk for bleeding. In the literature, studies conducted on this patient group are very few. For this reason, although it is difficult for physicians to manage antiplatelet therapy in these patients, the risk of bleeding can be minimized with some current guideline recommendations. This review aims to explore in detail the management of antiplatelet therapy in patients who have moderate and severe thrombocytopenia with coronary artery disease (CAD).

Autoimmune hepatitis (AIH) occasionally complicates immune thrombocytopenic purpura (ITP). The risk of AIH development after prednisolone (PSL) discontinuation and thrombopoietin receptor agonist (TPO-RA) initiation remains underrecognized.

We report two cases of AIH that developed or exacerbated after switching from PSL to TPO-RAs (avatrombopag and eltrombopag) for ITP treatment.

Case 1 developed AIH 8 months after PSL discontinuation and avatrombopag initiation. Case 2 experienced AIH exacerbation with acute decompensation of liver cirrhosis 2 months after PSL discontinuation while on eltrombopag. Both cases showed no improvement after TPO-RA discontinuation but responded well to PSL reintroduction.

PSL discontinuation likely unmasks underlying AIH in ITP patients, with TPO-RAs potentially modulating immune responses. Regular liver function monitoring is essential when transitioning ITP patients from PSL to TPO-RAs.

Immune thrombocytopenia (ITP) is the most common cause of thrombocytopenia in children. This study aimed to describe the diagnostics, patient characteristics, and treatment strategies regarding children with ITP, as well as identify risk factors for chronic disease.

This study included 403 Finnish children aged under 16 years at diagnosis, who were first diagnosed with ITP between 2006 and 2020.

Of the 367/403 patients with complete follow-up data, 242 (65.9%) recovered within three months. Chronic ITP developed in 25.9% of the children. Severe bleeding events occurred in 3.7% of them, with no intracranial bleeding events or deaths reported. Pharmacological treatment was administered to 40.2% of the patients. An elevated risk of chronic ITP was found in the children presenting with an insidious disease onset, female gender, higher age, higher platelet counts, and an absence of recent viral infections. As many as 83.3% of the patients with an insidious disease onset and no recent infections developed chronic ITP.

Most of the children with ITP experienced short and uncomplicated disease courses. Chronic illness was more likely when the disease onset was insidious, the platelet count was not extremely low, and there was no recent history of an infection.

Immune thrombocytopenia (ITP) is a rare hematologic disorder characterized by low platelet counts due to an immune-mediated destruction of platelets. While corticosteroids, intravenous immunoglobulin (IVIG) are the mainstays of treatment, a subset of patients may remain refractory to these therapies. Here, we present a case of a 6-year-old girl diagnosed with refractory ITP, who failed to respond to standard therapies but showed a remarkable clinical improvement with avatrombopag, a thrombopoietin receptor agonist.

This study evaluates the perinatal and neonatal outcomes of pregnant women with severe thrombocytopenia.

A cross-sectional analysis was conducted on pregnant women with platelet counts below 50 × 109/L in a tertiary university hospital between January 2015 and May 2024. Patients were divided into two groups according to their lowest platelet counts. Maternal and neonatal outcomes were systematically recorded and analyzed.

A total of 195 pregnant women were included in the study, 72 of whom were in Group A (0-30 × 109/L) and 123 in Group B (30-50 × 109/L). In our study, immune thrombocytopenic purpura was the most common cause of severe thrombocytopenia, accounting for 56.6 % of cases. Significant differences were observed in the rates of preterm birth (<34 weeks) and neonatal intensive care unit (NICU) admission, with higher rates in Group A (p=0.035 and p=0.05, respectively). No significant differences were found in other maternal and neonatal outcomes, including postpartum hemorrhage rates, between the two groups.

In pregnancies complicated by severe thrombocytopenia with a platelet count <30 × 109/L, there is an increased risk of preterm birth before 34 weeks and NICU admission.

Advancements in the understanding of ITP pathogenesis have led to significant improvements in disease management through the use of both traditional immunosuppressive strategies and novel targeted therapies. However, a subset of patients remains refractory to treatment or achieves only transient benefits, underscoring the need for alternative therapeutic approaches. Bruton's tyrosine kinase (BTK) inhibitors have emerged as a promising strategy for autoimmune cytopenias, including ITP, due to their ability to modulate key immune pathways. Rilzabrutinib, an oral, reversible BTK inhibitor, represents a novel therapeutic approach for ITP. Rilzabrutinib, an oral, reversible BTK inhibitor, offers a novel mechanism of action by preserving platelet aggregation while reducing macrophage-mediated platelet clearance, distinguishing it from irreversible BTK inhibitors. This review provides an updated and comprehensive analysis of the Phase 1/2 LUNA 2 trial and its long-term extension, contextualizing rilzabrutinib within the broader treatment landscape. We also offer a comparative assessment of other BTK inhibitors investigated for ITP and discuss rilzabrutinib's potential positioning relative to existing therapies, including thrombopoietin receptor agonists (TPO-RAs), rituximab, fostamatinib, and immunosuppressants. Results from the phase 1/2 LUNA 2 trial and its long-term extension demonstrated that Rilzabrutinib induced a durable platelet response in 40% of patients, with a median time to response of 11.5 days. The treatment exhibited a favorable safety profile, with predominantly grade 1 or 2 adverse events and no significant safety concerns commonly associated with BTK inhibitors, such as increased bleeding risk, hepatic toxicity, or cardiac arrhythmias. Preliminary data presented at ASH 2024 from the ongoing Phase 3 LUNA 3 trial, a randomized, double-blind study, further support rilzabrutinib's efficacy and long-term safety. If confirmed, these findings suggest that rilzabrutinib could represent a valuable therapeutic option for patients with refractory ITP, addressing a critical unmet need and potentially redefining treatment paradigms.

This study aimed to develop and validate a risk prediction model for moderate to severe bleeding in children with immune thrombocytopenia (ITP). Data from 286 ITP patients were prospectively collected and randomly split into training (80%) and test (20%) sets. Least Absolute Shrinkage and Selection Operator (LASSO) regression was used for feature selection. Among seven machine learning algorithms, the eXtreme Gradient Boosting (XGBoost) model demonstrated the best performance (AUC = 0.886, 95% CI: 0.790-0.982) and was selected as the optimal model. Shapley Additive Explanations (SHAP) were used for model interpretation, identifying child age, age at diagnosis, and initial platelet count as key predictors of moderate to severe bleeding risk.

The XGBoost-based prediction model shows strong predictive performance and could assist healthcare providers in identifying high-risk ITP patients, supporting appropriate clinical decision-making.

ChiCTR2100054216, December 11, 2021 What is Known: • Current clinical practice relies solely on platelet counts to guide hospitalization and treatment in ITP children, often overlooking bleeding manifestations, leading to delayed or inappropriate treatment. Existing severe bleeding risk prediction models are primarily designed for adults and lack applicability to children.

 • This study prospectively collected data, enhancing accuracy. A novel machine learning-based prediction model was developed to assess moderate to severe bleeding risk in pediatric ITP patients.

Despite using state-of-the-art methodologies like Grades of Recommendation, Assessment, Development and Evaluation (GRADE), current guideline development frameworks still rely heavily on panellists' intuitive integration of evidence related to the benefits and harms/burdens of health interventions. This leads to the 'black-box' and 'integration' problems, highlighting the lack of transparency in guideline decision-making. Combined with humans' limited capacity to process the large volumes of information presented in Summary of Findings (SoF) tables-the primary output of systematic reviews that underpin guideline recommendations-this reliance on non-explicit processes raises concerns about the trustworthiness of clinical practice guidelines.

SoF tables provide the best available evidence, derived from frequentist or Bayesian estimation frameworks. Decision analysis, which integrates both types of estimates but considers intervention consequences, is the only analytical approach that combines multiple outcomes (benefits, harms and costs) into a single metric to support decision-making. Such analysis seeks to identify the optimal decision by balancing harms, benefits and uncertainties. This paper leverages the PICO format (Population, Intervention, Comparison(s), Outcome) as a conceptual basis for deriving SoF tables. Subsequently, we propose a solution to GRADE's "black-box" and "integration" problems by matching PICO-based SoF with decision models.

We succeeded in connecting the PICO framework to simple decision-analytical models, restricted to time frames supported by empirically verifiable evidence, to calculate which competing intervention offers the greatest benefit (net differences in expected utility; ΔEU). The single metric [ΔEU] enabled a simple, transparent and easy-to-understand assessment of the superiority of competing management strategies across multiple outcomes (considering both benefits and harms), addressing the 'black-box' and 'integration' problems. Completing a SoF-based decision model takes about 10 min. Not surprisingly, the recommendations based on ΔEU may differ from the intuitive recommendations of panels.

We propose that incorporating the straightforward and transparent modelling into guideline panels' decision-making processes will enhance their intuitive judgements, resulting in more trustworthy recommendations. Given the simplicity of calculating ΔEU, we advocate for its immediate inclusion in systematic reviews and SoF tables.

Patients with immune thrombocytopenia (ITP) suffer from an autoimmune bleeding disorder with an isolated low number of platelets. Platelets and megakaryocytes are targeted by the immune system, due to a loss of immune tolerance, via the action of platelet-autoantibodies and/or cytotoxic T cells. ITP is a highly variable disorder regarding the underlying biological mechanisms, disease trajectories and treatment responses. Predictive indicators are therefore strongly warranted. To analyze the predictive response to the thrombopoietin receptor agonist eltrombopag, in this issue of the British Journal of Haematology, Osuna-Gomez and co-workers research platelet-leukocyte complexes in 38 ITP patients upon treatment with eltrombopag. Elevated platelet counts upon treatment with eltrombopag were associated with increased complexes of platelets bound to leucocytes. A higher percentage of monocytes bound to platelets, with an increased IL-10 production in monocytes, was found to be associated to a favorable clinical response to treatment with eltrombopag. Further validation is required but these findings reveal the potential of analyzing platelet-monocyte complexes as a predictive indicator for the clinical response to eltrombopag in patients with ITP. Commentary on: Osuna-Gómez et al. Interplay of leucocyte-platelet complexes and clinical response to eltrombopag in immune thrombocytopenia patients. Br J Haematol 2025; 206:1200-1212.

Immune thrombocytopenic purpura (ITP) is an acquired autoimmune disease characterized by reduced platelet counts due to immune system dysregulation caused by many factors, including genetics, autoimmune diseases, infections, and inflammations. Therefore, the current study aimed to evaluate immunological markers such as the expression level of lysosomal associated membrane protein 3 (LAMP-3), also known as CD63, and the expression level of Fc-gamma receptor I (FcγRI), also known as CD64 and also investigate the association of Fc-gamma receptor IIIA (FcγRIIIA) 158 V/F polymorphism to the risk of ITP.

A total of 180 subjects; 60 ITP patients, 60 patients with thrombocytopenia of other causes and 60 controls were enrolled into our study. The expression level of CD63 was done using reverse transcription quantitative PCR (RTqPCR), while CD64 expression level was done by flow cytometry. The polymorphism of FcγRIIIA 158 V/F gene was analyzed by polymerase chain reaction followed by restriction fragment length polymorphism (PCR-RFLP) analysis. Finally, CD63 and CD64 protein-protein interactions were done by using the STRING online database.

The expression of CD63 was significantly elevated in ITP patients than thrombocytopenia patients and healthy control. Also there was high expression level of CD64 on granulocytes and monocytes from ITP patients than other groups. Receiver operating characteristic curve (ROC curve) analysis of CD63 showed an area under the curve (AUC) revealed of 1.00, sensitivity of 100% and specificity of 100%; while for CD64 on granulocytes, AUC of 0.998 as well as a sensitivity of 96.66% and specificity of 93.33%. Regarding FcγRIIIa 158 V/F polymorphism, all patients and healthy volunteers included in this study showed the wild FF genotype.

The expression of both CD63 and CD64 were significantly increased in ITP patients and could be good biomarkers to diagnose ITP. Additionally, there is no association between FcγRIIIa 158 V/F polymorphism and the risk of ITP disease.

Immune thrombocytopenic purpura (ITP) is an autoimmune disorder characterized by the production of autoantibodies targeting platelet membrane antigens, leading to platelet destruction by the reticuloendothelial system. This results in a significant drop in platelet count to 100 × 10⁹/L or lower due to the formation of autoantibodies and immune complexes. Some studies suggest a potential link between Helicobacter pylori infection and ITP. This report presents a case of ITP in a patient with an H. pylori infection. To our knowledge, this is one of the unique and interesting reported cases of such a severe platelet deficiency, where the platelet count dropped to 1,000 cells/µL in the presence of an aggressive H. pylori infection. A 46-year-old male was admitted with mild gum bleeding and petechiae on his lower limbs. His medical history included chronic diabetes mellitus, dyslipidemia, and hypertension, though his clinical and vital signs were normal. Laboratory tests revealed a critically low platelet count of 3,000 cells/µL, leading to a provisional diagnosis of ITP. The patient was started on intravenous (IV) methylprednisolone (1 g for three days), IV immunoglobulin (0.4 g/kg for five days), proton pump inhibitors, calcium, and vitamin D supplements. However, there was no significant response to the treatment. Additional immunological and viral tests yielded negative results. Given this, an H. pylori test was conducted, which confirmed an infection. The patient was started on H. pylori eradication therapy. The platelet count improved to 48,000 cells/µL, but it dropped again to 1,000 cells/µL after a few days. Various treatment strategies were implemented to manage both ITP and H. pylori. After two months, the H. pylori urea breath test returned negative, and the patient's platelet count normalized. The patient was maintained on folic acid (5 mg daily) and eltrombopag (50 mg daily), with regular hematology follow-ups ensuring stable platelet levels. This case underscores a rare presentation of ITP associated with severe thrombocytopenia (1,000 cells/µL) and aggressive H. pylori infection. The findings emphasize the importance of considering H. pylori in the differential diagnosis of ITP and highlight the necessity of identifying underlying causes for effective treatment.

Eltrombopag (ELT) is a thrombopoietin-receptor agonist that stimulates platelet (PLT) production in patients with primary immune thrombocytopenia (ITP). One potential mechanism of ELT is modulating the inflammatory response by increasing PLTs binding to leucocytes. This study examined the effect of ELT on leucocyte-PLTs complexes in 38 ITP patients. Patients, predominantly females with a mean age of 59 years, underwent treatments like corticosteroids, intravenous immunoglobulin and splenectomy. Compared to healthy donors, ITP patients exhibited lower percentages of lymphocyte with bound PLTs, but similar monocyte- or neutrophil with bound PLTs. ELT treatment increased PLTs counts and all types of leucocyte with bound PLTs. Network analysis showed dynamic changes in leucocyte with bound PLTs relationships due to ELT. Machine learning indicated that higher percentages of monocytes with bound PLTs were linked to a better clinical response to ELT. A possible mechanism was an increased IL-10 production in monocytes with bound PLTs from responder patients. This study provides insights into the immunological changes in ITP patients undergoing ELT and suggests potential predictive biomarkers for treatment response and disease monitoring.

Immune thrombocytopenia (ITP) is characterized by immune-mediated platelet destruction and impaired megakaryocyte maturation. Hypoxia-inducible factor-1α (HIF-1α), pivotal in the development of megakaryocytes and immune regulation, is downregulated in ITP. Roxadustat, which stabilizes HIF-1α, has emerged as a potential therapeutic drug for ITP that acts by enhancing HIF-1α-mediated megakaryocyte development and modulating immune responses.

This study evaluates the safety profile of roxadustat and its therapeutic efficacy for ITP treatment using Mendelian randomization (MR) analysis.

We used expression quantitative trait loci data for roxadustat's target genes (EGLN1, EGLN2, and EGLN3) and genetic associations with ITP and adverse outcomes from the Open Genome-Wide Association Study project. MR analysis included inverse-variance weighted, MR-Egger regression, weighted median, and MR pleiotropy residual sum and outlier methods to evaluate pleiotropy. Heterogeneity was assessed using Cochran's Q statistic and I2 measure with sensitivity analyses. A meta-analysis was performed to integrate effect sizes from multiple literature sources.

MR analysis revealed a significant association between roxadustat and reduced ITP risk (odds ratio, 0.79; 95% CI, 0.66-0.95; P = .01) with no evidence of horizontal pleiotropy. Meta-analysis confirmed the protective effect of roxadustat on ITP. Utilizing the expression quantitative trait loci of roxadustat's target gene EGLN1 as instrumental variables, an MR analysis of 39 potential adverse reactions revealed no significant increase, suggesting a favorable safety profile for roxadustat.

Roxadustat demonstrates a potential protective effect against ITP without increasing the risk of adverse outcomes, suggesting its promise as a therapeutic option for ITP and warranting further investigation.

Previous guidelines for the treatment of immune thrombocytopenia (ITP) have traditionally focused on a dichotomy between pediatric and adult ITP. Adolescents and young adults (AYAs) do not neatly fit into either the pediatric or adult ITP group. A deeper understanding of ITP's natural history, risk factors for chronicity, and outcomes in AYAs is a crucial first step toward developing tailored treatment algorithms. Such data could form the basis for recommendations targeting this underrepresented yet clinically distinct population. Ultimately, age-adapted trials may improve long-term outcomes, reduce toxicity, and enhance quality of life for AYAs with ITP. The AYAs collaboration-drawing on data from the Pediatric and Adult Registry on Chronic ITP (PARC-ITP), Registre Midi- Pyrénéen-France (CARMEN-France) adult registry in Toulouse, and the National Prospective Cohort for Children with Chronic Autoimmune Cytopenia (OBS'CEREVANCE) in Bordeaux, France-aims to address the information gap in AYAs with ITP. To date, four analyses have been undertaken (using data from 2004 to 2021), each addressing the major clinical aspects of ITP in patients aged 12-25 years: (1) newly diagnosed ITP, (2) chronic disease, (3) refractory courses, and (4) secondary (sITP) forms.

There is an emerging understanding of the increased risk of stroke in patients with immune thrombocytopenic purpura (ITP) and immune thrombotic thrombocytopenic purpura (iTTP). We aimed to determine the prevalence and characteristics of acute ischemic stroke (AIS) and intracranial hemorrhage (ICH) in patients with ITP and iTTP in a systematic review and meta-analysis.

We used PubMed, Embase, Cochrane, Web of Science, and Scopus using text related to ITP, iTTP, stroke, AIS, and ICH from inception to 11/3/2023. Our primary outcome was to determine prevalence of AIS and/or ICH in a cohort of ITP or iTTP patients (age > 18). Our secondary outcomes were to determine stroke type associated with thrombopoietin receptor agonists (TPO-RAs) in ITP patients, as well as risk factors associated with stroke in ITP and iTTP patients.

We included 42 studies with 118,019 patients (mean age = 50 years, 45% female). Of those, 27 studies (n = 116,334) investigated stroke in ITP patients, and 15 studies (n = 1,685) investigated stroke in iTTP patients. In all ITP patients, the prevalence of AIS and ICH was 2.1% [95% Confidence Interval (CI) 0.8-4.0%] and 1.5% (95% CI 0.9%-2.1%), respectively. ITP patients who experienced stroke as an adverse event (AE) from TPO-RAs had an AIS prevalence of 1.8% (95% CI 0.6%-3.4%) and an ICH prevalence of 2.0% (95% CI 0.2%-5.3%). Prevalence of stroke did not significantly differ between all ITP patients and those treated with TPO-RAs. iTTP patients had a prevalence of AIS and ICH of 13.9% (95% CI 10.2%-18.1%) and 3.9% (95% CI 0.2%-10.4%), respectively. Subgroup analysis revealed the prevalence of AIS and ICH was greater in iTTP patients vs. all ITP patients (p < 0.01 and p = 0.02, respectively). Meta-regression analysis revealed none of the collected variables (age, sex, history of diabetes or hypertension) were risk factors for stroke in all ITP patients, although there were high levels of data missingness.

Prevalence of different stroke types was lower in all ITP patients vs. iTTP patients. Additionally, ITP patients experienced a similar prevalence of stroke regardless of if they were specifically denoted to have been treated with TPO-RAs or not, supporting the continued use of TPO-RAs in management. Risk factors for stroke remain unclear, and future studies should continue to investigate this relationship.

Autoimmune liver diseases (AiLDs), including autoimmune hepatitis (AIH), primary biliary cholangitis (PBC), and primary sclerosing cholangitis (PSC), are immune-mediated conditions associated with significant hepatic and systemic manifestations. Among these, cytopenias-defined as reductions in blood cell counts affecting single or multiple lineages-represent a clinically important, though often under-recognized, complication. Cytopenias in AiLDs arise from diverse mechanisms, including immune-mediated destruction, hypersplenism due to portal hypertension, bone marrow suppression, and nutritional deficiencies. These abnormalities can exacerbate bleeding, infections, or fatigue, complicating the disease course and impacting therapeutic strategies. Immune-mediated cytopenias, such as autoimmune hemolytic anemia (AIHA), immune thrombocytopenic purpura (ITP), and autoimmune neutropenia (AIN), are more frequently associated with AIH, whereas cytopenias in PBC and PSC are largely attributed to hypersplenism. Diagnostic evaluation involves a systematic approach combining clinical history, laboratory testing (e.g., complete blood counts, Coombs tests, and nutritional assessments), imaging studies, and bone marrow evaluation in complex cases. Treatment strategies aim to address the underlying cause of cytopenias, including immunosuppressive therapy for autoimmune mechanisms, beta-blockers or splenectomy for hypersplenism, and supplementation for nutritional deficiencies. Challenges include distinguishing between immune- and hypersplenism-related cytopenias, managing drug-induced cytopenias, and optimizing care in transplant candidates. The recently recognized IgG4-related disease, often mimicking cholestatic AiLDs, adds another layer of complexity, given its association with autoimmune cytopenias and hypersplenism. This review aims to act as a guide for the clinician dealing with patients with AiLDs with respect to the occurrence of cytopenias, with a specific focus on pathophysiology and management of these cytopenias. Furthermore, there need to be enhanced multidisciplinary discussions about those patients between the hematologists and hepatologists, with a maintenance of a high index of suspicion for the rarer causes of cytopenias in AiLDs on the part of the treating physician, and there is a need for further studies to elucidate the mechanisms behind the occurrence of cytopenias in AiLDs.