Limited data exist on how patients and physicians perceive immune thrombocytopenia (ITP) symptoms and treatment-related burden. I-WISh (ITP World Impact Survey) 2.0 surveyed 1018 patients and 431 physicians in 15 countries to characterize the impact of ITP and its treatments on patients. Approximately one-third of patients reported that ITP had a high impact on daily activities and family/social life, and 54% reported that it had a high impact on emotional wellbeing. Patients and physicians generally aligned on symptoms and treatment goals, but more patients (48%) than physicians (29%) reported fatigue as common and problematic. Ninety-seven percent of patients reported that they had received treatment for ITP, most commonly corticosteroids. Most patients and 54% of physicians were satisfied with available treatments, although patients reported treatment-related burdens. Twenty-eight percent confirmed they would have chosen a different treatment. Two-thirds of patients were in a stable, sustained remission, and most had never paused treatment (67%). Nevertheless, two-thirds of patients preferred limiting time on treatment and/or not being on lifelong treatment. I-WISh 2.0 emphasizes the extensive disease and treatment burden faced by patients living with ITP, especially the impact of fatigue. It also reminds us that shared decision-making is needed to ensure treatment goals are aligned with patient expectations, including health-related quality of life.

Immune thrombocytopenia (ITP) is a complex autoimmune disorder characterized by accelerated destruction of peripheral platelets and impaired megakaryopoiesis. While the cellular effectors, dysregulated T cells, hyperactive B cells and phagocytic macrophages are well characterized, the upstream epigenetic mechanisms orchestrating this multicellular immune network remain largely elusive. This review explores the hypothesis that microRNAs (miRNAs) may serve as critical architects of immune dysregulation and bone marrow failure in ITP. We evaluate the clinical utility of circulating miRNAs as non-invasive biomarkers for diagnosis, risk stratification and predicting response to steroid and thrombopoietin receptor agonists therapies. Finally, we address current translational difficulties, such as data fragmentation and pre-analytical variables. We propose a roadmap for integrating functional validation with multi-omics, utilizing miRNA-based approaches to facilitate and advance precision medicine in ITP.

Thrombocytopenia is a frequent hematological disorder associated with an increased risk of bleeding across diverse clinical settings. Supportive management aims to prevent hemorrhagic complications, relieve symptoms, and address underlying causes. This narrative review summarizes evidence from randomized trials, systematic reviews, and international guidelines on the supportive management of thrombocytopenia in hematological, oncological, surgical, and critical care settings. Platelet transfusion remains the cornerstone of supportive treatment in patients with severe thrombocytopenia or active bleeding. Prophylactic transfusion is generally recommended in high-risk patients with bone marrow suppression, although thresholds vary according to clinical context and bleeding risk. Therapeutic transfusion is indicated in the presence of active bleeding or prior to urgent procedures. Adjunctive hemostatic therapies may provide additional benefit in selected scenarios. In many clinical situations, recommendations are based on limited evidence, supporting an individualized and restrictive transfusion approach.

Neuraxial anesthesia is used for pain management in surgical and nonsurgical settings. Spinal/epidural hematomas likely occur in between 1:10 000 and 1:200 000 procedures. Risk is believed to be greater in patients with bleeding disorders/thrombocytopenia, and there are no existing comprehensive recommendations to guide neuraxial anesthesia in these patients. The study’s objective was to develop recommendations to advise clinicians on treatment thresholds for neuraxial anesthesia in patients with platelet disorders/coagulation defects. A 4-round electronic modified Delphi consensus study was conducted. A steering committee generated the original Delphi statements and refined them based on panelist feedback. Consensus was achieved if ≥70% of participants agreed/strongly agreed or disagreed/strongly disagreed with a statement. This project was endorsed by the International Society on Thrombosis and Haemostasis Scientific and Standardization Committee Subcommittee on von Willebrand Factor. Forty-five experts participated (42% response rate) with an essentially equal number of hematologists and anesthesiologists. Thirty consensus statements were developed for 11 disorders ranging from various causes of thrombocytopenia, inherited platelet function disorders, and single or multiple coagulation defects in obstetrical and nonobstetrical patients. Risk of sampling bias is present due to a predominantly North American sample, attrition (common in Delphi studies), and steering committee participation in the Delphi rounds. This is the first set of consensus recommendations for neuraxial anesthesia in adult patients with an array of platelet disorders/coagulation defects. These recommendations, based on the best available evidence and expert opinion, provide a decision framework for clinicians when faced with this challenging scenario.

Thrombocytopenia (TCP) commonly complicates chronic liver disease (CLD), with platelet transfusion traditionally serving as the standard therapeutic approach, despite associated risks such as infection, alloimmunization, and transfusion reactions. Recent advancements have introduced thrombopoietin receptor agonists (TPO-RAs), including avatrombopag and lusutrombopag, as safe and effective alternatives for managing TCP in CLD patients who are scheduled for invasive procedures. This review discusses the pathogenesis underlying TCP in CLD, current therapeutic approaches, and evaluates the efficacy and safety profiles of avatrombopag and lusutrombopag. Furthermore, based on clinical expertise and a thorough assessment of the available evidence, the review provides practical recommendations to assist healthcare professionals in managing TCP in CLD patients, especially those undergoing invasive medical procedures or surgeries. These recommendations emphasize individualized treatment decisions guided by the severity of TCP and procedure-related bleeding risks, highlighting the role of TPO-RAs as optimal and beneficial therapeutic alternatives to platelet transfusions.

Primary immune thrombocytopenia (ITP) is a disorder characterized by enhanced platelet clearance and impaired production due to immune dysregulation. Central to its pathogenesis are platelet autoantibodies, T-cell-mediated processes, and altered cytokine profiles, which exacerbate clearance and hinder production. These mechanisms mirror other immune-mediated diseases and contribute to symptoms such as fatigue and thromboembolism. Despite extensive research, the inflammatory role in ITP remains unclear, with variability across studies underscoring the need for further investigation to optimize therapies. This study aims to summarize the evidence on inflammatory cytokines, inflammasomes, and neutrophil extracellular traps (NET) in adult primary ITP. A systematic literature review was conducted using Embase and MEDLINE (search date 9 January 2024), covering publications from the past decade. Observational studies and clinical trials reporting inflammatory markers were included (79 studies). Most studies were case-control (69.7%) and conducted in China (77.2%). Activation of multiple immune and inflammatory pathways was observed. T helper 17 (Th17; n = 21) and T follicular helper cells (n = 4) demonstrated involvement, with Th17-derived interleukin-17 (IL-17) contributing prominently to the inflammatory milieu. NLRP3 inflammasome hyperactivity/increased expression (n = 6 studies) emerged as a significant pathway, and strongly associated markers (IL-18 [n = 4]) were elevated. Additionally, NET and neutrophil activation promoted inflammation and thrombosis (n = 2). In conclusion, immune dysregulation from Th17 cell pathways and NLRP3 inflammasome strongly contribute to inflammation in adults with primary ITP, with IL-18 and IL-17 linked to disease activity/progression. The findings suggest a need for novel therapies to target immune dysregulation and clarify their roles in ITP.

Immune thrombocytopenia (ITP) is an autoimmune disorder with increased risk of bleeding due to a low number of platelets. The pathophysiology is complex and not fully understood, but platelet autoantibodies and/or CD8+ T-cells are responsible, via diverse mechanisms, for disrupting platelet production and enhancing platelet destruction. The symptomatology of ITP seems to be more complex than has traditionally been perceived as thrombocytopenia and bleeding as the disease often has impact on the health-related quality of life and daily functions. The management thus requires a holistic approach and patient involvement at every stage. Corticosteroids still represent the cornerstone of the first-line treatment. Treatment with corticosteroid should not exceed 6–8 weeks. Patients who fail to achieve remission with a short course of corticosteroids may require a second-line therapy. Most guidelines recommend starting with a thrombopoietin receptor agonist (TPO-RA), rituximab, or fostamatinib since these agents have been investigated in randomized trials and have well-characterized efficacy and safety profiles. Patient involvement to reach a shared decision regarding choice of therapy is essential as these treatments have different modes of administration and mechanisms of action. Less than 10% of adults ITP patients will fail to respond to and/or be intolerant of multiple second-line therapies and would thus require a third-line therapeutic option. Such patients may respond well to a combination of TPO-RA and an immunomodulatory agent. Splenectomy or a continuation with nontherapeutic agents that has different mechanism of action may be an alternative approach.

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.

Abstract Thrombopoietin receptor agonists, for example eltrombopag, are standard second-line treatment for immune thrombocytopenia (ITP). Eltrombopag has demonstrated high response rates, both in clinical trials and in routine practice studies. However, some patients with ITP are refractory to this drug. Next-generation sequencing (NGS) may help us identify underlying molecular biology variants that may be involved in eltrombopag refractoriness. Our multicenter national NGS study investigated 110 genes of the most important cell-signaling pathways involved in the mechanism of action of eltrombopag in 35 refractory cases and 35 eltrombopag-responsive controls. Our refractory population comprised 51.4% men with a median age at diagnosis of 48 (range, 38-69) years and a median platelet count of 7 × 109/μL (range, 4 × 109/μL to 16 × 109/μL). At eltrombopag initiation, 78.3% had chronic ITP with a median platelet count of 8 × 109/μL (range, 5× 109/μL to 30 × 109/μL). Treatment with eltrombopag was maintained for a median of 3 (range, 1-9) months before discontinuation. No major grade 3-4 side effects were observed. Several statistical differences were observed in relation to the control responders. Of the total sum of the NGS variants found, 13 variants with statistical significance (P ≤ .05) between case and controls were observed. Two of these have been shown to be associated with cancer. Seven variants are considered benign. Four variants are not previously described, and their significance is unknown. To our knowledge, none of the 13 variants described here has ever been correlated with ITP or eltrombopag refractoriness. Further studies are required to establish their role in this setting.

BACKGROUND AND OBJECTIVES:The management of ITP has evolved with evidence-based international guidelines. However, Iraq's unique challenges, including variations in clinical practice and treatment disparities, necessitate localized guidance to bridge global recommendations and real-world practice. This expert consensus aims to provide a comprehensive and practical framework for diagnosing and managing ITP within the Iraqi healthcare setting. METHODS:A 16-member multidisciplinary ITP specialist panel (Iraq, Norway, UK), including hematologists, laboratory experts, and related specialists, conducted a systematic PubMed / PubMed Central / Embase review (January 2003-December 2024) using key terms 'primary immune thrombocytopenia' and 'idiopathic thrombocytopenic purpura' (English human studies, excluding conference abstracts). Using a modified Delphi method, consensus was reached on 43 ITP diagnosis/treatment/management statements. After a single voting round, the panel refined the recommendations to ensure their applicability to Iraq's healthcare system. Final recommendations were categorized using evidence grading system. RESULTS:Corticosteroids were the preferred first-line therapy, with intravenous immunoglobulin (IVIG) reserved for urgent platelet elevation. The panel discouraged prolonged corticosteroid use due to adverse effects and defined clear criteria for second-line therapies. Thrombopoietin receptor agonists (TPO-RAs) and rituximab were recommended second-line, while splenectomy was considered a last resort, only after the failure of multiple medical therapies. Special populations received tailored recommendations, including pregnant patients, pediatric cases, and high-thrombosis-risk individuals. Recommendations incorporated quality of life, emphasizing patient-centered care and minimizing unnecessary medication exposure. CONCLUSION:This expert consensus provides a structured, evidence-informed approach to ITP diagnosis and management in Iraq, balancing best practices with local healthcare realities.

Immune thrombocytopenia (ITP) is an autoimmune disease characterized by an isolated thrombocytopenia and variable phenotype as some patients suffer no bleeding whilst others have bleeding from mild to severe, which may be fatal. This variability probably reflects the disease's complex pathophysiology; a dysregulated hyperreactive immune effector cell response involving the entire adaptive immune system (e.g. B and T cell subsets) that leads to platelet and megakaryocyte (MK) destruction. It appears that these effector responses are due to a breakdown in immune tolerance, and this is characterized by defects in several immunosuppressive cell types. These include defective T regulatory cells (Tregs), B regulatory cells (Bregs) and Myeloid-derived suppressor cells (MDSC), all of which are all intimately associated with antigen presenting cells (APC) such as dendritic cells (DC). The loss of this immunosuppressive axis allows for the activation of unchecked autoreactive T cells and B cells, leading to the development of autoantibodies and cytotoxic T cells (CTL), which can directly destroy platelets in the periphery and inhibit MK platelet production in the bone marrow (BM). This review will focus on the effector cell mechanisms in ITP and highlight the defective immunosuppressive axis that appears responsible for this platelet-specific immune hyperreactivity.