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Immune thrombocytopenic purpura (ITP) is an uncommon condition resulting from the autoimmune destruction of platelets. A man in his mid-30s, who had received three doses of the SARS-CoV-2 vaccine a year prior, was diagnosed with ITP 3 weeks after contracting COVID-19. Mechanisms of SARS-CoV-2 induced thrombocytopenia may include bone marrow depletion, coagulation consumption, mutations resulting in cytokine release or molecular mimicry leading to autoimmunity. Initial treatment involved glucocorticoids, but the disease course progressed into glucocorticoid-resistant ITP. Subsequently, the patient was diagnosed with ITP refractory to intravenous immunoglobulin, thrombopoietin receptor agonist, rituximab, cyclophosphamide, inhibitors of BTK and SYK, and other pharmacological agents. Despite exhaustive medical interventions, bleeding diathesis and platelet counts worsened, so the patient underwent a splenectomy resulting in the resolution of the thrombocytopenia., Competing Interests: Competing interests: None declared., (© BMJ Publishing Group Limited 2024. No commercial re-use. See rights and permissions. Published by BMJ.)

Vaccine-induced immune thrombocytopenia and thrombosis (VITT) is a newly recognized syndrome mediated by anti-platelet factor 4 antibodies induced by Covid-19 adenovirus-vectored vaccines including ChAdOx1 nCoV-19 and Ad26.COV2.S. This study validated a proposed Brighton Collaboration case definition for VITT. A data collection form was developed and used to capture the variations in VITT criteria and assess their level of diagnostic certainty from adjudicated positive VITT case datasheets in Germany (n = 71), UK (n = 220), Australia (n = 203), and Taiwan (n = 56). We observed high prevalence of each component of the proposed VITT definition in positive cases (84%-100%), except for the occurrence of thrombosis or thromboembolism criterion in only 34% of VITT cases in Taiwan. The sensitivity of this proposed definition was 100% for Germany and UK, 92% for Australia, and 89% for Taiwan cases. These findings support the validity of this case definition for VITT., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: H. Tran reports project grant funding support outside of the submitted work from AstraZeneca and Sanofi. W.-I. Huang is a member of the national enhanced passive Covid-19 vaccine safety surveillance team in Taiwan. J. Buttery has served as an independent data monitoring committee member for CEPI SPEAC, GSK, Serum Institute of India, SK Biosciences and Clover Vaccines. His employer Murdoch Children’s Research Institute is compensated for his time. A. Greinacher reports grants and non-financial support from Aspen, Boehringer Ingelheim, MSD, Bristol Myers Squibb (BMS), Paringenix, Bayer Healthcare, Gore Inc., Rovi, Sagent, Biomarin/Prosensa, personal fees from Aspen, Boehringer Ingelheim, MSD, Macopharma, BMS, Chromatec, Werfen, nonfinancial support from Boehringer Ingelheim, Portola, Ergomed, GTH e.V. outside the submitted work. No other authors report conflicts of interest. Parts of the German results reported have been obtained in a study conducted by Universitätsmedizin Greifswald under service contract No. EMA/2021/17/TDA. The views expressed are the personal views of the authors and may not be understood or quoted as being made on behalf of or reflecting the position of the European Medicines Agency or one of its Committees or Working Parties. The Taiwan VITT case information was based on data provided by the Vaccine Adverse Event Reporting System, operated by Taiwan Centers for Disease Control., (Copyright © 2024 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Background: Immune thrombocytopenic purpura (ITP) is a disease characterized by a decrease in platelet count, which can be triggered by various factors, including viral infections and vaccination. With the widespread vaccination against COVID-19, concerns have arisen regarding a possible link between the vaccine and the exacerbation of ITP. This study aims to comprehensively evaluate the impact of COVID-19 vaccination on ITP patients, including associated risks and outcomes., Methods: A comprehensive search will be conducted in multiple electronic databases (including PubMed, Web of Science, EMBASE, Cochrane Library, CNKI, Wan Fang, VIP, and CBM) to identify relevant studies. This study will include randomized controlled trials, cohort studies, case-control studies, and case series evaluating the impact of COVID-19 vaccination on ITP patients. The primary outcome measure is the change in platelet count, while secondary outcome measures include the occurrence of thromboembolic events, bleeding complications, ITP recurrence rate, impact of ITP exacerbation, and adverse events. Data will be summarized and analyzed using Review Manager Software (RevMan) V.5.4. In addition, subgroup analyses will be performed to explore potential sources of heterogeneity., Results: It is anticipated that different types of COVID-19 vaccines may have varying impacts on ITP patients, leading to potential differences in outcomes. This study aims to comprehensively evaluate the potential impact of COVID-19 vaccination on ITP patients and provide reference for clinical decision-making., Conclusions: The results of this systematic review and meta-analysis will provide crucial information on COVID-19 vaccination for ITP patients and clinicians, contributing to guiding vaccination decisions and monitoring potential impacts after vaccination., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Li et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Immune thrombocytopenia (ITP) is an autoimmune disorder characterized by a low platelet count with increased risk of bleeding, and viral infection may trigger ITP. Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection-induced ITP has been increasingly reported. We systemically reviewed the previously reported cases of SARS-CoV-2 infection-induced ITP and identified a total of 105 patients from 68 studies. The median age was 61 years, and 14 patients (12%) were < 18 years old (pediatric cases). In adult cases, a total of 53% patients were classified as moderate to severe SARS-CoV-2 infection. The median platelet count at diagnosis and nadir were 6,000/µL and 4,000/µL, respectively. When comparing platelet levels between non-severe SARS-CoV-2 infection and moderate to severe SARS-CoV-2 infection, the median values of platelet levels at diagnosis were not significantly different between the groups (4,000/µL in non-severe SARS-CoV-2 infection and 9,000/µL in moderate to severe SARS-CoV-2 infection, p-value = 0.22). Median nadir platelet levels were also not significantly different between groups (4,000/µL in non-severe SARS-CoV-2 infection and 8,000/µL in moderate to severe SARS-CoV-2 infection, p-value = 0.27). More than half of the cases (53 patients) were treated with combination therapy including steroid, intravenous immunoglobulin, and eltrombopag. Major bleeding and intracranial hemorrhage occurred in ten (11%) and six (6.6%) cases, respectively. The overall mortality rate was 7%. In pediatric cases, none of the patients experienced major bleeding and lethal outcomes., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Immune thrombocytopenic purpura (ITP) is an autoimmune disorder, and recent research suggests that gut microbiota and inflammatory cytokines may play a significant role in its pathogenesis. However, the specific effects of these factors on ITP and their relationships remain unclear. We conducted a two-step, two-sample Mendelian randomization study using an inverse variance-weighted approach to investigate the causal role of the gut microbiota in ITP and the mediating effect of inflammatory cytokines on their association. The results showed that among the 473 gut microbiota species, 11 were positively associated and 12 were negatively associated with the risk of ITP. Among the 91 screened inflammatory cytokines, five (CXCL10, CXCL5, IL-12RA, TRAIL, and VEGF-A) were found to have a causal relationship with ITP. Mediation analysis revealed that the gut microbiota UBA1066 promoted the occurrence of ITP through CXCL10 mediation, with a mediation effect of 0.118932 (95% CI: 0.049471-0.188393) accounting for 9.95% of the total effect. Gut microbiota Treponema promoted ITP through VEGF-A mediation, with a mediation effect of 0.045873 (95% CI: 0.01456-0.07718) accounting for 4.28% of the total effect. Gut microbiota Haloplasma promoted the occurrence of ITP via CXCL5. The mediating effect of CXCL5 was 0.038409 (95% CI = 0.00107718-0.07575082), with a mediating ratio of 16.79%. This study revealed a causal relationship between gut microbiota composition and ITP risk, highlighting three inflammatory cytokines as potential causal mediators of this relationship. These findings provide potential targets and biomarkers for the prevention and treatment of ITP with significant clinical implications., (© 2024 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Immune thrombocytopenia (ITP) is an autoimmune bleeding disorder characterized by excessive reticuloendothelial platelet destruction and inadequate compensatory platelet production. However, the pathogenesis of ITP is relatively complex, and its exact mechanisms and etiology have not been definitively established. The gut microbiome, namely a diverse community of symbiotic microorganisms residing in the gastrointestinal system, affects health through involvement in human metabolism, immune modulation, and maintaining physiological balance. Emerging evidence reveals that the gut microbiome composition differs in patients with ITP compared to healthy individuals, which is related with platelet count, disease duration, and response to treatment. These findings suggest that the microbiome and metabolome profiles of individuals could unveil a new pathway for aiding diagnosis, predicting prognosis, assessing treatment response, and formulating personalized therapeutic approaches for ITP. However, due to controversial reports, definitive conclusions cannot be drawn, and further investigations are needed., Competing Interests: Declarations of interest None., (Copyright © 2024. Published by Elsevier Ltd.)

Immune thrombocytopenia (ITP) is a complex autoimmune disorder characterized by thrombocytopenia and an increased bleeding risk, arising from autoantibody-mediated platelet destruction and impaired megakaryocyte function. The pathogenesis of ITP involves a multifaceted interplay of genetic predispositions, immune dysregulation, and environmental triggers, though the precise mechanisms remain uncertain. Several infectious agents, mostly viruses, have been implicated in both acute and chronic ITP through mechanisms such as molecular mimicry, direct bone marrow suppression, and immune dysregulation. Vaccinations, particularly those containing adjuvants like aluminum and those capable of inducing molecular mimicry, have also been associated with ITP, either as a new onset or as a relapse in preexisting cases. The role of drugs, particularly quinine, quinidine and certain antibiotics, in inducing ITP through various immunological pathways further illustrates the diverse etiologies of this condition. The multiple triggers of the disease raise the question of whether ITP may be classified as an autoimmune/inflammatory syndrome induced by adjuvants (ASIA). This condition encompasses a range of autoimmune and inflammatory symptoms triggered by adjuvants, such as silicones, polypropylene meshes, metal implants, and mineral oils present in various medical materials and medications. Similar to that observed in some cases of ITP, adjuvants can trigger autoimmune or autoinflammatory responses via molecular mimicry, epitope spreading, and polyclonal activation. This narrative review explores the underlying environmental factors related to ITP and examines ITP triggers that could potentially support an association between ITP and ASIA syndrome., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024. Published by Elsevier B.V.)

The guinea pig in Ecuador is synonymous with our ancestral gastronomy and cultural tradition, but because of the diet rich in L-canavanine (alfalfa) that they receive; could limit its consumption in patients with primary immune thrombocytopenia (ITP). Ingestion of alfalfa in humans can cause kidney failure and lupus-like syndrome. The John Hopkins Lupus Center recommends avoiding it in the diet of patients with Systemic Lupus Erythematosus (SLE), as it aggravates inflammation by stimulating immune activity (flares). We present two cases of patients with ITP linked to guinea pig ingestion. It is probable, (Universidad Nacional de Córdoba)

A complication of pediatric systemic lupus erythematosus (pSLE) is immune thrombocytopenia (ITP). Although corticosteroids and immunoglobulins are frequently used as preliminary treatments, some patients do not respond to them. Rituximab has been reported to be safe and effective in the treatment of pSLE complicated with refractory ITP. Research is currently underway to determine the optimal rituximab dose for these individuals. We report a case of a child with SLE-associated ITP (SLE-ITP) who was successfully treated with rituximab. Rituximab is likely the most viable therapeutic option for refractory SLE-ITP. Furthermore, a comprehensive review of the relevant literature was performed and a concise overview of the pathogenesis and available treatment modalities for pediatric patients diagnosed with SLE and concurrent ITP was provided., (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Introduction: Immune thrombocytopenia (ITP) is a potentially severe manifestation of systemic lupus erythematosus (SLE) reported in 7-40% of SLE patients. ITP has been associated with a higher risk of organ damage and mortality., Objectives: To describe which factors are associated with the presence of ITP in SLE patients., Methods: Retrospective case-control study. Cases were defined as SLE patients who had ever developed ITP and were sex- and age-matched with two controls. A predictive model was constructed to identify SLE patients who were at risk of developing ITP., Results: ITP prevalence in our SLE cohort was 8.35%. Cases had a higher frequency of hemolytic anemia, while controls had a higher prevalence of arthritis at SLE diagnosis. During SLE progression, cases tested positive for anticardiolipin, anti-β2-glycoprotein 1, and lupus anticoagulant antibodies more frequently. Cases received mycophenolic acid and azathioprine more often than controls and had a higher SLICC/ACR score. The model demonstrated a sensitivity of 87.53%, a positive predictive value of 81.92%, a specificity of 80.50%, area under the curve of 83.92%, a F1 of 83% and an overall accuracy of 83.68%. The variables that best explain the model were hemolytic anemia, arthritis, oral ulcers, Raynaud's phenomenon, low C4, low CH50, anticardiolipin and anti-β2GP1 antibodies., Conclusion: SLE patients who develop ITP have a distinct phenotype characterized by more hemolytic anemia and less arthritis at SLE onset, and higher prevalence of antiphospholipid syndrome antibodies during SLE progression. This phenotype is associated with heightened organ damage and the need for more intensive therapies and stricter follow-up. Our predictive model has demonstrated an impressive ability to identify SLE patients at risk of developing ITP., (Copyright © 2024 Elsevier España, S.L.U. All rights reserved.)

This case illustrates the complex interactions of the immune responses after vaccination and highlights their potential connections to various autoimmune conditions. A 22-year-old man with quiescent ulcerative colitis (UC) presented with abdominal pain, rectal bleeding, and thrombocytopenia 7 days after receiving the third coronavirus disease 2019 mRNA vaccination. Laboratory data confirmed the diagnosis of immune thrombocytopenia. High-dose intravenous immunoglobulin administration boosted the patient's platelet count. Simultaneously, colonoscopy revealed that his UC had relapsed. Although salazosulfapyridine briefly improved his symptoms, his stool frequency worsened one week later. The patient also developed pyoderma gangrenosum. Subsequent treatment with infliximab notably improved both pyoderma gangrenosum and UC.

The management of immune thrombocytopenia (ITP) and the prediction of patient response to therapy still represent a significant and constant challenge in hematology. ITP is a heterogeneous disease with an unpredictable evolution. Although the pathogenesis of ITP is currently better known and its etiology has been extensively studied, up to 75% of adult patients with ITP may develop chronicity, which represents a significant burden on patients' quality of life. A major risk of ITP is bleeding, but knowledge on the exact relationship between the degree of thrombocytopenia and bleeding symptoms, especially at a lower platelet count, is lacking. The actual management of ITP is based on immune suppression (corticosteroids and intravenous immunoglobulins), or the use of thrombopoietin receptor agonists (TPO-RAs), rituximab, or spleen tyrosine kinase (Syk) inhibitors. A better understanding of the underlying pathology has facilitated the development of a number of new targeted therapies (Bruton's tyrosine kinase inhibitors, neonatal Fc receptors, strategies targeting B and plasma cells, strategies targeting T cells, complement inhibitors, and newer TPO-RAs for improving megakaryopoiesis), which seem to be highly effective and well tolerated and result in a significant improvement in patients' quality of life. The disadvantage is that there is a lack of knowledge of the predictive factors of response to treatments, which would help in the development of an optimized treatment algorithm for selected patients.

Background: Splenectomy is commonly used to treat refractory immune-mediated cytopenia, but there are no established factors that are associated with response to the procedure., Objectives: A cohort study was conducted to evaluate the hematologic and surgical outcomes of splenectomy in adult patients with immune cytopenias and identify preoperative factors associated with response., Methods: Data from the Cleveland Clinic Foundation for 1824 patients aged over 18 who underwent splenectomy from 2002 to 2020 were analyzed., Results: The study found that the most common indications for splenectomy were immune thrombocytopenic purpura (ITP) and autoimmune hemolytic anemia, with a median age of 55 years and median time from diagnosis to splenectomy of 11 months. Hematologic response rates were 74% overall, with relapse in 12% of cases. Postsplenectomy discordant diagnoses were present in 13% of patients, associated with higher relapse rates. Surgery-related complications occurred in 12% of cases, whereas only 3% of patients died from disease complications. On univariate analysis, preoperative factors associated with splenectomy treatment failure were ≥3 lines of pharmacologic treatment, whereas isolated thrombocytopenia, primary ITP, and age ≤40 years had a strong association with response. The multivariable regression confirmed that treatment failure with multiple lines of medical therapy was associated with the failure to respond to splenectomy., Conclusion: Overall, the study demonstrates that splenectomy is an effective treatment option for immune-mediated cytopenias with a low complication rate., (© 2023 The Association for the Publication of the Journal of Internal Medicine.)

Introduction: Vaccine-induced immune thrombotic thrombocytopenia (VITT) is a life-threatening prothrombotic disorder first identified following the introduction of adenoviral vector vaccines for COVID-19. The condition is characterized by anti-PF4 antibodies and clinically presents with thrombocytopenia and thrombosis often in unusual anatomical sites., Areas Covered: In this review, we discuss the clinical presentation, diagnostic testing, and treatment of VITT. We also review VITT-like syndromes that have been described in patients without previous vaccination. We propose a conceptual framework for the mechanism of anti-PF4 diseases that includes sufficiently high levels of PF4, the presence of a Polyanion that can form immune complexes with PF4, a Pro-inflammatory milieu, and an immunological Predisposition - the 4Ps., Expert Opinion: Significant progress has been made in understanding the characteristics of the VITT antibody and in testing methods that can confirm that diagnosis. Future work should be directed at understanding long-term outcomes, mechanisms of thrombosis, and individual risk factors for this rare but dangerous immune-thrombotic disease.

To establish pan-European consensus on tapering and discontinuing thrombopoietin receptor agonists (TPO-RAs) in patients with immune thrombocytopenia (ITP), we applied a three-step Delphi technique consisting of a one-to-one interview round and two online survey rounds. Three healthcare professionals (HCPs) from Italy, Spain, and the United Kingdom formed the Steering Committee (SC), which advised on study design, panelist selection, and survey development. A literature review also informed the development of the consensus statements. Likert scales were used to collect quantitative data on panelists' level of agreement. Twelve hematologists representing nine European countries assessed 121 statements spanning three categories: (1) patient selection; (2) tapering and discontinuation strategies; (3) post-discontinuation management. Consensus was reached on approximately half of the statements in each category (32.2%; 44.6%; 66%). Panelists agreed on patients' main selection criteria, patients' involvement in decision-making, tapering strategies, and follow-up criteria. Areas not reaching consensus were risk factors and predictors of successful discontinuation, monitoring intervals, and rates of successful discontinuation or relapse. This lack of consensus signals knowledge and practice gaps among European countries and suggests the need for the development of clinical practice guidelines that outline a pan-European, evidence-based approach to tapering and discontinuing TPO-RAs.

Background: Immune thrombocytopenia (ITP) is an acquired disorder characterised by a low platelet count due to immune-mediated destruction and impaired platelet production. Here we report a rare case of primary cytomegalovirus (CMV) infection followed by thrombocytopenia after renal transplantation (RT)., Case Presentation: A 24-year-old male patient with end-stage kidney disease secondary to hereditary focal segmental glomerulosclerosis was treated with peritoneal dialysis and received ABO-compatible living-related RT from his aunt. Nine months after the RT, the patient was diagnosed with primary CMV infection. After initiating treatment for primary CMV infection, the patient developed thrombocytopenia. After excluding other diseases or drugs that may cause thrombocytopenia, the patient was finally diagnosed with ITP, administered prednisolone (PSL), and started on Helicobacter pylori eradication therapy. Tapering the PSL dose was difficult, but thrombopoietin receptor agonists (TPO-RAs) were effective., Conclusions: In this case, the patient was diagnosed with ITP, and other causes of thrombocytopenia after RT were successfully ruled out. This case report demonstrates that RT recipients can develop ITP after CMV infection, and, in such cases, TPO-RAs may be an attractive option as a second-line therapy., (© 2023. The Author(s).)

Introduction: Childhood immune thrombocytopenic purpura (ITP) is a heterogeneous immune-mediated process triggered by infections, vaccines, allergies and parasites. Currently, there is little evidence in the literature beyond case reports of an association with Toxoplasma gondii (T. gondii)., Methods: The authors describe the unusual case of an earlier healthy 2.5-year-old Greek boy who developed acute ITP with a life-threatening platelet count a few days after a T. gondii infection. Evidence for the infection onset was found incidentally 3 months after the initial admission to the hospital and only after any other plausible cause of thrombocytopenia was excluded, according to diagnosis guidelines., Results: The boy underwent 3 intravenous immunoglobulin treatments within a trimester, a period during which his alarming platelets count levels led to housebound activities. A quite slow recovery was only ignited after the third treatment, which was administered in conjunction with a mild antibiotic medication for the T. gondii infection. Full recovery was obtained 9 months after the initial admission, although the boy's potential scored high in clinical prediction models for developing transient ITP., Conclusion: There is a need for more research on ITPs with no obvious cause to investigate a causal association with toxoplasmosis. Currently, testing for diseases of greater rarity and of higher diagnostic cost than T. gondii is included in the ITP guidelines. Hence, routinely testing for toxoplasmosis when considering potential childhood ITP triggers and infection treatment complementary to treating the ITP might be the key to accelerating the healing process and improving the quality of life of otherwise confined children., Competing Interests: The authors have no funding or conflicts of interest to disclose., (Copyright © 2023 Wolters Kluwer Health, Inc. All rights reserved.)

A subset of individuals with 'primary' or 'idiopathic' immune thrombocytopenia (ITP) who fail to respond to conventional first- and second-line agents or who lose responsiveness are considered to have 'refractory' disease (rITP), placing them at increased risk of bleeding and complications of intensive treatment. However, the criteria used to define the refractory state vary among studies, which complicates research and clinical investigation. Moreover, it is unclear whether rITP is simply 'more severe' ITP, or if there are specific pathogenic pathways that are more likely to result in refractory disease, and whether the presence or development of rITP can be established or anticipated based on these differences. This paper reviews potential biological features that may be associated with rITP, including genetic and epigenetic risk factors, dysregulation of T cells and cytokine networks, antibody affinity and specificity, activation of complement, impaired platelet production and alterations in platelet viability and clearance. These findings indicate the need for longitudinal studies using novel clinically available methodologies to identify and monitor pathogenic T cells, platelet antibodies and other clues to the development of refractory disease., (© 2023 British Society for Haematology and John Wiley & Sons Ltd.)

There are not many publications that provide a holistic view of the management of primary and secondary ITP as a whole, reflecting the similarities and differences between the two. Given the lack of major clinical trials, we believe that comprehensive reviews are much needed to guide the diagnosis and treatment of ITP today. Therefore, our review addresses the contemporary diagnosis and treatment of ITP in adult patients. With respect to primary ITP we especially focus on establishing the management of ITP based on the different and successive lines of treatment. Life-threatening situations, "bridge therapy" to surgery or invasive procedures and refractory ITP are also comprehensively reviewed here. Secondary ITP is studied according to its pathogenesis by establishing three major differential groups: Immune Thrombocytopenia due to Central Defects, Immune Thrombocytopenia due to Blocked Differentiation and Immune Thrombocytopenia due to Defective Peripheral Immune Response. Here we provide an up-to-date snapshot of the current diagnosis and treatment of ITP, including a special interest in addressing rare causes of this disease in our daily clinical practice. The target population of this review is adult patients only and the target audience is medical professionals., Competing Interests: Declaration of Competing Interest Tomás José González-López has received research grants from Amgen and Novartis and speaker honoraria from Amgen, Novartis, Sobi, Grifols and Argenx. Drew Provan has received research support and honoraria from Amgen and Novartis and has acted as a consultant for UCB, MedImmune, Ono and Takeda. Dr. Jarque-Ramos reports consulting honorarium from Amgen, Novartis and Shionogi. Rest of authors declare no competing financial interests., (Copyright © 2023 Elsevier Ltd. All rights reserved.)

Splenectomy remains an effective treatment for refractory immune cytopenia (RIC), which encompasses immune thrombocytopenia (ITP) and autoimmune hemolytic anemia (AIHA). Accessory spleens (AS) have been described without identifying specific risk factors. We retrospectively analyzed patients with RIC after splenectomy who underwent splenic scintigraphy (SS) at our institution. Seventy-one patients were included. Sixty-two patients had ITP, five had AIHA, and four had Evans syndrome. Seventy-five percent (n = 53) were women. Eleven patients (15.5%) had an AS detected by SS. A complete response (CR) to first-line steroids (odds ratio (OR) 5.75, 95% confidence interval (CI) 1.37-24.14, p = 0.017) and the absence of Howell-Jolly bodies (HJB) in peripheral blood smear (PBS) (OR 11.37, 95% CI 2.70-47.85, p = 0.001) were found to be risk factors. Patients with both elements had a higher rate of AS (83.3%) when compared to those with one or no factors (p < 0.001). Eight patients (73%) underwent an accessory splenectomy: seven (87.5%) achieved a CR, and none had perioperative complications. The presence of HJB in PBS changed from 25 to 87.5% after accessory splenectomy. We recommend the search for an AS via SS in patients with RIC due to ITP, who had a CR to corticosteroids and the absence of HJB in PBS. Accessory splenectomy is a safe and effective procedure., (© 2023. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Introduction: Immune thrombocytopenia [ITP] is a common bleeding disorder with an isolated platelet count of less than 100 × 10 9 /L., Areas Covered: Relevant literature from 2003 to 2022 was retrieved and reviewed from the Google Scholar search engine and PubMed database. Antibodies produced by autoreactive B lymphocytes and the phagocytic function of macrophages are considered the most critical factors in platelet destruction. Also, macrophages present the antigen to T lymphocytes and activate them. Follicular helper T-cells [TFH] play a role in stimulating, differentiating, and activating autoreactive B cells, while cluster of differentiation [CD]-8+ T plays a role in platelet destruction through apoptosis. The classical pathway of the complement system also causes platelet destruction. By inhibiting platelet production, low levels of thrombopoietin and an immune response against megakaryocytes in the bone marrow worsen thrombocytopenia., Expert Opinion: T-cell subset changes and an increase in activated autoreactive B cells, in addition to the function of components of the innate immune system [the complement system, dendritic cells, and natural killer cells], play a critical role in the pathogenesis of the ITP. Accurate detection of these changes may lead to developing new therapeutic strategies and identifying better prognostic/diagnostic factors.

Immune thrombocytopenia (ITP) is an autoimmune disease characterized by the breakdown of immune tolerance. Impairment of the cellular immunity is primarily evaluated by the levels of the cytokines which can help in predicting the course of ITP. We aimed to assess the levels of IL4 and IL6 in children with ITP and evaluate their role in the pathogenesis and prognosis of this disease. A prospective cohort study was carried on 60 children (15 patients with newly diagnosed ITP, 15 patients with persistent ITP, 15 patients with chronic ITP and 15 healthy children as a control group). Serum IL-4 and serum IL-6 were measured using Human IL-4 and IL-6 ELISA kit in patients and controls. Patients with newly diagnosed and persistent ITP had significantly higher levels of IL4 and IL6 compared to patients with chronic ITP and healthy controls (p < 0.001). The mean serum level of IL4 was 762.0, 741.0, 364.6 and 436.8 pg/ml, and the mean serum level of IL6 was 178.5, 164.4, 57.9 and 88.4 pg/ml for patients with newly diagnosed, persistent, chronic ITP and healthy controls respectively. Serum IL-4 was significantly higher in patients who achieved remission than those who did not improve on first line therapy., Conclusion: Serum IL-4 and IL-6 may have a role in the pathogenesis of primary ITP. IL-4 seems to be a good predictor to treatment response., What Is Known: • There is a delicate balance of specific cytokine levels in immune thrombocytopenia, which has an important role in the immune system and is known to be deregulated in autoimmune diseases. changes in IL-4 and IL-6 might be involved in the pathogenesis of newly diagnosed ITP in both paediatric and adult patients. • We conducted this research study to measure the serum level of IL-4 and IL-6, in newly diagnosed, persistent and chronic ITP patients and study their relation to disease pathogenesis as well as patient's outcome., What Is New: • We found that IL4 seems to be a good predictor to treatment response and it was a very interesting observation in our study, and to the best of our knowledge, there is no published data about this finding., (© 2023. The Author(s).)

Autoimmune haemolytic anaemia (AIHA) and immune thrombocytopenia (ITP) are two uncommon haematologic autoimmune conditions that can rarely arise secondary to vaccination. Prior studies using the US Centers for Disease Control's (CDC) Vaccine Adverse Event Reporting System (VAERS) have demonstrated this infrequency, but contemporary data as well as comparison with current information regarding SARS-CoV-2 vaccination has not been assessed. In this study, we reviewed VAERS database reports from 1990 to 2022 to characterize the incidence and clinical and laboratory findings of non-SARS-CoV-2-associated AIHA and ITP and SARS-CoV-2 vaccine-associated AIHA and ITP. We discovered a total of 863 AIHA and ITP reports following vaccination with 15 non-SARS-CoV-2 and four SARS-CoV-2 vaccines submitted to the CDC VAERS database. AIHA and ITP reporting was low for both groups, with a large proportion excluded due to a lack of clinical details. ITP was reported the most frequently in both groups and was significantly more common with measles-mumps-rubella (MMR) vaccination (p < 0.001) in the non-SARS-CoV-2 group. AIHA and ITP cases were higher in the SARS-CoV-2 vaccine group, though ultimately still very infrequent. Autoimmune haematologic disease is vanishingly rare after immunization and rates are lower than in the general population according to passive reporting., (© 2022 British Society for Haematology and John Wiley & Sons Ltd.)

The COVID-19 pandemic has had a huge effect all over the world and its impact has been even more profound in the world of Healthcare. In this brief report we'd like to report about our experience in pediatric newly diagnosed thrombocytopenia and how we have seen the landscape of this disease change in the last 2 years. In particular, we believe that the use of personal protective equipment and lockdown measures have reduced the incidence of viral triggers that are supposed to be responsible for the vast majority of ITP cases. Along with these data, we found some other significant differences in the period taken into account.

Purpose: Following the emergency use authorization of BNT162b2 by the Food and Drug administration (FDA) in early December 2020, mRNA- and vector-based vaccines became an important means of reducing the spread and mortality of the COVID-19 pandemic. The European Medicines Agency labelled immune thrombocytopenia (ITP) as a rare adverse reaction of unknown frequency after vector-, but not mRNA-vaccination. Here, we report on the long-term outcome of 6 patients who were diagnosed with de-novo, vaccine-associated ITP (VA-ITP), and on the outcome of subsequent SARS-CoV-2 re-vaccinations., Methods: Patients were included after presenting to our emergency department. Therapy was applied according to ITP guidelines. Follow-up data were obtained from outpatient departments. Both mRNA- or vector-based vaccines were each used in 3 cases, respectively., Results: In all patients, the onset of symptoms occurred after the 1st dose of vaccine was applied. 5 patients required treatment, 3 of them 2nd line therapy. All patients showed a complete response eventually. After up to 359 days of follow-up, 2 patients were still under 2nd line therapy with thrombopoietin receptor agonists. 5 patients have been re-vaccinated with up to 3 consecutive doses of SARS-CoV-2 vaccines, 4 of them showing stable platelet counts hereafter., Conclusion: Thrombocytopenia after COVID-19 vaccination should trigger a diagnostic workup to exclude vaccine-induced immune thrombotic thrombocytopenia (VITT) and, if confirmed, VA-ITP should be treated according to current ITP guidelines. Re-vaccination of patients seems feasible under close monitoring of blood counts and using a vaccine that differs from the one triggering the initial episode of VA-ITP., (© 2022. The Author(s).)

In late February 2021, a prothrombotic syndrome was encountered for the first time in some of the recipients of ChAdOx1 CoV-19 vaccine (AstraZeneca, University of Oxford, and Serum Institute of India). Since the hallmark of this syndrome is the development of thrombocytopenia and/or thrombosis between 4 and 42 days after receiving a COVID-19 vaccine, it was named vaccine-induced immune thrombotic thrombocytopenia (VITT). Other names include "vaccine-induced prothrombotic immune thrombocytopenia" and "thrombosis with thrombocytopenia syndrome" by the Centers for Disease Control and the Food and Drug Administration (FDA). VITT appears similar to heparin-induced thrombocytopenia in that "platelet activating" autoantibodies are produced in both these conditions due to prior exposure of COVID-19 vaccine and heparin respectively, in turn causing thrombotic complications and consumptive thrombocytopenia. In this article, recent advances in the understanding of pathobiology, clinical features, investigative work-up, and management of VITT are reviewed., (© 2022 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Immune thrombocytopenia (ITP) is a common hematological manifestation of systemic lupus erythematosus (SLE). The heterogeneity of its clinical characteristics and therapeutic responses reflects a complex pathogenesis. A better understanding of its pathophysiological mechanisms and employing an optimal treatment regimen is therefore important to improve the response rate and prognosis, and avoid unwanted outcomes. Besides glucocorticoids, traditional immunosuppressants (i.e. cyclosporine, mycophenolate mofetil) and intravenous immunoglobulins, new therapies are emerging and promising for the treatment of intractable SLE-ITP, such as thrombopoietin receptor agonists (TPO-RAs), platelet desialylation inhibitors(i.e. oseltamivir), B-cell targeting therapy(i.e. rituximab, belimumab), neonatal Fc receptor(FcRn) inhibitor, spleen tyrosine kinase(Syk) inhibitor and Bruton tyrosine kinase(BTK) inhibitor et al., although more rigorous randomized controlled trials are needed to substantiate their efficacy. In this review, we update our current knowledge on the pathogenesis and treatment of SLE-ITP., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022 Elsevier Ltd. All rights reserved.)

Autoimmunity linked to COVID-19 immunization has been recorded throughout the pandemic. Herein we present six new patients who experienced relapses of previous autoimmune disease (AD) or developed a new autoimmune or autoinflammatory condition following vaccination. In addition, we documented additional cases through a systematic review of the literature up to August 1st, 2022, in which 464 studies (928 cases) were included. The majority of patients (53.6%) were women, with a median age of 48 years (IQR: 34 to 66). The median period between immunization and the start of symptoms was eight days (IQR: 3 to 14). New-onset conditions were observed in 81.5% (n: 756) of the cases. The most common diseases associated with new-onset events following vaccination were immune thrombocytopenia, myocarditis, and Guillain-Barré syndrome. In contrast, immune thrombocytopenia, psoriasis, IgA nephropathy, and systemic lupus erythematosus were the most common illnesses associated with relapsing episodes (18.5%, n: 172). The first dosage was linked with new-onset events (69.8% vs. 59.3%, P = 0.0100), whereas the second dose was related to relapsing disease (29.5% vs. 59.3%, P = 0.0159). New-onset conditions and relapsing diseases were more common in women (51.5% and 62.9%, respectively; P = 0.0081). The groups were evenly balanced in age. No deaths were recorded after the disease relapsed, while 4.7% of patients with new-onset conditions died (P = 0.0013). In conclusion, there may be an association between COVID-19 vaccination and autoimmune and inflammatory diseases. Some ADs seem to be more common than others. Vaccines and SARS-CoV-2 may induce autoimmunity through similar mechanisms. Large, well-controlled studies are warranted to validate this relationship and assess additional variables such as genetic and other environmental factors., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022 Elsevier Ltd. All rights reserved.)

Thrombopoietin receptor agonists (TPO-RA) are a valid therapy for immune thrombocytopenia (ITP), due to megakaryocyte stimulation and (poorly characterised) immune-modulatory effects. The spleen is pivotal in the pathogenesis of ITP, yet little is known on its immune microenvironment and on effects of TPO-RA on this organ. To address these topics, we analysed 35 spleens removed for primary refractory ITP. Pre-splenectomy TPO-RA administration correlated with increased splenic regulatory T cells (Tregs), type 2 T-helper cells and histiocyte density and with reduced red pulp sinusoids. Surgical outcome was not associated with TPO-RA administration, other pre-splenectomy therapies and/or Treg density. In conclusion, TPO-RA affect the splenic microenvironment, but this has no impact on splenectomy outcome., (© 2022 British Society for Haematology and John Wiley & Sons Ltd.)

Background: The emergence and attendant mortality of vaccine-induced immune thrombocytopenia and thrombosis (VITT) as a consequence of vaccination against severe acute respiratory syndrome coronavirus 2 have resulted in some patients with VITT being considered as deceased organ donors. Outcomes after kidney transplantation in this context are poorly described. Because the disease seems to be mediated by antiplatelet factor 4 antibodies, there is a theoretical risk of transmission via passenger leukocytes within the allograft., Methods: We analyzed the experience of kidney transplantation from donors with VITT in the United Kingdom between January and June 2021. We followed-up all recipients of kidney-only transplants from donors with VITT to detect major postoperative complications or features of disease transmission and assess graft survival and function., Results: There were 16 kidney donors and 30 single kidney transplant recipients in our study period. Of 11 preimplantation biopsies, 4 showed widespread glomerular microthrombi. After a median of 5 mo, patient and graft survival were 97% and 90%, respectively. The median 3-mo estimated glomerular filtration rate was 51 mL/min/1.73 m 2 . Two recipients had detectable antiplatelet factor 4 antibodies but no evidence of clinical disease after transplantation. Major hemorrhagic complications occurred in 3 recipients, all of whom had independent risk factors for bleeding, resulting in the loss of 2 grafts. The involvement of VITT could not be completely excluded in one of these cases., Conclusions: The UK experience to date shows that favorable outcomes are possible after kidney transplantation from donors with VITT but highlights the need for ongoing vigilance for donor-related complications in these patients., Competing Interests: The authors declare no funding or conflicts of interest., (Copyright © 2022 The Author(s). Published by Wolters Kluwer Health, Inc.)

Immune thrombocytopenia (ITP) is the most common acquired thrombocytopenia in children and is caused by immune-mediated decreased platelet production and increased platelet destruction. In the absence of a diagnostic test, ITP must be differentiated from other thrombocytopenic disorders, including inherited platelet disorders. In addition, a diagnosis of secondary ITP due to a primary immune deficiency with immune dysregulation may not be apparent at diagnosis but can alter management and should be considered in an expanding number of clinical scenarios. The diagnostic evaluation of children with thrombocytopenia will vary based on the clinical history and laboratory features. Access to genotyping has broadened the ability to specify the etiology of thrombocytopenia, whereas increasing access to immunophenotyping, functional immunologic and platelet assays, and biochemical markers has allowed for more in-depth evaluation of patients. With this greater availability of testing, diagnostic algorithms in patients with thrombocytopenia have become complex. In this article, we highlight the diagnostic evaluation of thrombocytopenia in children with a focus on ITP, including consideration of underlying genetic and immune disorders, and use hypothetical patient cases to describe disease manifestations and strategies for treatment of pediatric ITP., (© 2022 by The American Society of Hematology.)

Immune thrombocytopenia (ITP) patients are at risk developing to systemic lupus erythematosus (SLE) in the future. Our study attempted to explore the potential risk factors for the development from ITP to SLE in Chinese children by statistical analysis. This study was a retrospective case-control study. Patients diagnosed with ITP and developed to SLE after the diagnosis of ITP were defined as the case group. The control group consisted of children with ITP but without developing to SLE was recruited with a ratio of 1:2. Besides univariable analysis, multivariable logistic regression was built to evaluate the potential risk factors. A total of 150 children was included with 50 in the case group and 100 in the control group. Median developing time from ITP to SLE was 34.5 [IQR 12.5, 58.75] months. ANA was found significantly different between the two groups in our study in the univariable analysis but not in the multivariable analysis (OR = 4.50, 95% CI 0.97 to 21.01). Age diagnosed ITP was positively associated with SLE (OR = 1.07 every 5 years, 95% CI 1.01 to 1.15) with alert point at 8 years old (sensitivity 0.82, specificity 0.60). A lower level of complement was also positively associated with SLE (OR = 8.33, 95% CI 1.62 to 42.91). A minimum 3-year of close follow-up for pediatric ITP patients was recommended to monitor the risk for developing SLE. Older age and hypocomplementemia were potential risk factors for the development from ITP to SLE., (© 2022. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Vaccine-induced immune thrombotic thrombocytopenia (VITT) is a rare complication after severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) adenoviral vector vaccination. In British Columbia (BC), Canada, a provincial clinical care pathway was developed to guide clinicians in evaluating for VITT among patients who present with thrombocytopenia or thrombosis symptoms within 4 to 28 days after adenoviral vector vaccine exposure. All patients had enzyme-linked immunosorbent assay (ELISA) testing for platelet factor 4 (PF4) antibodies, and all cases with positive PF4-ELISA or d-dimer levels ≥2.0 mg/L fibrinogen equivalent units (FEU) had further testing for platelet-activating PF4 antibodies using a modified serotonin release assay (SRA). Between 1 May and 30 June 2021, 37% of 68 patients investigated for VITT had thrombosis, but only 3 had VITT confirmed by PF4-ELISA and SRA. Platelet counts, d-dimer levels, and ELISA optical density values were significantly different between those with and without VITT. Three patients had thrombocytopenia and thrombosis with d-dimer levels >4.0 mg/L FEU but had negative PF4-ELISA and SRA results. Patients with VITT were treated successfully with IV immunoglobulin, nonheparin anticoagulants, and corticosteroids. Our pathway demonstrated that thrombosis is common among patients investigated for VITT and that PF4-ELISA testing is necessary to confirm VITT in those presenting with thrombosis and thrombocytopenia., (© 2022 by The American Society of Hematology. Licensed under Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International (CC BY-NC-ND 4.0), permitting only noncommercial, nonderivative use with attribution. All other rights reserved.)

Objectives: To meta-analyse the clinical manifestations, diagnosis, treatment, and mortality of vaccine-induced immune thrombotic thrombocytopenia (VITT) after adenoviral vector vaccination., Methods: Eighteen studies of VITT after ChAdOx1 nCoV-19 or Ad26.COV2.S vaccine administration were reviewed from PubMed, Scopus, Embase, and Web of Science. The meta-analysis estimated the summary effects and between-study heterogeneity regarding the incidence, manifestations, sites of thrombosis, diagnostic findings, and clinical outcomes., Results: The incidence of total venous thrombosis after ChAdOx1 nCoV-19 vaccination was 28 (95% CI 12-52, I 2 =100%) per 100,000 doses administered. Of 664 patients included in the quantitative analysis (10 studies), the mean age of patients with VITT was 45.6 years (95% CI 43.8-47.4, I 2 =57%), with a female predominance (70%). Cerebral venous thrombosis (CVT), deep vein thrombosis (DVT)/pulmonary thromboembolism (PE), and splanchnic vein thrombosis occurred in 54%, 36%, and 19% of patients with VITT, respectively. The pooled incidence rate of CVT after ChAdOx1 nCoV-19 vaccination (23 per 100,000 person-years) was higher than that reported in the pre-pandemic general population (0.9 per 100,000 person-years). Intracranial haemorrhage and extracranial thrombosis accompanied 47% and 33% of all patients with CVT, respectively. The antiplatelet factor 4 antibody positivity rate was 91% (95% CI 88-94, I 2 =0%) and the overall mortality was 32% (95% CI 24-41, I 2 =69%), and no significant difference was observed between heparin- and non-heparin-based anticoagulation treatments (risk ratio 0.84, 95% CI 0.47-1.50, I 2 =0%)., Conclusions: Patients with VITT after SARS-CoV-2 vaccination most frequently presented with CVT following DVT/PE and splanchnic vein thrombosis, and about one-third of patients had a fatal outcome. This meta-analysis should provide a better understanding of VITT and assist clinicians in identifying VITT early to improve outcomes and optimise management., (Copyright © 2022. Published by Elsevier Ltd.)