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Objectives: To evaluate the effect of idiopathic thrombocytopenic purpura (ITP) on pregnancies and the role of the delta hemoglobin indices in the evaluation of treatment effectiveness. Methods: This case–control study was conducted with 23 ITP and 115 low‐risk pregnancies. Obstetric outcomes (fetal growth retardation (FGR), preterm delivery) and neonatal outcomes (weights, APGAR scores, NICU admissions, thrombocytopenia) were recorded. ITP group was subgrouped based on the platelet ratio at the admission for delivery and evaluated the impact of platelet ratios on blood loss amounts at delivery by using delta hemoglobin indices. Results: Eleven patients received treatment during pregnancy. The gestational age at birth and fetal APGAR scores were lower, and the preterm delivery and FGR rates were higher in the ITP group. Four newborns (17.4%) had thrombocytopenia. There were two postpartum hemorrhages. Newborn platelet counts did not correlate with maternal platelet counts. The study showed no difference in delta hemoglobin counts between the ITP and control groups. Conclusions: ITP is associated with an increased risk of maternal and fetal complications. The presented study showed by using the delta hemoglobin indices that, hemorrhagic complications could be prevented with appropriate management. Neonatal thrombocytopenia should be considered for all ITP patients. [ABSTRACT FROM AUTHOR]

Background. Fixed drug eruption and Rowell syndrome stand as intriguing entities with overlapping clinical and pathological features. Case Presentation. A 32-year-old female patient presented with a tender and pruritic rash on the left upper chest for 3 days. Clinical examination revealed a flaring rash on the chest, under her left eye, tongue, and lips. The patient had a significant past medical history of systemic lupus erythematous with positive (ANA, Sm, dsDNA, ribosomalP, RNP) antibodies, hypocomplementemia, inflammatory arthritis, discoid lupus, leukopenia, thrombocytopenia, and immune thrombocytopenic purpura, and avascular necrosis affecting both hips and her right knee. At the time of presentation, the patient was on azathioprine 150 mg daily and hydroxychloroquine 200 mg twice daily. Skin biopsy of the left upper chest revealed interface dermatitis with necrotic keratinocytes at the dermal-epidermal junction. Superficial and, in some areas, deep perivascular and peri adnexal lymphocytic infiltrates were observed, accompanied by eosinophils. CD123 staining highlighted 16% of the inflammatory cells. Direct Immunofluorescence for IgG, IgA, IgM, C3, and fibrinogen revealed positive linear basement membrane staining for IgG and fibrinogen, with no significant staining for the remaining immunoreactants. Considering the patient's history of medicine usage, and negative SS-A and SS-B antibody, a fixed drug eruption was favored. Discussion. This article discusses the clinical presentations, pathophysiological mechanisms, and diagnostic criteria for fixed drug eruption and Rowell syndrome. Conclusion. Awareness of the distinct clinical and histopathologic features of fixed drug eruption and Rowell syndrome, particularly when sharing cutaneous manifestations, underscores the importance of a comprehensive diagnostic approach and laboratory testing. [ABSTRACT FROM AUTHOR]

Summary Therapies such as corticosteroids, thrombopoietin receptor agonists and immunomodulators have been consistently under the spotlight in the search for a better treatment for immune thrombocytopenia (ITP). However, none of them has been widely embraced as a new standard. In this pilot study, we investigated feasibility, safety and preliminary efficacy of romiplostim, low‐dose rituximab and high‐dose dexamethasone for newly diagnosed ITP. We conducted a single‐centre single‐arm pilot. One‐month treatment adherence was 100%. The 1‐month overall response rate was 92.3%. Complete response occurred in 11 (84.6%) patients. Median duration of response was 4.13 monts (range 0.2–25). No serious adverse events presented. [ABSTRACT FROM AUTHOR]

Altered mechanotransduction has been proposed as a putative mechanism for disease pathophysiology, yet evidence remains scarce. Here we introduce a concept we call single cell immuno-mechanical modulation, which links immunology, integrin biology, cellular mechanics, and disease pathophysiology and symptomology. Using a micropatterned hydrogel-laden coverslip compatible with standard fluorescence microscopy, we conduct a clinical mechanobiology study, specifically focusing on immune thrombocytopenia (ITP), an autoantibody-mediated platelet disorder that currently lacks a reliable biomarker for bleeding risk. We discover that in pediatric ITP patients (n = 53), low single platelet contraction force alone is a "physics-based" biomarker of bleeding (92.3% sensitivity, 90% specificity). Mechanistically, autoantibodies and monoclonal antibodies drive increases and decreases of cell force by stabilizing integrins in different conformations depending on the targeted epitope. Hence, immuno-mechanical modulation demonstrates how antibodies may pathologically alter mechanotransduction to cause clinical symptoms and this phenomenon can be leveraged to control cellular mechanics for research, diagnostic, and therapeutic purposes. Altered mechanotransduction has been proposed as a mechanism for disease pathophysiology, yet evidence remains scarce. Here, the authors show that antibodies from patients with bleeding disorders bind to integrins and modulate platelet cell contraction force, and this correlates with clinical symptoms. [ABSTRACT FROM AUTHOR]

Summary Primary immune thrombocytopenia (ITP) is an antiplatelet‐antibody‐mediated disorder with accelerated platelet clearance and decreased platelet production. Rozanolixizumab, a monoclonal IgG4 anti‐FcRn antibody, blocks IgG recycling and decreases IgG levels. We report efficacy and safety of rozanolixizumab in adults with persistent/chronic ITP in 24‐week phase 3 studies (TP0003; TP0006), and their 52‐week open‐label extension (OLE). Primary end‐point was durable clinically meaningful platelet response (DCMPR) of ≥50 × 109/L for 8/12 weeks during Weeks 13–25 in the double‐blind studies. Operational delays and evolving ITP treatment landscape led the sponsor to terminate these studies early; thus, only 21 and 12 (TP0003) and 20 and 10 (TP0006) patients were randomised to rozanolixizumab or placebo. Forty‐three patients enrolled in the OLE: 42 started on every 2‐week dosing; 21 later switched to weekly dosing. More rozanolixizumab‐treated than placebo‐treated patients achieved DCMPR: 4/21 versus 0 (TP0003) and 1/20 versus 0 (TP0006). Platelet increases to ≥50 × 109/L were observed on Day 8 in 52.4% (TP0003; 2/12 placebo) and 45.0% (TP0006; 1/10 placebo) of rozanolixizumab‐treated patients. OLE platelet increases were maintained while on weekly dosing. The most frequent treatment‐emergent adverse events overall were headache, pyrexia and nausea, as seen previously. Weekly dosing appears more efficacious than every 2‐week dosing. [ABSTRACT FROM AUTHOR]

ABSTRACT Objectives Methods Results Conclusions Systematic Review Registration Evidence‐based protocols for managing bleeding emergencies in patients with immune thrombocytopenia (ITP) are lacking. We conducted a systematic review of treatments for critical bleeding in patients with ITP.We included all study designs and extracted data in aggregate or individually for patients who received one or more interventions and for whom any of the following outcomes were reported: platelet count response, bleeding, disability, or death.We identified 49 eligible studies reporting 112 critical bleed patients with ITP, including 66 children (median age, 10 years), 36 adults (median age, 41.5 years), and 10 patients with unreported age. Patients received corticosteroids (n = 67), IVIG (n = 49), platelet transfusions (n = 41), TPO‐RAs (n = 17), and splenectomy (n = 28) either alone or in combination. Studies reported 29 different treatment combinations, the 5 most common were corticosteroids, platelet transfusion and splenectomy (n = 13), corticosteroids and IVIG (n = 13), or splenectomy alone (n = 13); IVIG alone (n = 11); and corticosteroids, IVIG and TPO‐RA (n = 8). Mortality among patients with critical bleeds in ITP was 30.6% for adults and 19.7% for children.The effects of individual treatments on patient outcomes were uncertain due to very low‐quality evidence. There is a need for a standardized approach to the treatment of ITP critical bleeds.CRD42020161206. [ABSTRACT FROM AUTHOR]

The pathogenesis of immune thrombocytopenia (ITP) is complex and involves the dysregulation of immune cells, such as T and B lymphocytes, and several cytokines that promote the production of autoantibodies. In the context of cancer patients, ITP can occur in both primary and secondary forms related to anticancer therapies or the disease itself. Objective: In light of these data, we decided to prepare a literature review that will explain the classification and immunological determinants of the pathogenesis of ITP and present the clinical implications of this condition, especially in patients with cancer. Materials and methods: We reviewed the literature on immunological mechanisms, therapies, and challenges in treating ITP, particularly on cancer patients. Results: The results of the literature review show that ITP in cancer patients can be both primary and secondary, with secondary ITP being more often associated with anticancer therapies such as chemotherapy and immunotherapy. Innovative therapies such as TPO-RA, rituximab, Bruton's kinase inhibitors, and FcRn receptor inhibitors have shown promising results in treating refractory ITP, especially in patients with chronic disease. Conclusions: ITP is a significant clinical challenge, especially in the context of oncology patients, where both the disease and treatment can worsen thrombocytopenia and increase the risk of bleeding complications. Treatment of oncology patients with ITP requires an individualized approach, and new therapies offer effective tools for managing this condition. Future research into immunological mechanisms may bring further advances in treating ITP and improve outcomes in cancer patients. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Understanding platelet protein functions facilitates better assessment of platelet disorders. Megakaryocyte lineage-restricted human Disabled-2 knock-in (hDAB2-KI) mice are generated to delineate the functions of hDab2, a regulator of platelet function, in the control of bleeding associated with thrombocytopenia. Here we show that hDab2-KI mice with thrombocytopenia display decreased bleeding time when compared to the control mice. hDab2 augments thromboxane A2 (TxA2) mimetic U46619- but not other agonists-stimulated granule secretion, integrin activation, and aggregation at a lower platelet concentration in vitro. Binding of hDab2 to phosphatidic acid (PA) facilitates formation of the PA-hDab2-AKT complex leading to an increase in U46619-stimulated AKT-Ser473 phosphorylation and the first wave of ADP/ATP release. Consistent with these findings, hDab2 expression in platelets from patients with immune thrombocytopenic purpura is positively correlated with U46619-stimulated ATP release, which in turn inversely correlated with their bleeding tendency. hDab2 appears crucial in regulating bleeding severity associated with thrombocytopenia by a functional interplay with ADP/ATP release underlying TxA2 signaling. Human Disabled-2 (hDab2) is a key regulator of bleeding severity associated with thrombocytopenia. Here the authors show this is facilitated by the functional interplays of hDab2 with phosphatidic acid, AKT, and ADP/ATP release underlying thromboxane A2 signaling. [ABSTRACT FROM AUTHOR]

Background: Primary immune thrombocytopenia (ITP) is an immune-mediated hematologic disorder characterized by a reduction in platelet count, increasing the risk of bleeding. Recent studies have indicated a close association between alterations in gut microbiota and the development of ITP. However, the mechanisms by which gut microbiota influence the occurrence and progression of ITP through plasma metabolites remain poorly understood. Evidence suggests extensive interactions between gut microbiota and plasma metabolites, implying a potential role for gut microbiota in influencing ITP through alterations in plasma metabolites, which requires further investigation. Methods: In this study, summarized GWAS data (including 211 gut microbiota taxa, 1,400 plasma metabolites or ratios, and an ITP patient cohort) were retrieved from the MiBioGen and GWAS Catalog databases. Using a two-sample Mendelian randomization (MR) approach, we screened gut microbiota and plasma metabolites potentially causally related to ITP. We further identified plasma metabolites serving as mediators through which gut microbiota affect ITP and calculated the strength of the mediation effect. To ensure result stability, we primarily used the inverse variance weighted (IVW) method as the main judgment index. We also utilized MR Egger and inverse variance weighted methods to detect heterogeneity in the results, and employed MR-Egger and MR-PRESSO methods to assess the presence of pleiotropy. Results: Though two-sample MR analysis, 8 gut microbiota taxa were found to have causal relationships with ITP. After excluding six plasma metabolites with pleiotropy, 39 plasma metabolites were found to be causally related to ITP (P < 0.05). Eleven plasma metabolites were identified as having causal relationships between gut microbiota and plasma metabolites. Finally, using the delta method, it was calculated that Sphingomyelin levels (8.0%, 95%CI: 0.9% to 11.5%, P = 0.047) and Glucose-to-mannose ratio (6.5%, 95%CI: 0.7% to 9.5%, P = 0.039) are intermediates for Intestinimonas influencing ITP, while Bilirubin (Z,Z) to etiocholanolone glucuronide ratio (5.6%, 95%CI: 4.7% to 6.9%, P = 0.043) is an intermediate for Senegalimassilia influencing ITP. Conclusion: Gut microbiota can influence the development of ITP through changes in plasma metabolites. Sphingomyelin levels, Glucose-to-mannose ratio, and Bilirubin (Z,Z) to etiocholanolone glucuronide ratio are newly discovered intermediates through which gut microbiota influence ITP, providing potential indicators and targets for clinical diagnosis and treatment. This study highlights the intricate relationship between gut microbiota and plasma metabolites in the context of ITP, suggesting new avenues for clinical diagnosis and treatment. [ABSTRACT FROM AUTHOR]

Background Study Design and Methods Results Conclusion The characteristic feature of immune cytopenias involves the process of extravascular phagocytosis, wherein macrophages in the spleen and/or liver engage in the destruction of blood cells that have been opsonized by auto‐ or alloantibodies. Therefore, new treatments that prevent phagocytosis will be advantageous, especially for short‐term usage along with alternative options.KB‐208, a small molecule drug, previously shown to be efficacious for the in vitro inhibition of phagocytosis was synthesized. A passive antibody mouse model of immune thrombocytopenia (ITP) was used. Three different mouse strains (BALB/c, C57BL/6, CD1) were used to determine the efficacy of KB‐208 compared with IVIG to ameliorate the ITP. Toxicity was investigated after 60‐day chronic administration of KB‐208 by a biochemistry panel, gross necroscopy and histopathology.KB‐208 showed similar efficacy to ameliorate the thrombocytopenia compared with IVIG in all three mouse strains. This small molecule drug was effective at 1 mg/kg in ameliorating ITP, in comparison with IVIG at 1000–2500 mg/kg. KB‐208 did not affect other blood parameters or elevate serum biochemistry markers of toxicity nor were any abnormal histopathological findings found.KB‐208 is similar to IVIG for the amelioration of ITP in multiple mouse strains. Chronic administration of KB‐208 for 60 days did not demonstrate in vivo toxicity. These findings indicate that KB‐208 is efficacious, without significant in vivo toxicities in mice, and is a potential small molecule candidate for further evaluation to be used in the treatment of ITP and possibly all immune cytopenias where phagocytosis is responsible for the pathophysiology. [ABSTRACT FROM AUTHOR]

ABSTRACT Objective Methods Results Conclusions 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. [ABSTRACT FROM AUTHOR]

Key Clinical Massage: Tubo‐ovarian abscess (TOA) is a serious health hazard for women, causing severe sepsis. Antimicrobial treatment is effective, but one‐third of patients experience unfavorable outcomes. ITP, an autoimmune condition, can lead to bruising and bleeding. Diagnosing TOA in women of childbearing age is crucial, and combining emergency surgery with ITP patients can increase treatment costs and reduce quality of life. ITP can lead to severe complications, including postoperative hemorrhage, and may require platelet transfusions, glucocorticosteroids, and immunoglobulin. These treatments increase costs, decrease quality of life, and impact prognosis. Preventing ITP is crucial. Patients should be administered blood products based on platelet count and anemia or spontaneous bleeding tendencies. Perioperative blood management should aim for a target platelet level of 30 × 109/L and a hemoglobin concentration of 80 g/L before surgery. Post‐surgery, perioperative care is crucial and vigilant for secondary bleeding. A tubo‐ovarian abscess (TOA) is a frequently encountered inflammatory mass in therapeutic settings. TOA is a serious consequence of pelvic inflammatory disease (PID) that can lead to severe sepsis. In recent years, the incidence of TOA has increased, presenting a significant health hazard for women. To effectively target the diverse range of bacteria responsible for TOA, it is essential to use antimicrobial medicines that have a wide spectrum of activity. Nevertheless, the efficacy of antibiotic treatment stands at approximately 70%, while a significant proportion of patients, around one‐third, experience unfavorable clinical outcomes necessitating drainage or surgical intervention. Immune thrombocytopenia (ITP) is an autoimmune condition characterized by a marked decrease in the quantity of platelets present in the bloodstream. ITP is characterized by thrombocytopenia, which leads to a heightened susceptibility to bruising and bleeding. The diagnosis of ITP and the prediction of treatment response continue to pose important and persistent issues in the field of hematology. The platelet count is commonly employed as a surrogate indicator of disease severity in patients with ITP and thus plays a crucial role in determining the necessity of treatment. A 25‐year‐old woman with a history of sexual activity underwent open abdominal exploration due to the sudden onset of lower abdominal pain. During the operation, a left TOA was discovered, and an incision and drainage were performed. Symptomatic treatments, such as anti‐infectives and abdominal drainage, were administered. The culture of pus in the abdominal cavity suggested the presence of Escherichia coli. However, the patient presented with ITP and had a platelet count of less than 50 × 109/L before the operation. After the operation, the patient developed incisional and pelvic hematomas with signs of infection. As a result, the patient was discharged from the hospital after undergoing another laparotomy and receiving platelet transfusions and immunotherapy. Clinicians should be vigilant when diagnosing TOA in women of childbearing age, even in the absence of high‐risk factors. A timely antibiotic or surgical intervention is necessary to preserve fertility and ensure quality of life. Combining emergency surgery with ITP patients poses a significant challenge for clinicians in terms of treatment. ITP can lead to serious complications, such as postoperative bleeding, which may require platelet transfusions, glucocorticoids, and immunoglobulin. This can increase the cost of treatment, reduce the quality of life, and seriously affect the prognosis. Therefore, preventing ITP is crucial. It is important to pay attention to the perioperative care of patients after surgery and be alert to the possibility of secondary hemorrhage. [ABSTRACT FROM AUTHOR]

Immune thrombocytopenic purpura (ITP) affects 1–3 out of every 10 000 pregnancies, posing significant risks to both mothers and newborns. The condition often requires careful management to prevent severe hemorrhagic events. PubMed, Embase, Scopus, and Web of Science searched for relevant literature until June 2024. A meta‐analysis was performed to evaluate the effect of ITP on maternal and fetal outcomes. The results showed that antepartum hemorrhage occurred in 0.17 (95% CI = 0.12–0.25) of patients and postpartum hemorrhage occurred in 0.11 (95% CI = 0.07–0.16) of pregnant women with ITP. About 0.63 (95% CI = 0.50–0.74) of pregnant women needed treatment for ITP. The cesarean section (CS) rate was 0.48 (95% CI = 0.34–0.61), and the occurrence of preterm labor was 0.14 (95% CI = 0.07–0.24). A total of 0.32 of neonates had thrombocytopenia (95% CI = 0.18–0.52). The difference between the platelet count of those diagnosed with ITP before pregnancy and those diagnosed after pregnancy was significant (MD = –31.50, 95% CI = 51.29–11.72, p < 0.01). This meta‐analysis highlights the significant impact of ITP on pregnancy, estimating risks of bleeding, CS, gestational diabetes, preterm labor, and neonatal thrombocytopenia. These findings underscore the need for vigilant monitoring and tailored management of pregnant women with ITP. [ABSTRACT FROM AUTHOR]

Summary: Primary immune thrombocytopenia (ITP) is an autoimmune bleeding disorder, and chemokines have been shown to be dysregulated in autoimmune disorders. We conducted a prospective analysis to identify potential chemokines that could enhance the diagnostic accuracy and bleeding evaluation in ITP patients. In the discovery cohort, a Luminex‐based assay was employed to quantify concentrations of plasma multiple chemokines. These levels were subjected to comparative analysis using a cohort of 60 ITP patients and 17 patients with thrombocytopenia other than ITP (non‐ITP). Additionally, comparative evaluation was conducted between a subgroup of 12 ITP patients characterised by bleeding episodes (ITP‐B, as defined by an ITP‐2016 bleeding grade ≥2) and 33 ITP patients without bleeding episodes (ITP‐NB, as defined by an ITP‐2016 bleeding grade ≤1). Machine learning algorithms further identified CCL20, interleukin‐2, CCL26, CCL25, and CXCL1 as promising indicators for accurate diagnosis of ITP and CCL21, CXCL8, CXCL10, CCL8, CCL3, and CCL15 as biomarkers for assessing bleeding risk in ITP patients. The results were confirmed using enzyme‐linked immunosorbent assays in a validation cohort (43 ITP patients and 19 non‐ITP patients). Overall, the findings suggest that specific chemokines show promise as potential biomarkers for diagnosis and bleeding evaluation in ITP patients. [ABSTRACT FROM AUTHOR]

Summary: There are variations in individual eltrombopag concentrations that may impact efficacy and adverse drug reactions (ADRs) in paediatric immune thrombocytopenia (ITP). To solve this problem, we tailored the eltrombopag dosage refer to concentration, then followed up to assess concentration value in paediatric ITP. This is a single‐centre, prospective, observational study. The eltrombopag dosage was adjusted, and children were divided into three groups: the maintenance, discontinuation, and increase groups. Concentration and other data were compared to explore concentration value in guiding the individualized treatment of paediatric ITP. Thirty‐nine patients were enrolled, including 23 in the maintenance group, 3 in the discontinued group and 13 in the increase group. 3 patients discontinued eltrombopag due to ADRs, which was significantly higher than patients in the maintenance group (t = 3.606, p = 0.001). In all, 13 patients increased their dosage due to poor response, whose concentration and platelet count were significantly lower than patients in the maintenance group (t = 2.461, p = 0.019; t = 4.633, p < 0.001). Two months after the increase, the number of patients reaching CR and R respectively increased by 2 and 3, while the median platelet count was significantly raised (Z = −2.411, p = 0.016). Concentration could be used as a reference index for the individualized treatment of eltrombopag in paediatric ITP. [ABSTRACT FROM AUTHOR]

Summary: To use proteomic techniques to identify sensitive diagnostic biomarkers for paediatric immune thrombocytopenia (ITP). We selected children in ITP and control groups, using a four‐dimensional data‐independent acquisition approach (4D‐DIA) to analyse its protein expression. The significantly differentially expressed proteins were selected for enzyme‐linked immunosorbent assay (ELISA) validation in a cohort comprising 50 samples (13 healthy controls, 15 secondary thrombocytopenia controls and 22 children with ITP). Receiver operating characteristics (ROC) were generated to diagnose ITP and to assess the diagnostic effectiveness of this approach. Compared with the control group, 55 differentially expressed proteins (43 increased and 12 decreased) were determined in the ITP group. Matrix metalloproteinases‐9 (MMP‐9) and thrombospondin‐1 (THBS1) were significantly expressed and selected for ELISA. The verification outcomes aligned with the findings from the proteomic examinations. In contrast to the control cohort, the ITP subjects exhibited markedly elevated plasma MMP‐9 levels and reduced plasma THBS1 concentrations. Additionally, the ROC curves indicated the diagnostic value of these biomarkers. In conclusion, proteomics facilitates identifying the sensitive biomarkers for ITP diagnosis. We have preliminarily selected two differentially expressed proteins, MMP‐9 and THBS1, whose potential role as biomarkers for diagnosing ITP requires further research. [ABSTRACT FROM AUTHOR]

The article in Clinical & Experimental Dermatology presents a retrospective study of adult patients with Parry–Romberg syndrome (PRS), a rare variant of morphoea. The study reviewed the diagnosis, clinical course, and management of 10 adult patients with PRS, highlighting the importance of early diagnosis and treatment to prevent functional impairment and tissue damage. The majority of patients were women, White, and non-Hispanic, with a significant delay between disease onset and diagnosis. Treatment modalities included immunosuppressive treatments and surgical and cosmetic interventions, with most patients showing improvement or stability with systemic treatment. Further research is needed to better understand this rare condition in the adult population. [Extracted from the article]

Background/Objectives: Immune thrombotic thrombocytopenic purpura (iTTP) is a thrombotic microangiopathy caused by the formation of anti-ADAMTS13 antibodies. Caplacizumab is approved for the treatment of acute episodes of iTTP in conjunction with plasma exchange (PEX) and immunosuppression. Real-world data for the use of caplacizumab in Italy have been recently published by a limited number of centers located in the northern and middle regions of the country only. Methods: A total of 38 patients with iTTP were enrolled in the study in six Italian centers spread over the entire territory of the country. The patients' data were registered in eCRF. Results: All patients achieved normalization of platelet count (median 2.0 days, IQR: 2–4), within a time significantly shorter than in the absence of caplacizumab, as previously reported in other studies. As to the secondary aims, patients treated with caplacizumab had a few exacerbations (4/38 (10.5%)) and relapses (2/38, 5.3%). No deaths or refractoriness were observed in these patients. The total length of hospitalization was 12 days (IQR: 9–18) and only one patient required 2 days of stay in the intensive care unit. Interestingly, when caplacizumab was initiated within the first 3 days, the plasma exchange (PEX) duration was 9 days (IQR: 8–10), which was significantly lower than those reported in previous studies conducted in the absence of caplacizumab. No severe adverse event was described in the caplacizumab-treated patients. Conclusions: Caplacizumab reduced exacerbations and refractoriness compared with previously reported standard-of-care regimens. When administered in association with PEX and immunosuppressive therapy, caplacizumab provided rapid normalization of platelet count, which was responsible for lower overall hospitalization time, ICU stay, lower exacerbations and relapses compared to previously reported outcomes of studies carried out without caplacizumab. [ABSTRACT FROM AUTHOR]

Background: Managing primary immune thrombocytopenia (ITP) in pregnancy is challenging. Providers must balance bleeding risk against medication toxicity. The evaluation of the implementation of pregnancy-specific ITP clinical guidelines has not been widely studied. The goal of this study was to describe the implementation of pregnancy-specific ITP guidelines at an academic health center. Methods: We conducted a retrospective chart review at the University of Oklahoma Health system from 2011 to 2020. Descriptive statistics were calculated to summarize the characteristics of the study population. Management, according to the clinical guidelines (American Society of Hematology; American College of Obstetricians and Gynecologists) was evaluated during pregnancy and during/for delivery. Results: A total of 85 pregnant persons with ITP were included. The majority (68%; 58/85) delivered vaginally. There were 0 maternal deaths and 2 infant deaths. No patients had major bleeding during pregnancy. Postpartum hemorrhage was experienced by 14%. The management of thrombocytopenia during pregnancy was 100% adherent to the strong recommendation for severe (n = 13) and mild (n = 11) thrombocytopenia. However, 18/50 (36%) asymptomatic persons with moderate thrombocytopenia received treatment despite the strong recommendation that treatment was unnecessary. Additionally, 8/21 (38%) persons with moderate thrombocytopenia received treatment to increase platelet counts for epidural anesthesia despite the guideline's suggestion that it was unnecessary. Conclusions: During pregnancy, patients with severe thrombocytopenia (i.e., most at risk of bleeding) received treatment. On the other hand, approximately 40% of pregnant persons with ITP received unnecessary treatment for moderate asymptomatic thrombocytopenia either during pregnancy or for an epidural. Utilizing clinical practice guidelines would reduce the overtreatment of pregnant persons which would reduce the potential side effects of therapy for the mother and infant. [ABSTRACT FROM AUTHOR]

Background/objectives: Fostamatinib is a spleen tyrosine kinase (SYK) inhibitor approved for the treatment of adult patients with chronic immune thrombocytopenia (ITP). There is little information about dose tapering and sustained remission after discontinuation in ITP. In this retrospective multicenter study, we evaluated efficacy and safety of fostamatinib in adult patients with ITP before, during, and after tapering/discontinuation (T/D). Methods: T/D was performed on subjects who achieved complete platelet response (CR) with progressive, conditional dose reduction every four weeks. Results: Sixty-one patients were included from 14 reference centers between October 2021 and May 2023. In subjects that completed T/D (n = 9), the median time from treatment initiation to response was 21 days (IQR: 7.5–42), median time from treatment initiation to CR was 28 days (IQR: 28–42), median time from treatment initiation to the start of tapering was 116 days (IQR: 42–140), and duration of tapering was 112.5 days (IQR: 94.5–191). The median platelet count was 232 × 109/L (IQR: 152–345 × 109/L) at tapering and 190 × 109/L (IQR: 142.5–316.5 × 109/L) at discontinuation. With a median follow-up since discontinuation of 263 days (IQR: 247–313 days), only two patients have relapsed (at 63 and 73 days). Fostamatinib was restarted, achieving a new CR. Platelet counts higher than 100 × 109/L in week 12 were the only positive predictive factors for successful tapering and discontinuation. Conclusions: Sustained response in patient with ITP treated with fostamatinib could be developed. The prognostic factors and recommended scheme of tapering still have to be evaluated. [ABSTRACT FROM AUTHOR]

The article discusses a case study of a 26-year-old female patient with anetoderma, initially presenting as leprosy due to prolonged steroid use. The patient had asymptomatic oval and saccular papules and plaques on her upper limbs, with histopathological evidence confirming indeterminate leprosy. The study highlights the challenges of diagnosing leprosy in patients with prolonged steroid use and emphasizes the importance of a comprehensive diagnostic approach and pharmacovigilance in endemic areas. [Extracted from the article]

Introduction: Inborn errors of immunity (IEIs) are rare genetic disorders primarily identified in children due to their significant effects on immune system functionality. However, an increasing number of IEI cases are being diagnosed in adults, attributed to delayed presentation or advancements in diagnostic capabilities. This study explores the clinical and immunologic distinctions between IEIs diagnosed in adulthood versus childhood, shedding light on their differential presentations, the impact of diagnostic delays, and treatment outcomes. Methods: This study focused on 122 adult patients with IEI above 17 years old, diagnosed in adulthood or childhood. We collected comprehensive data on demographics, clinical presentations, genetic mutations, and therapeutic interventions. Results: The study revealed that 72.9% of participants were diagnosed in adulthood, facing a median diagnostic delay of 96 months. Diagnostic delays were longer in adults (132 months vs. 24 months) than in children. The most common clinical manifestations at onset were recurrent infections (46.7%) and autoimmunity (18%). Predominantly antibody deficiency was the most frequently diagnosed immunodeficiency (54.9%), followed by immunodysregulation at a rate of 26.2%. A higher incidence of immune thrombocytopenia or other complications, such as hepatomegaly and enteropathy, was observed in adult-diagnosed patients with IEI. Malignancies were more prevalent in patients with adult-onset IEI compared to those with childhood-onset (18.1% vs. 5.2%). Overall, 15 different malignancies were recorded in 13 patients (10.6%), including lymphomas and cancers of the stomach, thymus, skin, breast, and colon. Conclusions: The findings highlight a considerable diagnostic delay in recognizing IEI, especially in adults, and illustrate distinct differences in disease manifestation and progression between adult-onset and delayed-diagnosis groups. [ABSTRACT FROM AUTHOR]

Cytotoxic T-lymphocyte associated antigen-4 (CTLA-4) is a costimulatory receptor exhibiting a potent inhibitory signal on antigen-activated immune responses. A soluble form, sCTLA-4, has been identified and was found to be increased in several autoimmune diseases. We aimed to evaluate serum levels of sCTLA-4 in different immune cytopenias, and to determine its possible relation to the disease activity. We measured serum levels of sCTLA-4 in 47 patients with immune cytopenias and compared them to 47 age- and sex-matched healthy controls. sCTLA-4 levels were significantly higher in patients with immune cytopenias compared to healthy controls (p < 0.001), however, levels were comparable between different groups of immune cytopenias (p = 0.084). Serum sCTLA-4 inversely correlated with age at diagnosis and hemoglobin level (p = 0.048, and p = 0.039 respectively), while it directly correlated with disease duration (p = 0.023) as well as markers of hemolysis including reticulocyte count, serum LDH and indirect bilirubin (p = 0.025; p = 0.019; p = 0.004 respectively). In the AIHA group, serum sCTLA-4 levels were significantly lower in patients in remission compared to patients with active disease (p = 0.026). Children with immune cytopenia exhibit significantly higher levels of circulating sCTLA-4 which correlated with disease activity, yet the prognostic significance and its use to tailor treatment regimen require additional studies. [ABSTRACT FROM AUTHOR]

Persistent thrombocytopenia is caused by various diseases, including immune thrombocytopenia, inherited thrombocytopenia, and inherited bone marrow failure syndromes. Considering the large number of genes responsible for inherited disorders, comprehensive genetic analysis is required to diagnose monogenic disorders. In this study, we enrolled 53 pediatric patients with persistent thrombocytopenia exhibiting visually small or normal-sized platelets. We performed whole-exome sequencing, including 56 genes responsible for inherited thrombocytopenia, and evaluated clinical parameters according to disease type. Among 53 patients, 12 patients (22.6%) were diagnosed with monogenic disorders. Nine patients had a family history of thrombocytopenia. Pathogenic or novel variants of genes responsible for inherited thrombocytopenia were identified in three and six patients, respectively. The variants in genes for inherited thrombocytopenia with large or giant platelets were unexpectedly identified in six patients. Pathogenic variants in genes for inherited bone marrow failure syndromes with systemic features were identified in three patients with atypical symptoms. Since the definitive diagnostic methods for immune thrombocytopenia are limited, and a substantial number of patients with inherited thrombocytopenia are at a high risk of developing malignancies, comprehensive genetic analysis is indispensable for selecting appropriate therapies, avoidance of unnecessary treatments for immune thrombocytopenia, and long-term follow-up of patients with inherited thrombocytopenia. [ABSTRACT FROM AUTHOR]

Several international registries have reported on the efficacy of caplacizumab for the treatment of immune thrombotic thrombocytopenic purpura (iTTP). Similar real-world data from the United States (US) are limited. In this single center retrospective study, we sought to describe caplacizumab prescribing patterns and review clinical outcomes for US patients with iTTP. Subjects were eligible for inclusion if they were diagnosed with acute iTTP and received care at University of Pittsburgh Medical Center-affiliated hospitals from 2012 to 2022. Subjects were divided into an historical cohort who received standard of care therapy alone, and early and late administration cohorts (EA and LA) who received caplacizumab within and greater than 72 h of admission, respectively, plus standard of care. Clinical data were collected from the electronic record. Thirty-two subjects were included: 16 historical, 12 EA, and 4 LA subjects. Refractoriness occurred more frequently in the LA and historical cohorts as compared to the EA cohort (4 (100%) vs. 6 (38%) vs. 3 (25%), p = 0.02). The LA cohort also experienced longer lengths of hospital stay, required more TPE procedures, and were exposed to the greatest amount of donor plasma (p < 0.05 for all) as compared to the other cohorts. Time to platelet count normalization was longest in the LA cohort (p = 0.013). There were no significant between-group differences in bleeding events. Because we are unable to predict which patients will develop refractoriness, we recommend frontline administration of caplacizumab to all patients with iTTP. [ABSTRACT FROM AUTHOR]

Eltrombopag, a nonpeptide thrombopoietin receptor agonist, is primarily used for treating immune thrombocytopenic purpura. The aim of this study was to investigate the pharmacokinetic profile and food‐drug interaction of test and reference eltrombopag olamine tablets among healthy Chinese volunteers. An open, randomized, single‐dose, 2‐period crossover design was employed, involving fasting and fed conditions with a 10‐day washout period. Ninety‐six healthy volunteers received a single oral dose of 25 mg of the 2 eltrombopag formulations, with 48 participants in each group: fasting volunteers and those consuming a high‐fat, low‐calcium meal. Plasma eltrombopag concentrations were analyzed using liquid chromatography‐tandem mass spectrometry, and pharmacokinetic parameters were derived from the concentration‐time profiles. The geometric mean ratios, with 90% confidence intervals, for the maximum plasma concentration, area under the concentration‐time curve from time 0 to the last measurable concentration, and area under the concentration‐time curve from time 0 to infinity fell within the bioequivalence acceptance criteria (80%‐125%) under both fasting and fed conditions, indicating bioequivalence between the test and reference formulations. Administration of eltrombopag with a high‐fat, low‐calcium diet reduced the net systemic exposure by approximately 40%. Adverse events were recorded, and no serious adverse events were observed in either fasting or fed conditions. In conclusion, eltrombopag is well tolerated and exhibits a favorable safety profile in the Chinese population. The achievement of bioequivalence under fasting and fed conditions supports the demonstration of biosimilarity between the test and reference formulations. [ABSTRACT FROM AUTHOR]

Background: Primary Immune Thrombocytopenic Purpura (ITP) is an autoimmune hematological condition characterized by isolated thrombocytopenia and frequently presents with oral manifestations. However, reports of primary ITP in patients with Turner Syndrome (TS) are exceptionally rare, with few cases documented in the literature. Herein, we describe an unusual case of primary ITP with exuberant oral manifestations in a patient with TS. Case report: A 29‐year‐old woman was referred to an oral diagnostic service with complaints of "blood blisters and gum bleeding" lasting 8 h. On extraoral physical examination, multiple petechiae were observed in the upper and lower limbs, in addition to hemorrhagic extravasation in the right ocular sclera (hyposphagma). On intraoral examination, multiple vesicles and blisters filled with blood were identified on the lower lip, back of the tongue, and buccal mucosa, along with spontaneous gingival bleeding and hemorrhagic petechiae on the palate. Laboratory tests revealed thrombocytopenia (5000/mm3), whereas the blood count showed normality in the red and white series. After excluding other etiological factors or associated diseases, the patient was diagnosed with severe ITP and began treatment with systemic corticosteroids in the intensive care unit, resulting in a successful increase in platelets. After a 2‐year follow‐up, the patient remains free of ITP recurrences. Conclusion: Oral manifestations may be one of the first signs of ITP. Therefore, it is essential that dentists are familiar with the condition and, when faced with unusual oral bleeding, consider the possibility of a hematological disorder such as ITP, ensuring a correct and early diagnosis. Moreover, the presence of ITP can further exacerbate complications associated with TS. Therefore, rigorous follow‐up of these patients is crucial, considering the high incidence of cardiovascular and autoimmune diseases and the reduced life expectancy of these patients. [ABSTRACT FROM AUTHOR]

Objective To explore the mechanism of the effect of itraconazole ethanolamine tablets on the CD40/CD40L axis in children with idiopathic thrombocytopenic purpura （ITP）. Methods 80 children with ITP were selected as the study subjects. They were divided into a control group （n = 40） and a study group （n = 40） using a digital random table method. The control group was treated with cyclosporine, while the study group was treated with itraconazole ethanolamine tablets. Both groups were treated continuously for 3 months. Compare the clinical efficacy of two groups of patients T lymphocyte subpopulation levels ［CD3+ CD4+ and CD4+/CD8+, as well as adverse reactions. Detect CD40 on the surface of lymphocyte membrane and platelet membrane in two groups of patients CD40L level, plasma sCD40 and sCD40L levels were detected using ELISA. Results The total effective rate of the study group （92.50%） was significantly higher than that of the control group （75.00%） （P < 0.05）. CD3+ CD4+, CD4+/CD8+, The expression levels of sCD40 in plasma were higher than before treatment, CD8+ and peripheral blood CD19+ CD40+ The expression levels of CD3+, CD40L+ cells, and plasma sCD40L were lower than before treatment; Research group CD3+ CD4+, CD4+/CD8+, The expression level of sCD40 in plasma was higher than that in the control group, CD8+, And peripheral blood CD19+ CD40+ The expression levels of CD3+ CD40L+ cells and plasma sCD40L were lower than those of the control group （P < 0.05）. The CD40L+ cells on the surface of peripheral blood platelet membranes after two treatment groups were lower than before treatment; The CD40+ on the surface of peripheral blood platelet membrane in the study group was higher than that in the control group, CD40L+ cells were lower than those in the control group （P < 0.05）. The total adverse rate of the study group （15.00%） was lower than that of the control group （22.50%）, but there was no significant difference between the two groups （P > 0.05）. Conclusion The treatment of ITP in children with eltrombopag olamine tablets has good clinical efficacy, regulates the level of T lymphocyte subsets, and is safe. [ABSTRACT FROM AUTHOR]

Immune thrombocytopenia (ITP) is a prevalent hemorrhage condition that causes notable immune-related abnormalities. Recently discovered data has shown that the intestinal flora plays a crucial role in maintaining a balanced immune system. Furthermore, an imbalance in gut flora has the potential to increase the possibility of developing ITP. Moreover, some studies reported a strong link between inflammatory bowel disease (IBD) and ITP. In this review, we described the significance of gut immunity in ITP. In addition, we explored the associations between gut flora and ITP as well as IBD and ITP. Finally, we examined the effectiveness of existing therapies that regulate gut homeostasis and their impact on the prognosis of patients with ITP. [ABSTRACT FROM AUTHOR]

Summary This retrospective study aimed to analyse the course and outcome of recurrent immune thrombocytopenia (ITP) in children and to identify factors associated with recurrence. A total of 497 newly diagnosed ITP children with platelet <30 × 109/L between January 1988 and December 2019 were included. Recurrent ITP was defined as a new event of thrombocytopenia after at least 3 months of remission without treatment. Twenty‐nine (5.8%) children experienced 48 recurrent episodes. The median time from diagnosis to recurrence was 22 months. Most recurrences occurred in children aged 1.5–10 years with a recent infection history. Compared to non‐recurrent ITP, children with recurrent ITP had delayed remission with lower platelets at 1 month and 3 months postdiagnosis. Multivariate analysis identified aged 1.5–10 years (hazard ratio [HR] 3.65, 95% confidence interval [CI]: 1.35–9.82) and delayed remission at 7–12 months (HR 4.04, 95% CI: 1.37–11.95) as predictors for recurrence. Most recurrent ITP patients had minor or mild symptoms, higher platelet counts, did not require treatment, and achieved remission within 12 months. The similar remission trajectories among the first and recurrent ITP, but different from the courses in the non‐recurrent ITP, suggest that recurrent ITP might have a unique biological basis. [ABSTRACT FROM AUTHOR]

The article discusses the successful treatment of a patient with refractory immune-mediated thrombotic thrombocytopenic purpura (iTTP) using daratumumab after multiple failed treatments, including splenectomy. Daratumumab, a humanized anti-CD38 antibody, has shown promise in treating refractory iTTP patients by rapidly increasing ADAMTS13 activity. The treatment led to a complete immunological response in most patients, with minimal adverse effects reported. The article highlights the potential of daratumumab as a promising option for multirefractory iTTP patients, although long-term efficacy and safety require further investigation. [Extracted from the article]

Introduction: Immune thrombocytopenia (ITP) secondary to durvalumab, a programmed cell death ligand 1 inhibitor, is a rare but clinically significant immune-related adverse event. Herein, we present 2 patients with cholangiocarcinoma who developed ITP immediately post-yttrium-90 radioembolization (Y90-RE) while on durvalumab-based systemic therapy. We hypothesize that given the timing, the immunotherapy and the radioembolization combination led to this event. It is not uncommon given the approval of immunotherapy and its role in locoregional therapies, that patients are treated with a combination of systemic immunotherapy and radioembolization or other forms of radiation, thus signifying the importance of potential complications. Case Presentation: Two patients, a 67-year-old female and a 60-year-old man, with biopsy-proven advanced unresectable cholangiocarcinoma, received a combination of systemic therapy with durvalumab, gemcitabine, and cisplatin and subsequently Y90-RE. Both patients developed ITP following in the immediate post-Y90-RE period. All other causes of ITP were comprehensively ruled out and treatment for ITP was initiated in the form of high-dose steroid and intravenous immunoglobulins. Durvalumab was discontinued, and only gemcitabine/cisplatin-based chemotherapy was continued thereafter. Due to recurrence, one of the patients required longer courses of steroids as well as thrombopoietin receptor agonists. Conclusion: Immunotherapy in the form of durvalumab and now pembrolizumab alongside chemotherapy is an approved first-line standard of care. Furthermore, it is not uncommon for patients to receive Y90-RE to improve patient outcomes. This report highlights the development of ITP in 2 patients who received durvalumab alongside Y90-RE. Awareness of this as a potential immune-mediated event is important to allow for close monitoring of platelet counts and for early intervention/management when this occurs. [ABSTRACT FROM AUTHOR]

Summary Imbalanced nicotinamide adenine dinucleotide (NAD+) homeostasis has been reported in multiple autoimmune diseases and supplementation with NAD+ precursors has consistently demonstrated positive therapeutic benefits for these conditions. Immune thrombocytopenia (ITP) is an acquired autoimmune disease, in which the decreased number and impaired function of regulatory T cells (Tregs) contribute to the main pathogenesis. Here we found NAD+ level was decreased in the plasma and CD4+ T cells of ITP patients. Supplementation with NAD+ precursor nicotinamide (NAM), but not nicotinamide mononucleotide (NMN), increased Treg frequency and ameliorated thrombocytopenia in an ITP murine model. Moreover, whilst both NAM and NMN restored cytosolic NAD+ level in the CD4+ T cells from ITP patients, only NAM promoted Treg differentiation. Mechanistically, Sirtuin1 (Sirt1), a major consumer of NAD+, was highly expressed in the CD4+ T cells of ITP patients, potentially contributing to the low level of NAD+. NAM, which could act as Sirt1 inhibitor, promoted Foxp3 acetylation and stability in induced Tregs derived from naïve CD4+ T cells of ITP patients. These findings suggest that NAM holds promise as a novel therapeutic strategy for restoring immune balance in ITP. [ABSTRACT FROM AUTHOR]

Summary In primary immune thrombocytopenia (ITP), predictors of disease evolution and treatment response are needed. Data based on the site of platelet destruction are scarce. We performed a retrospective single‐centre study of adult patients with primary ITP undergoing at least one Indium‐111 platelet scintigraphy (IPS) between 2009 and 2018. Thirty‐three patients had isolated hepatic platelet destruction (H‐group), and 97 isolated splenic destruction (S‐group). Median age at diagnosis (p < 0.001), proportion of associated cardiovascular (p < 0.001), organ‐specific autoimmune diseases (p = 0.02), dependence on steroids (p = 0.003) and failure to rituximab (p = 0.01) were higher and relapse more frequent (p = 0.03) in H‐group compared to non‐splenectomized patients in S‐group. Splenectomy was only performed in patients from S‐group (as patients with hepatic sequestration are not splenectomized in our centre): 79% were in relapse‐free remission at the end of a median 3.4‐year post‐IPS follow‐up, 16% relapsed. In multivariate analyses, only a history of organ‐specific autoimmune or inflammatory disease was significantly associated with hepatic sequestration (OR = 4.3, 95% CI = 1.2–15, p = 0.02). Patients with isolated hepatic sequestration were older, had more cardiovascular events and organ‐specific autoimmune diseases, greater dependence on steroids, more relapses and a decreased response rate to rituximab suggesting an increased refractoriness to immunomodulatory therapies. Patients with isolated splenic sequestration responded well to splenectomy. [ABSTRACT FROM AUTHOR]

Immune checkpoint inhibitors (ICIs) have become an important treatment modality for various malignancies. Due to excessive inflammatory and immune responses, immune-related adverse events (irAEs), such as rash, pruritis, pneumonitis, hepatitis, hypothyroidism, hyperthyroidism and fatigue, can occur. Acquired immune thrombocytopenia is a rare irAE that can lead to severe low platelet counts and hemorrhage. A retrospective observational analysis was conducted on data from the United States Food and Drug Administration Adverse Event Reporting System (FAERS). We searched for all reports recorded in the FAERS covering the period from 2011 Q1 to 2023 Q4 for target agents. Signal analysis was performed using the reporting odds ratio (ROR), proportional reporting ratio (PRR), Bayesian confidence propagation neural network (BCPNN) and multi-item gamma Poisson shrinker (MGPS) algorithm. Nonparametric tests were used to compare the time to onset of thrombocytopenia-associated fractures between different regimens. There were 404 reports of immune thrombocytopenia in the FAERS database. Immune thrombocytopenia was associated with all ICIs except tremelimumab, and signals were detected by all 4 methods. The median time to the onset of immune thrombocytopenia caused by PD-1, PD-L1 and CTLA-4 inhibitors was 47 days (range: 21-139.2), 21 days (range: 13–131) and 9 days (range: 7–27), respectively. The Weibull shape parameter test revealed that pembrolizumab-, durvalumab-, and ipilimumab-induced thrombocytopenia had a random failure-type profile, and nivolumab- and atezolizumab-induced thrombocytopenia were characterized by an early failure-type profile. There was a significant reporting signal of ICI-induced thrombocytopenia associated with most ICIs. Immune thrombocytopenia has a greater incidence in males, elderly individuals and Asian populations, and PD-1 inhibitors were the most common cause. Clinicians should be aware of the signs of potential serious adverse events. [ABSTRACT FROM AUTHOR]

Objectives: The study aimed to identify factors influencing the severity of primary immune thrombocytopenia (ITP) during pregnancy, develop a predictive model for treatment response, and report maternal and neonatal outcomes associated with severe ITP. Design: A retrospective analysis was conducted on 155 pregnancies with severe ITP between January 2018 and April 2023 at a tertiary critical maternity referral center in Shanghai, China. Participants/Materials: The study included 155 pregnancies diagnosed with severe ITP, divided into groups based on the lowest platelet count (<30 × 109/L vs. 30–50 × 109/L) and first-line treatment response (non-response vs. response). Setting: The study was conducted at Renji Hospital, Shanghai Jiao Tong University School of Medicine, a tertiary critical maternity rescue referral center. Methods: Clinical characteristics and outcomes were compared between groups. A multivariable logistic regression model was used to identify factors associated with the severity of ITP. A prediction model for treatment response was established using LASSO-logistic regression and internally validated. Results: ITP severity was found to be correlated with low maximum amplitude of thromboelastography (OR 5.43, 95% CI: 1.48–16.00, p = 0.002), bleeding events (OR 4.91, 95% CI: 1.62–14.86, p = 0.005), and low reticulocytes (OR 2.40 × 10−7, 95% CI: 1.06 × 10−13 to 0.55, p = 0.04). Of the 118 patients who received first-line therapy, 52 (44%) responded. The dataset was randomly split into a training (N = 99) and test (N = 23) set with a ratio of 8:2. A predictive nomogram was created and internally validated showing good discrimination. The model yielded an area under receiver operating characteristic curve of 0.78 (0.69–0.87) and 0.85 (0.67–1.00) in the training and validation cohort, respectively. Earlier delivery and high rate of neonatal intensive care unit admission occurred with severe ITP and treatment failure. Limitations: The study was limited by a relatively small sample size and the retrospective observational design, which imposed limitations on the assessment of treatment efficacy. Conclusions: We identified clinical predictors of ITP severity and treatment resistance during pregnancy. A nomogram predicting first-line response was validated. These findings can facilitate clinical decision-making and counseling regarding this challenging pregnancy complication. [ABSTRACT FROM AUTHOR]

Background: Vancomycin-induced bleeding has been reported, attributed to the mechanism of immune thrombocytopenia. A rare case of vancomycin-induced gastrointestinal hemorrhage in a young patient with no underlying disease, receiving intravenous vancomycin for methicillin-resistant Staphylococcus aureus (MRSA) infection, is presented. This occurrence occurred without thrombocytopenia. Relevant cases reported in the literature were also reviewed. Case presentation: A 34-year-old male patient presented with maxillofacial multiple spaces infection accompanying left temporal abscess, bilateral lung abscesses. Culture results from both blood and secretion indicated that the infection was caused by MRSA. The patient received standard-dose vancomycin (1 g q12h intravenously guttae) for treatment. On the 5th day of therapy, he presented with bright red blood in his stool; however, vancomycin treatment was continued. By the 9th day, a decrease in hemoglobin level to 76 g/L and a platelet (PLT) count of 424 × 109/L raised concerns about gastrointestinal hemorrhage. The hemoglobin level decreased to 62 g/L on day 12. Due to the high tissue concentration of linezolid, administration of linezolid at a dose of 600 mg q12h intravenously guttae commenced on the 13th day as an alternative to vancomycin(D13-D17). Subsequently, on the 17th day, there was an improvement in hemoglobin level to 78 g/L. However, despite treatment with linezolid, the patient's fever showed no significant improvement, prompting a switch back to vancomycin at a dosage of 1 g q12h intravenously guttae(D18-D22). On the 21st day, there was a recurrence of gastrointestinal hemorrhage, accompanied by a hemoglobin level of 42 g/L and a PLT count of 224 × 109/L. Gastroscopy revealed the presence of a gastroduodenal ulcer. The patient had no prior history of hemorrhoids, gastrointestinal ulcers, liver cirrhosis, or purpura. Prior to admission, he had not been administered non-steroidal anti-inflammatory drugs (NSAIDs) or steroids. During hospitalization, the only medications given were vancomycin, ambroxol and lidocaine. Additional tests ruled out immunological disorders as the cause of gastrointestinal ulcers, and a positive vancomycin rechallenge test indicated an association between vancomycin and bleeding. After discontinuation of vancomycin, no further bleeding occurred. This case highlights a rare occurrence of vancomycin-induced bleeding without thrombocytopenia, classified as "Certain" according to the World Health Organization-Uppsala Monitoring Centre (WHO-UMC) scale for standardized case causality assessment. Conclusion: This case represents the first documented instance of vancomycin-induced bleeding without thrombocytopenia, as confirmed by a positive rechallenge test. This discovery will aid in the early detection of this rare adverse reaction in future cases. [ABSTRACT FROM AUTHOR]

Summary Due to the limited real‐world research on the application of avatrombopag (AVA) for immune thrombocytopenia (ITP) in China, we evaluated the effectiveness and safety of AVA in clinical practice. We included 121 adult ITP patients treated with AVA across three medical centres. Based on the reasons for choosing AVA, these patients were divided into eltrombopag (ELT)/hetrombopag (HET) intolerance group (IG), and ELT/HET unresponsive group (UG). Compared with UG, more patients in IG had a history of liver disease and received fewer treatments before AVA. Amongst all patients, 83% had platelet response (≥30 × 109/L) after AVA and 62% achieved complete response (≥100 × 109/L, CR). Sixty‐two percent in IG and 56% in UG were able to discontinue more than one concomitant ITP medication. A total of 17 patients underwent multiple switches of thrombopoietin receptor agonists (TPO‐RAs), resulting in an 88% platelet response rate. Sixty‐three patients discontinued AVA, 27% were due to unaffordability. AVA was well tolerated in most patients. In the ITP population, AVA proved effective and safe, particularly in patients intolerant or unresponsive to ELT/HET. Patients benefited from TPO‐RAs switches, particularly those undergoing multiple switches. However, many patients struggled with the long‐term financial burden of AVA. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Summary: Recent evidence suggests that immune thrombocytopenia (ITP), a common bleeding disorder, is linked to an imbalance in macrophage polarization and impaired bone marrow mesenchymal stem cells (BMSCs). However, the relationship between macrophage polarization imbalance and functional defects in BMSCs, as well as the involvement of associated molecules in BMSCs' defects, is not well understood. This study aimed to investigate the regulatory effects of high mobility group protein 1 (HMGB1) on the physiological functions of BMSCs, specifically in relation to macrophage polarization imbalance. Patients with ITP showed dysregulation in monocyte/macrophage polarization and impaired BMSCs function. HMGB1 was found to have a negative impact on the ability of BMSCs to regulate the imbalance in macrophage polarization, especially when inflammatory factors are present. The MyD88‐dependent pathway downstream of BMSCs was found to be significantly enhanced with HMGB1 treatment. Furthermore, treatment with toll‐like receptor 4 (TLR4) inhibitors successfully restored the regulatory capacity of BMSCs in ameliorating macrophage polarization imbalance and effectively inhibited the activation of the MyD88‐dependent pathway. Meanwhile, infusion of si‐TLR4‐BMSCs reversed HMGB1‐induced platelet dysfunction and reduced over‐polarization to M1‐like macrophages in the ITP mouse model. Consequently, targeting the HMGB1‐TLR4 pathway could be a potential approach to restore the immunoregulatory function of BMSCs. [ABSTRACT FROM AUTHOR]

Summary: The association of autoimmune cytopenia (AIC) and inflammatory bowel disease (IBD) has been reported in small series, but the incidence of and risk factors for IBD in children with AIC are not known. One thousand six hundred nine children with chronic immune thrombocytopenic purpura, autoimmune haemolytic anaemia or Evans syndrome from the prospective OBS'CEREVANCE cohort are included in this study. Overall, 15 children were diagnosed with IBD, including 14 who developed IBD after AIC diagnosis (median delay: 21 months). The only risk factor for IBD development is age at AIC over 10 years. Out of 10 children genetically tested, germline variants associated with autoimmune disorders were identified in three (CTLA4: two, DOCK11: one). In children and adolescents monitored for AIC or past history of AIC, especially children over 10 years, gastro‐intestinal (GI) symptoms (recurrent abdominal pains, GI bleeding, chronic diarrhoea, weight loss) should suggest IBD and deserve specific work‐up and genetic studies. Identification of a causal germline variant will allow targeted therapy. [ABSTRACT FROM AUTHOR]

Summary: Patient characteristics and platelet responses at romiplostim initiation according to the duration of immune thrombocytopenia (ITP) are poorly understood. Amongst romiplostim‐exposed adults with ITP lasting ≥6 months during 2009–2018 in Denmark, Sweden, and Norway, we examined characteristics at romiplostim initiation, romiplostim dosage, and durable platelet response (≥75% of measurements ≥50 × 109/L at 14–24 weeks) for subcohorts with newly diagnosed (duration <3 months), persistent (3–12 months), or chronic (>12 months) ITP initiating romiplostim. The 285 romiplostim initiators comprised 81 (28%) with newly diagnosed, 47 (16%) with persistent, and 157 (55%) with chronic ITP. More patients with newly diagnosed ITP than longer ITP duration, had low comorbidity levels, two or more prior ITP therapies, and previous bleeding requiring hospitalisation. The median romiplostim doses were similar across subcohorts. During treatment, median platelet counts were similar across subcohorts (75–76 × 109/L), and the durable platelet response was 64.6%, 52.9%, and 52.7% for newly diagnosed, persistent, and chronic ITP, respectively. After treatment cessation, the median platelet count was 138 × 109/L, 68 × 109/L, and 71 × 109/L, respectively. In conclusion, newly diagnosed patients, compared with romiplostim initiators with longer disease duration, had more severe ITP, higher frequency of durable platelet response, and higher median platelet count after cessation. [ABSTRACT FROM AUTHOR]

Anti‐platelet factor 4 immunothrombotic syndromes comprise a group of disorders that include heparin‐induced thrombocytopenia and vaccine‐induced immune thrombocytopenia and thrombosis. These are highly prothrombotic, immunological disorders characterised by specific clinical and pathological criteria which include thrombocytopenia and thrombosis. While they are predominantly triggered by heparin and the adenoviral vector vaccines, respectively, other provoking factors have been described, as well as spontaneous forms. The unexplained co‐occurrence of thrombocytopenia with thrombosis should raise suspicion and prompt testing. This nutshell review discusses the pathophysiology, presenting features and diagnostic criteria for these conditions. [ABSTRACT FROM AUTHOR]

Summary: The Kids ITP Tools (KIT) is a health‐related quality of life (HRQoL) questionnaire that evaluates quality of life in children with immune thrombocytopenia (ITP). There are three formats: Child Self‐Report, Parent Proxy‐Report and Parent Impact‐Report. This study aimed to develop a domain structure by grouping‐related questions from the questionnaire into domains that independently reflect various aspects of HRQoL. The study was conducted in two phases. Phase 1 involved an online survey distributed to experts to identify conceptual domains for the KIT. Phase 2 utilized a statistical approach to analyse responses from patients with ITP and their families. A revised KIT 2.0 was ultimately developed to aid in treatment decision‐making and monitoring of ITP. [ABSTRACT FROM AUTHOR]

The article in the British Journal of Haematology discusses the treatment of refractory severe idiopathic immune thrombocytopenia (ITP) with daratumumab, an anti-CD38 antibody. The study reports on a case series of seven patients who received daratumumab treatment, with four patients achieving sustained complete remission. The findings suggest that daratumumab may be a valid treatment option for refractory ITP patients, leading to durable responses in some cases. Additional data from prospective clinical trials are needed to further evaluate the efficacy of daratumumab in treating ITP. [Extracted from the article]

Summary: Immune thrombocytopenia (ITP) refractory to multiple therapies may require a combination of drugs targeting different mechanisms and targets. In this retrospective, multicentre, international study, we report the safety and effectiveness of avatrombopag and fostamatininb in combination administered to 18 patients with multirefractory ITP. Overall, the combination response was achieved in 15 patients (83.3%), with a median time from combination start to best response of 15 days (IQR: 8–35 days). After a median follow‐up of 256 days (IQR: 142.8–319), 5 patients relapsed (26.7%), all during tapering or stopping one drug. Adverse events were described in 6 of 18 patients (33%). [ABSTRACT FROM AUTHOR]

Objective • To analyze the expression of platelet membrane glycoprotein sialylation in primary immune thrombocytopenia and provide a reference for clinical diagnosis and treatment of the disease. Methods • 100 children with primary immune thrombocytopenia diagnosed and treated in the Children’s Hospital of Yunhe District Central Hospital of Cangzhou City, Hebei Province from January 2020 to June 2022 were included in the study group. All children were treated with dexamethasone (DXMS) shock therapy; Another 20 healthy children who underwent routine physical examination at the same time were selected and included in the control group. The study measured the platelet membrane surface in plasma using flow cytometry in two groups: the comparative study group and the control group. The study measured the positive rates of α 2,3-sialic acid (α 2, 3-sa) and α 2,6-sialic acid (α 2, 6-sa) in both groups. The study also measured the positive rates of α 2,3-sialic acid (α 2, 3-sa) and α 2,6-sialic acid (α 2, 6-sa) before and after treatment in the comparative study group. At the same time, an enzyme-linked immunosorbent assay was used to determine the content of sialic acid and sialidase activity and content in the serum. The detection values of α2, 3-SA, and α2, 6-SA expression of children in the study group and the control group were compared, and the detection values of α2, 3-SA, and α2, 6-SA expression of children in the study group before and after treatment were compared. Results • There was no significant difference in the positive rate of α 2, 3-sa between the study group and the control group (t=0.852, P > .05); Study Group: The positive rate of α 2,6-sa was significantly lower than that of the control group (P < .05). In the study group, there was no significant difference in the positive rate of α 2,3-sa before and after treatment (P > .05). However, after treatment, the positive rate of α 2,6-sa was significantly higher than before (P < .05). The study found that the children in the study group had significantly higher levels of serum sialic acid content, sialidase activity, and content than those in the control group (P < .05). After treatment, the children in the study group showed a decrease in serum sialic acid content, sialidase activity, and content, which was statistically significant (P < .05) compared to before treatment. Conclusion • The sialylation of platelet membrane glycoprotein is abnormally expressed in primary immune thrombocytopenia. The sialylation of platelet membrane glycoprotein may be involved in the occurrence and development of the disease. It is of great practical significance to diagnose and evaluate the therapeutic effect of the disease by detecting the sialylation of platelet membrane glycoprotein. [ABSTRACT FROM AUTHOR]

Background: Patients with chronic immune thrombocytopenia (cITP) have troubles with their immune system. Nevertheless, the exact role of the immune checkpoint pathway in the development of cITP remains unknown. We aimedto investigate the impact of programmed death-1 (PD-1, PDCD1) SNPs (rs1386349 and rs2227982) on the susceptibility and clinical features of cITP. Methods: Thirty cITP pediatric patients and thirty sex and agematched healthy children were included as a control group. Routine laboratory investigations were done at the Clinical Pathology Department, Faculty of Medicine, Zagazig University, and detecting PDCD1 polymorphisms using a polymerase chain reaction (PCR)- restriction fragment length polymorphism (RFLP) system. Results: Regarding SNP (rs2227982), 80.0% of the cases group had genotype CC, 20.0% had genotype CT, and no one had genotype TT. 90.0% of the control group had genotype CC, 10.0% had genotype CT, and no one had genotype TT, 90.0% of the cases group had Allele C, and 10.0% had Allele T, 95.0% of the control group had Allele C, 5.0% had Allele T, according to SNP (rs1386349), 83.3% of the cases group had genotype CC, 13.3% had genotype CT, and 3.3% had genotype TT, 86.7% of the control group had genotype CC, 13.3% had genotype CT, and no one had genotype TT, 90.0% of the cases group had Allele C, and 10.0% had Allele T, 93.3% of the cases in the control group had Allele C, and 6.7% had Allele T. Conclusions The Pd1 gene polymorphisms (rs1386349 and rs2227982) do not affect susceptibility or clinical features among cITP patients. [ABSTRACT FROM AUTHOR]

Evans syndrome (ES) is rare and mostly treated on a "case‐by‐case" basis and no guidelines are available. With the aim of assessing disease awareness and current management of adult ES, a structured survey was administered to 64 clinicians from 50 Italian participating centers. Clinicians had to be involved in the management of autoimmune cytopenias and were enrolled into the ITP‐NET initiative. The survey included domains on epidemiology, diagnosis, and therapy of ES and was designed to capture current practice and suggested work‐up and management. Thirty clinicians who had followed a median of 5 patients (1–45)/15 years responded. The combination of AIHA plus ITP was more common than the ITP/AIHA with neutropenia (p <.001) and 25% of patients had an associated condition, including lymphoproliferative syndromes, autoimmune diseases, or primary immunodeficiencies. The agreement of clinicians for each diagnostic test is depicted (i.e., 100% for blood count and DAT; only 40% for anti‐platelets and anti‐neutrophils; 77% for bone marrow evaluation). Most clinicians reported that ES requires a specific approach compared to isolated autoimmune cytopenias, due to either a more complex pathogenesis and a higher risk of relapse and thrombotic and infectious complications. The heterogeneity of treatment choices among different physicians suggests the need for broader harmonization. [ABSTRACT FROM AUTHOR]