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

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

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

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

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

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

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

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

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

The long-term outcome of primary immune thrombocytopenia (ITP) is unpredictable. Chronic ITP is common in adults, requiring second-line treatments with increased morbidity and mortality. Our study aimed to identify predictive factors of chronicity at the time of diagnosis in primary adult ITP.

This retrospective multicenter study included adult patients newly diagnosed with primary ITP. Patients with a normal platelet count and no ongoing medication twelve months after disease onset were categorized in the complete remission ITP group, otherwise in the chronic ITP group.

219 patients were included, 110 in the complete remission ITP group and 109 in the chronic ITP group. In multivariate analysis, predictive factors of progression to chronicity included the absence of an infectious event preceding ITP onset (p = 0.048), the absence of bleeding manifestations (p = 0.002) and a platelet count >10 x 109/L at disease onset (p = 0.02). A poor response to initial corticosteroid treatment was also associated with chronicity, including corticosteroid dependence (p<0.001) and corticosteroid resistance (p = 0.001).

In this retrospective French cohort, predictors of chronicity in newly diagnosed primary adult ITP included the absence of preceding infectious event, platelet >10 x 109/L and absence of bleeding manifestations at onset.

To investigate the severe haematological involvement in children with SLE and assess its clinical associations, treatments, outcome and damage accrual.

The medical charts of children with SLE in whom haematological involvement was observed were reviewed. Severe haematological indices were defined as autoimmune haemolytic anaemia with a haemoglobin concentration <8 g/dl, thrombocyte count <30 000/µL and neutrophil count <500/µL.

Among the 224 patients included, 102 (45.5%) displayed severe indices, predominantly at the initial involvement, and most frequently as severe anaemia in 54 (24.1%) and severe thrombocytopenia in 45 (20.1%). Disease activity did not differ according to the presence of severe disease indices. In addition, the presence of severe indices at initial involvement did not affect the damage accrual. However, a higher rate of damage (51.1% vs 29.9%, P = 0.002) and steroid-induced damage (28.9% vs 8.2%, P < 0.001) was evident in patients with flares of the haematological system. Regression analysis revealed that rituximab treatment during the initial episode (OR: 4.5, P = 0.006) and the presence of anticardiolipin antibodies (OR: 2.3, P = 0.014) significantly increases the odds for haematological system flare. However, severe indices at initial involvement did not increase the odds of a haematological flare.

Severe haematological indices at onset are common but not related with disease outcomes. Prevention of flares is important to improve outcomes, and a more rigorous maintenance strategy would benefit most to children who display haematological indices refractory to conventional immunosuppressants and those with anti-cardiolipin antibodies.

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

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

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

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

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.

The main treatment goal for immune thrombocytopenia (ITP) is bleeding risk reduction, particularly during procedures. While adjusting platelet thresholds with ITP treatments is recommended, platelet transfusions are commonly used despite controversial benefits. We evaluated the effectiveness of platelet transfusion in reducing post-procedure bleeding risk and identified predictive indicators of bleeding. A nationally representative database was used to develop a model predicting post-procedure bleeding risk in patients with ITP. Machine learning analyses, including random forest feature importance and Shapley additive explanations (SHAP) values, assessed 34 risk factors, including the platelet transfusion amount. The random forest model had an area under the receiver-operating characteristic curve of 93.6%. Key variables influencing bleeding risk included platelet transfusion amount, high-risk procedure, anticoagulant use, anemia, age, ITP treatment, and newly diagnosed ITP, all positively correlated with bleeding risk. Conversely, no antiplatelet or anticoagulant use and moderate- or low-risk procedures were negatively associated with bleeding risk. SHAP plots showed that platelet transfusion amount correlated with high-risk procedures, and bleeding risk increased with age in high-risk procedures. Bleeding risk in patients with ITP is primarily determined by procedural risk and patient condition, rather than platelet transfusion. Minimizing unnecessary platelet transfusions and addressing bleeding risk factors pre-procedure is crucial.

Intravenous immunoglobulin (IVIg) is the gold standard treatment for severe cases of immune thrombocytopenia (ITP). However, its cost, limited duration of efficacy and market supply tension have led French guidelines to reserve IVIg for ITP patients with formal contra-indications to corticosteroids, with French bleeding score ('Khellaf score') > 8, and corticosteroid-resistant patients either with Khellaf score ≤ 8 or in preparation for an invasive procedure or during pregnancy. We studied the prescribing practices of IVIg for ITP in real-life conditions and assessed their compliance with French guidelines. A monocentric retrospective study was conducted between 2016 and 2020 among 114 patients hospitalized in our unit, for a total of 208 IVIg treatments. In 37% of cases, the Khellaf score was >8, validating IVIg prescription according to French guidelines. In the remaining cases, reasons noted for use of IVIg included corticosteroid resistance (33.7%), preparation for an invasive procedure (8.5%), context of pregnancy (6.6%) and contra-indication to corticosteroids (3.3%). After analysis, IVIg prescription was considered valid according to current French guidelines in 84.4% of cases. Non-compliant IVIg prescription was more frequent in younger patients (p = 0.027). Concomitant anti-coagulation was also noted as an argument for IVIg prescription outside of the current French guidelines.

Thrombocytopenia is a common hematologic finding in children and adolescents. Immune thrombocytopenia (ITP) is the most common cause of this finding, but the differential diagnosis includes a growing list of genetic disorders. We aimed to report differences in phenotypes of patients with ITP, inherited platelet disorder (IPD)/primary immunodeficiency disorder (PID), and other causes, with a focus on differentiating ITP from inherited thrombocytopenia.

This retrospective, population-based observational cohort from 2006 to 2020 involved 506 Finnish children under 16 years of age presenting with isolated thrombocytopenia.

Of the 506 participants, 79.7% had ITP, 6.7% had IPD/PID, and 13.6% had other causes of thrombocytopenia. A platelet count of ≤12 × 109/L best distinguished between ITP and other reasons with a sensitivity of 60% and a specificity of 80%. Among patients with the lowest platelet count of less than 10 × 109/L, 95.9% had ITP, 3.3% had IPD/PID, and 0.8% had other causes. Severe bleeding events were reported in 20 patients (4.0%), but there were no cases of intracranial or fatal bleeding due to thrombocytopenia. Up to 50% of patients with a high suspicion of inherited thrombocytopenia remained without a specific diagnosis despite genetic testing.

ITP remains the most common cause of thrombocytopenia. A platelet count of ≤12 × 109/L often leads to an ITP diagnosis. Genetic disorders are rare but should be suspected in patients with persisting thrombocytopenia, especially with platelet counts constantly above 12 × 109/L, a positive family history, or atypical clinical features.

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.

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.

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.

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.

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.

As a versatile element for maintaining homeostasis, the chemokine system has been reported to be implicated in the pathogenesis of immune thrombocytopenia (ITP). However, research pertaining to chemokine receptors and related ligands in adult ITP is still limited. The states of several typical chemokine receptors and cognate ligands in the circulation were comparatively assessed through various methodologies. Multiple variable analyses of correlation matrixes were conducted to characterize the correlation signatures of various chemokine receptors or candidate ligands with platelet counts. Our data illustrated a significant decrease in relative CXCR3 expression and elevated plasma levels of CXCL4, 9-11, 13, and CCL3 chemokines in ITP patients with varied platelet counts. Flow cytometry assays revealed eminently diminished CXCR3 levels on T and B lymphocytes and increased CXCR5 on cytotoxic T cell (Tc) subsets in ITP patients with certain platelet counts. Meanwhile, circulating CX3CR1 levels were markedly higher on T cells with a concomitant increase in plasma CX3CL1 level in ITP patients, highlighting the importance of aberrant alterations of the CX3CR1-CX3CL1 axis in ITP pathogenesis. Spearman's correlation analyses revealed a strong positive association of peripheral CXCL4 mRNA level, and negative correlations of plasma CXCL4 concentration and certain chemokine receptors with platelet counts, which might serve as a potential biomarker of platelet destruction in ITP development. Overall, these results indicate that the differential expression patterns and distinct activation states of peripheral chemokine network, and the subsequent expansion of circulating CXCR5+ Tc cells and CX3CR1+ T cells, may be a hallmark during ITP progression, which ultimately contributes to thrombocytopenia in ITP patients.

Management of immune thrombocytopenia (ITP) beyond initial glucocorticoid therapy is challenging. In this retrospective single-centre cohort study, we compared all ITP patients relapsed or non-responsive to glucocorticoid therapy treated with either continuous TPO-RAs (n = 35) or rituximab induction (n = 20) between 2015 and 2022. While both groups showed high initial complete response rates (CR, 68.6 vs. 80.0%, ns), the overall rate of progression to the next therapy was higher after time-limited rituximab (75.0 vs. 42.9%), resulting in a lower relapse-free survival (median 16.6 vs. 25.8 months, log-rank; p < 0.05). We conclude that both treatments show similar initial efficacy and their ideal duration of therapy warrants further investigation.

Despite the predisposition to bleeding, patients with immune thrombocytopenia (ITP) may also have an increased risk of arterial and venous thrombosis, which can contribute to significant morbidity. The risk of thrombosis increases with age and the presence of cardiovascular risk factors. This narrative review explores the multifactorial nature of thrombosis in ITP, focusing on new pathological mechanisms, emerging evidence on the association between established treatments and thrombotic risk, the role of novel treatment approaches, and the challenges in assessing the balance between bleeding and thrombosis in ITP. The review also explores the challenges in managing acute thrombotic events in ITP, since the platelet count does not always reliably predict either the risk of bleeding or thrombosis and antithrombotic strategies lack specific guidelines for ITP. Notably, second-line therapeutic options, such as splenectomy and thrombopoietin receptor agonists (TPO-RAs), exhibit an increased risk of thrombosis especially in older individuals or those with multiple thrombotic risk factors or previous thrombosis, emphasizing the importance of careful risk assessment before treatment selection. In this context, it is important to consider second-line therapies such as rituximab and other immunosuppressive agents, dapsone and fostamatinib, which are not associated with increased thrombotic risk. In particular, fostamatinib, an oral spleen tyrosine kinase inhibitor, has promisingly low thrombotic risk. During the current era of the emergence of several novel ITP therapies that do not pose additional risks for thrombosis, it is critical to outline evidence-based strategies for the prevention and treatment of thrombosis in ITP patients.

There is limited information on the natural course of chronic ITP in children. We aimed to evaluate the clinical and demographic characteristics of children with chronic ITP in the era before the availability of eltrombopag.

A total of 86 children with chronic ITP between 1978-2014 were included. Demographic findings, laboratory results, clinical signs, bleeding scores, response time and time of complete remission were recorded.

The male/female ratio was 1.09, and median follow-up time was 3 years (range: 1.5-17 years). The median age at diagnosis of chronic ITP was 7 years (range: 2-17), and the median initial platelet count was 10 × 109/L (range: 1-66 × 109/L). Petechiae/ecchymoses were the most common clinical sign (86%) and followed by mucosal bleeding (39.5%). Severe bleeding was seen in 5% of the patients. None of them had intracranial hemorrhage. Twenty patients underwent splenectomy, and the rate of complete remission was 70%. Spontaneous complete remission was seen in 29% of the patients, and the median time to spontaneous complete remission was 3 years.

Our study showed that almost one-third of patients with chronic ITP experienced spontaneous complete remission in an average of 3 years, and splenectomy provided satisfactory results in severe cases. This study demonstrates the natural history of chronic ITP in childhood before the era of eltrombopag.

We aimed to identify the clinical characteristics and risk factors for chronic immune thrombocytopenia (ITP) in patients with systemic lupus erythematosus (SLE).

We retrospectively reviewed patients diagnosed with SLE-associated ITP between January 2000 and December 2021. Patient characteristics were analyzed according to the progression of chronic thrombocytopenia. No response was defined as a platelet count <30 × 109/L or less than double the baseline count after treatment. Factors associated with chronic ITP were evaluated by logistic regression analysis.

Among the 121 patients with SLE-associated ITP, 27 progressed to chronic ITP lasting more than 1 year after initial diagnosis. The median initial platelet count was significantly lower in patients with chronic thrombocytopenia than in those without the disease (16 vs. 51 × 109/L). Patients who did not achieve a response within 1 month of treatment exhibited a high probability of progressing to chronic ITP (55.6 vs. 22.3%, p < 0.001). Multivariable analysis revealed that severe thrombocytopenia at baseline (<20 × 109/L) (adjusted odds ratio [aOR] = 13.628, 95% confidence interval [CI] = 3.976-46.791) and no response within 1 month (aOR = 9.171, 95% CI = 2.776-30.298) were significantly associated with the risk of progression to chronic ITP in patients with SLE. Approximately one-quarter of the patients with SLE-associated ITP progressed to chronic ITP.

Severe thrombocytopenia and failure to achieve a response within 1 month were risk factors for the development of chronic ITP in those patients.

Immune thrombocytopenia (ITP) is an autoimmune disease characterized by an isolated decrease in platelet count and an increased risk of bleeding. The pathogenesis is complex, affecting multiple components of the immune system and causing both peripheral destruction of platelets and inadequate production in the bone marrow. In this article, we review the treatment of ITP from a historical perspective, discussing first line and second line treatments, and management of refractory disease.

Immune thrombocytopenia (ITP) is an autoimmune-mediated hemorrhagic disease. Emerging evidence indicates that FOXO1 SNPs are related to the immune dysregulation of several autoimmune diseases suggesting that FOXO1 may be involved in inflammation and pathologic activities in patients with ITP. This study aimed to evaluate whether FOXO1 gene single-nucleotide polymorphisms (SNPs) are associated with susceptibility to ITP and clinical priorities of concern include bleeding severity and sensitivity of glucocorticoid treatment. This study recruited 327 newly diagnosed ITP and 220 healthy controls. Four SNPs (rs17446593, rs17446614, rs2721068, and rs2721068) of the FOXO1 gene were detected using the Sequenom MassArray system. Bleeding severity were classified into the mild and severe groups based on the bleeding scores. ITP patients were classified as sensitive and insensitive to glucocorticoid treatment according to the practice guideline for ITP (2019 version). The frequencies of the four SNPs did not show any significant differences between the ITP and healthy control groups. Patients with AA genotype at rs17446593 (p = 0.009) and GG genotype at rs17446614 (p = 0.009) suffered more severe bleeding than patients without them. Carriers of haplotype Grs17446593Ars17446614Crs2721068Trs2755213 were protective to severe bleeding (p = 0.002). The AA genotype at rs17446593 was significantly higher in ITP patients sensitive to glucocorticoid treatment than in those insensitive to glucocorticoid treatment (p = 0.03). Haplotype Grs17446593Grs17446614Trs2721068Trs2755213 increases the risk of glucocorticoid resistance (p = 0.007). Although FOXO1 gene polymorphisms were not associated with susceptibility to ITP, the AA genotype at rs17446593 and GG genotype at rs17446614 were associated with bleeding severity. Haplotype GACT have a protective effect against severe bleeding. Patients with AA genotype at rs17446593 may tend to have good responds to glucocorticoid treatment. However, the FOXO1 gene haplotype GGTT increases the risk of glucocorticoid-resistant. Trial registration: ChiCTR1900022419.

We designed anagreement study to compare the results of bleeding assessments done in tandem by ITP patients and trained research staff. We used a modified version of the ITP Bleeding Scale, which captured the patients' worst bleeding event at any of nine anatomical sites since the time of the last assessment. Interrater agreement was determined using the 2-way kappa for the assessment of severe vs. non-severe bleeds. We analyzed 108 consecutive patients with ITP from the McMaster ITP Registry who had duplicate bleeding assessments. Two-way agreement was excellent for gynecological (k = 0.86, 95% CI 0.71-1.02), gastrointestinal (k = 1), genitourinary (k = 1), pulmonary (k = 1) and intracranial (k = 1) bleeds; good for skin (k = 0.68, 95% CI, 0.54-0.82), oral (k = 0.76, 95% CI, 0.53-0.98) and ocular (k = 0.66, 95% CI, 0.04-1-28) bleeds; and moderate for epistaxis (k = 0.58, 95% CI, 0.21-0.95). Bleeding self-assessments by ITP patients were similar to trained research staff, but disagreements in severity grades were more frequent with skin bleeds, oral bleeds and epistaxis. Bleeding self-assessments could simplify bleeding assessments in clinical trials.

Immune thrombocytopenia (ITP) is an acquired immune-mediated bleeding disorder characterized by isolated thrombocytopenia. Its estimated yearly incidence in the pediatric population is 1.9-6.4/100,000. ITP in children is usually a self-limiting and benign disorder. The clinical management of children with ITP often remains controversial, as robust randomized trials on the management of this disorder are lacking. Treatments vary widely in clinical practice and existing guidelines from hematology societies on clinical management offer indications based largely on expert opinion rather than strong evidence.

The Coagulative Disorder Working Group of the Italian Association of Pediatric Hematology and Oncology (AIEOP) developed this document to collect shared expert opinions on the management of newly diagnosed ITP, updating previous guidelines and providing recommendations to pediatricians. Each statement has been given a score expressing the strength of evidence, appropriateness and agreement among participants.

Clear-cut definitions of the clinical phases of the disease and clinical response are stated. Recommendations are given regarding the classification of bleeding symptoms, evaluation of bleeding risk, diagnosis, and prognostic factors. Specific recommendations for treatment include indications for first-line (intravenous immunoglobulins, steroids) and second-line (combined therapy, thrombopoietin receptor agonists, immunosuppressive drugs, rituximab) therapeutic agents, as well as hemorrhagic emergency and supportive treatment, including emergency splenectomy. The optimal follow-up schedule, the relation between ITP and vaccines and health-related quality-of-life issues are also discussed.

The panel achieved broad consensus on issues related to how to treat children with newly diagnosed ITP, providing a comprehensive review of all relevant clinical aspects.

To describe and compare real-world treatment patterns and clinical outcomes among individuals with immune thrombocytopenia (ITP) receiving second-line therapies (rituximab, romiplostim, or eltrombopag).

A retrospective cohort study was conducted using a large administrative claims database (January 2013-May 2020) among continuously enrolled patients ≥18 years prescribed second-line ITP therapies. The index date was the date of the first claim of the study medications. Treatment patterns and outcomes were measured during the 12-month follow-up period. Inverse probability of treatment weighting (IPTW) was used to balance covariates across treatment groups. Multivariable logistic regression was used to compare treatment patterns and bleeding risk outcomes.

A total of 695 patients were included (rituximab, N = 285; romiplostim, N = 212; eltrombopag, N = 198). After IPTW, all baseline covariates were balanced. Compared to eltrombopag, patients in the rituximab cohort were 57% more likely to receive other ITP therapies (systematic corticosteroids or third-line therapies) during the follow-up period (odds ratio [OR] = 1.571, p = .030). There was no significant difference in the odds of receiving a different second-line therapy or experiencing a bleeding-related episode among three groups (p > .050). Patients in the romiplostim cohort were 69% more likely to receive rescue therapy compared to those in the rituximab cohort (OR = 1.688, p = .025).

Patients with ITP receiving rituximab were more likely to need other ITP therapies but did not experience higher risk of bleeding compared to those receiving eltrombopag or romiplostim. Benefits, risks, cost-effectiveness, and patient preference should all be considered in optimizing second-line therapy for ITP.

Although bleeding is one of the main symptoms of primary immune thrombocytopenia (ITP), risk factors for bleeding have yet to be fully established. Low platelet count (PC; <20-30 × 109 /L) is generally indicative of increased risk of bleeding. However, PC and bleeding events cannot be fully correlated; many other patient- and disease-related factors are thought to contribute to increased bleeding risk. Furthermore, even though ITP patients have thrombocytopenia and are at increased risk of bleeding, ITP also carries higher risk of thrombotic events. Factors like older age and certain ITP treatments are associated with increased thrombotic risk. Women's health in ITP requires particular attention concerning haemorrhagic and thrombotic complications. Management of bleeding/thrombotic risk, and eventually antithrombotic therapies in ITP patients, should be based on individual risk profiles, using a tailored, patient-centric approach. Currently, evidence-based recommendations and validated tools are lacking to support decision-making and help clinicians weigh risk of bleeding against thrombosis. Moreover, evidence is lacking about optimal PC for achieving haemostasis in invasive procedures settings. Further research is needed to fully define risk factors for each event, enabling development of comprehensive risk stratification approaches. This review discusses risk-based and individualised management of bleeding and thrombosis risk in adults with primary ITP.

Intravenous immunoglobulin (IVIg) is a first-line treatment for children with newly diagnosed immune thrombocytopenia (ITP). Higher doses of IVIg are associated with a more insupportable financial burden to pediatric patients' families and may produce more adverse reactions. Whether low-dose IVIg (LD-IVIg) can replace high-dose IVIg (HD-IVIg) has yet to be established. We conducted a comprehensive literature search from the establishment of the database to May 1, 2023, and eventually included 22 RCTs and 3 cohort studies compared different dosages of IVIg. A total of 1989 patients were included, with 991 patients in the LD-IVIg group and 998 patients in the HD-IVIg group. Our results showed no significant differences between the two groups in the effective rate (LD-IVIg: 91% vs. HD-IVIg: 93%; RR: 0.99; 95%CI: 0.96-1.02) and the durable remission rate (LD-IVIg: 65% vs. HD-IVIg: 67%; RR: 0.97; 95%CI: 0.89-1.07). Similar results were also found in the time of platelet counts (PC) starting to rise (MD: 0.01, 95%CI: -0.06-0.09), rising to normal (MD: 0.16, 95%CI: -0.03-0.35), and achieving hemostasis (MD: 0.11, 95%CI: -0.02-0.23) between the two groups. Subgroup analysis showed the effective rate of 0.6 g/kg was equal to 1 g/kg subgroup (91%) but higher than 0.8 g/kg subgroup (82%), and a combination with glucocorticoid may contribute to effect enhancement (combined with glucocorticoid: 91% vs. IVIg alone: 86%) whether combined with dexamethasone (92%) or methylprednisolone (91%). Besides, the incidence rate of adverse reactions in the LD-IVIg group (3%) was significantly lower than the HD-IVIg group (6%) (RR: 0.61; 95%CI: 0.38-0.98). So low-dose IVIg (≤ 1 g/kg) is effective, safe, and economical, which can replace high-dose IVIg (2 g/kg) as an initial treatment. This systematic review was registered in PROSPERO (CRD42022384604).

Objective: To review the pharmacology, pharmacokinetics, clinical efficacy, safety, dosing and administration, and place in therapy of avatrombopag for the treatment of immune thrombocytopenia and chronic liver disease-associated thrombocytopenia. Summary: Avatrombopag is an orally administered thrombopoietin receptor agonist approved for the treatment of immune thrombocytopenia and is the first oral thrombopoietin receptor agonist approved for the treatment of perioperative thrombocytopenia associated with chronic liver disease in adults. The efficacy and safety of avatrombopag has been demonstrated in a multicenter, randomized, double blind, placebo-controlled phase III study in the setting of immune thrombocytopenia and in 2 identically designed, multicenter, randomized, double blind, placebo-controlled phase III trials in the setting of thrombocytopenia associated with chronic liver disease. The most common adverse events reported in the clinical trials were headache, fatigue, and gastrointestinal toxicities. The incidence of bleeding events was comparable between the avatrombopag and placebo treatment groups in each study. Avatrombopag has not been shown to be associated with hepatoxicity and does not require food restriction like the other oral thrombopoietin receptor agonist for immune thrombocytopenia, eltrombopag. Also, unlike eltrombopag for immune thrombocytopenia, it can be dosed less frequently than once daily. Conclusion: Avatrombopag offers another safe and effective oral option for the treatment of immune thrombocytopenia without food restrictions and an alternative, transfusion-sparing option for thrombocytopenia associated with chronic liver disease patients undergoing surgery.

Autoimmune disorders place a substantial burden on the healthcare system all over the world affecting almost 3% to 8% of the population. Immune thrombocytopenic purpura (ITP), also known as idiopathic thrombocytopenic purpura, is a blood disorder in which the body immune system destroys platelets, leading to low platelet counts in the blood (peripheral blood platelet count < 150 × 109/L). Although the pathophysiology of ITP is not fully understood, it is believed to result from a complex interplay between hereditary and environmental variables. Certain factors, such as a low platelet count, history of bleeding, and certain comorbidities can increase the risk of severe bleeding in patients with ITP. Corticosteroids, intravenous immunoglobulin (IVIG), immunosuppressants, rituximab, and thrombopoietin receptor agonists (TPO-RAs) are some of the advanced treatments for ITP. Although these therapies may be successful, they also carry the risk of negative effects. Recently, significant advancements have been made in the understanding and treatment of ITP. There is still much to learn about the disease, and new, more effective treatments are needed. This comprehensive review offers a comprehensive assessment of recent advancements in ITP management, with a focus on active research projects, novel therapeutic targets, new treatment modalities, and areas of uncertainty and unmet needs. According to research, it is crucial to develop individualized treatment plans for ITP patients based on their age, platelet count, risk of bleeding, and comorbidities. The article also looks at how future developments in gene editing, bispecific antibody therapies, and cellular therapy may completely change the treatment of ITP.

Thrombopoietin receptor agonists (TPO-RAs) have been widely used to treat thrombocytopenia, however, a scientometric profile of TPO-RAs research is lacking. Methods: This study uses VOSviewer, CiteSpace, and R software to provide an overview of current research, highlight study hotspots, and predict future research directions of TPO-RAs. Results: One thousand seven hundred and nineteen relevant studies from 1993 to 2022 with 43962 citations were identified from the Web of Science Core Collection. Over three decades, the USA has been leading TPO-RAs publications. Industries and academic institutions have been actively involved in TPO-RAs research, with funding provided by pharmaceutical companies and public funding bodies. The most productive and cited journals are British Journal of Hematology and Blood, respectively. When author keywords were categorised into three clusters, i.e., cluster 1 (immune thrombocytopenic purpura (ITP)), cluster 2 (avatrombopag, lusutrombopag, and thrombocytopenia), and cluster 3 (TPO-RAs for ITP and off-label drug use), ITP was found to be the current research hotspot, while oral TPO-RAs and licensed or unlicensed drug indications of thrombocytopenic diseases require further investigation. Conclusion: This study has generated the knowledge map of TPO-RAs, which provides a dynamic roadmap for future research in this field.

The presentation of immune thrombocytopenia is dependent on the degree of thrombocytopenia, with no to mild bleeding symptoms, primarily mucocutaneous bleeding. Severe bleeding in other organ systems is a rare complication. Spontaneous hemarthrosis is rare in patients without hemophilia. We report a child presenting with oral and cutaneous petechial lesions and left knee hemarthrosis without trauma. Laboratory findings showed severe thrombocytopenia consistent with immune thrombocytopenia. Serologic tests were consistent with Lyme disease. Hemarthrosis was presumed secondary to Lyme disease monoarticular joint inflammation with bleeding exacerbated by severe thrombocytopenia. Hemarthrosis resolved and platelet counts normalized following immunoglobulin infusion, steroid course, and antibiotics.

An elevated systemic immune-inflammation index (SII) is associated with higher mortality in patients with coronary artery disease and other diseases. However, the potential of SII for predicting mortality in the general population has been underexplored. Therefore, this study aimed to analyze the relationship between the SII and all-cause, cardiovascular disease, and cardiocerebrovascular disease mortality in the general population.

This study involved 26,855 participants (≥ 18 years) from the National Health and Nutrition Examination Survey 1999-2014 who were grouped according to the SII tertiles. Survival differences between the groups were analyzed using log-rank tests and Kaplan-Meier plots. Furthermore, multivariate Cox regression and restricted cubic spline analyses were used to examine the relationship between the SII and all-cause, cardiovascular, and cardio-cerebrovascular mortality.

Overall, 1947 (7.425%) participants died following an average follow-up of 87.99 ± 54.04 months. Among these, 325 (1.210%) deaths were related to cardiovascular diseases and 392 (1.459%) to cardio-cerebrovascular mortality. Kaplan-Meier analysis revealed statistically significant differences in all-cause, cardiovascular, and cerebrovascular mortality between the SII tertiles (log-rank test: all P < 0.001). Multi-adjusted models showed that participants in the highest tertile of SII had a higher risk of death from all-cause (hazard ratio [HR] = 1.48, 95% confidence interval [CI] 1.48-1.48) and cardiovascular mortality (HR = 1.60, 95% CI 1.60-1.61) compared with those in the lowest tertile. In addition, the restricted cubic spline curve indicated a nonlinear association between SII and all-cause mortality (P < 0.001), with threshold value of SII at 18.284. There was a 15% decrease in the risk of all-cause mortality for each twofold change in SII on the left flank (HR = 0.85, 95% CI 0.69-1.05) and a 42% increase (HR = 1.42, 95% CI 1.23-1.64) on the right flank of the inflection point. In addition, the risk of cardiovascular mortality increased nonlinearly by 39% per twofold change in SII (HR = 1.39, 95% CI 1.07-1.81). There was also a nonlinear increase in the risk of cardio-cerebrovascular mortality per twofold change in SII (HR = 1.29, 95% CI 1.00-1.66).

In the general population, the SII was significantly associated with all-cause, cardiovascular, and cardio-cerebrovascular mortality, regardless of the established risk factors.

While immune thrombocytopenia often presents with mild bleeding manifestations or surprising findings of thrombocytopenia on routine complete blood counts in patients without symptoms, some patients can present with new thrombocytopenia and life-threatening bleeding. Emergent assessment and treatment are needed to prevent substantial morbidity and even mortality. These patients present to the emergency room with bleeding, and hematologists are subsequently consulted. Understanding the approach to making the diagnosis and excluding other life-threatening illnesses is essential, as is rapid initiation of treatment in the bleeding patient even when the diagnosis of immune- mediated thrombocytopenia is tentative. Using a case-based format, we review how to approach and treat patients presenting with new thrombocytopenia and bleeding.

Significant decreases in platelet counts and ITP relapses have been documented in ITP patients receiving COVID-19 mRNA vaccines; however, the effect of the inactivated COVID-19 vaccine on ITP patients remains unclear. The present study aimed to investigate the impact of inactivated COVID-19 vaccines on ITP patients, with a focus on platelet dropping events, bleeding events/scores, and the requirement of a new round of treatment. A total of 118 ITP patients, with 97 chronic ITP and 21 persistent ITP, who received inactivated COVID-19 immunization were investigated retrospectively. Following vaccination (within 1 month), ITP patients reported platelet dropping (31.36 %), new bleeding events (22.88 %), increases in bleeding scores (23.73 %), and new treatment requirements (22.03 %). Among them, persistent ITP patients with disease duration of 3-12 months had higher ratios of the above adverse events (71.43 %, 57.14 %, 61.90 % and 71.43 %, respectively) than chronic ITP patients with duration > 1 year (22.68 %, 15.46 %, 15.46 % and 11.34 %, respectively); patients' disease duration was negatively correlated with platelet dropping events and new treatment requirements. Furthermore, logistic regression analysis also supported the above findings, revealing that persistent ITP patients had 9.40-9.70, 7.24-10.08, and 27.17-28.51 times incidence of having platelet dropping events, new bleeding events, and new treatment requirements after vaccination, respectively, when compared to chronic ITP patients. In conclusion, the present study demonstrates that after receiving inactivated COVID-19 vaccines, ITP patients may experience platelet dropping, which may lead to new bleeding events and the requirement of a new round of treatment for ITP recurrence. As a result, platelet level monitoring is crucial for ITP patients during the vaccination, especially those with persistent ITP.

Immune thrombocytopenic purpura (ITP) is a disorder caused by autoimmune antibodies which target glycoprotein IIb/IIIa complex or other platelet membrane antigens leading to platelet destruction. These platelets are then cleared by the spleen resulting in thrombocytopenia. Immune thrombocytopenic purpura affects about 1 to 6.4 cases in 100 000 children making it one of the most common causes of symptomatic thrombocytopenia in the pediatric population. It is rare that children or adolescents present with serious bleeding due to ITP. Common presentations include petechiae, bleeding gums, or bruising. Bleeding requiring hospitalization or transfusions is unusual and only occurs in approximately 5% of children. Even more uncommon is the presentation of severe bleeding complications requiring surgery for resolution. We present a case of a 17-year-old girl with acute ITP complicated by intraperitoneal hemorrhage and refractory thrombocytopenia due to ovarian cyst requiring oophorectomy.

Immune thrombocytopenia (ITP) is characterized by primarily autoantibody-mediated platelet destruction and impaired platelet production resulting in thrombocytopenia and an increased risk of bleeding. Other manifestations include increased risk of thrombosis and diminished quality of life. Current treatment approaches are directed toward lowering the rate of platelet destruction or stimulating platelet production to prevent bleeding. Rilzabrutinib is an oral, reversible, potent Bruton tyrosine kinase inhibitor that was specifically designed to treat immune-mediated diseases and mediates its therapeutic effect through a dual mechanism of action: (1) inhibiting B-cell activation and (2) interrupting antibody-coated cell phagocytosis by Fc gamma receptor in spleen and liver. A 24-week dose-finding phase I/II study of rilzabrutinib in patients with ITP showed a 40% platelet response (⩾2 consecutive platelet counts of ⩾50 × 109/L and increase from baseline ⩾20 × 109/L without rescue medication use) and a well-tolerated safety profile with only grade 1/2 transient adverse events across dose levels.

Assess the efficacy and safety of oral rilzabrutinib in adult and adolescent patients with persistent or chronic ITP.

Rilzabrutinib 400 mg BID is being evaluated in the ongoing LUNA 3 multicenter, double-blind, placebo-controlled phase III study.

The primary endpoint is durable platelet response, defined as achieving platelet counts of ⩾50 × 109/L for at least two-thirds of ⩾8 available weekly scheduled platelet measurements during the last 12 weeks (including ⩾2 available measurements within the last 6 weeks) of the 24-week blinded treatment period in the absence of rescue therapy.

Ethical guidelines and informed consent are followed.

The LUNA 3 trial will further investigate rilzabrutinib's safety and efficacy in adult and adolescent patients, with the primary goal of addressing a major objective in treating patients with ITP: durability of platelet response.

ClinicalTrials.gov NCT04562766: https://clinicaltrials.gov/ct2/show/NCT04562766; EU Clinical Trials Register EudraCT 2020-002063-60: https://www.clinicaltrialsregister.eu/ctr-search/search?query=2020-002063-60.