ITP is not only a bleeding disease but also a potential thrombotic disease.

This retrospective study analyzed the factors associated with the occurrence of thrombosis events in ITP patients.

The overall incidence of thrombosis was 4.66% (15/322), with the incidence of arterial events was 2.17% (7/322) and of venous thrombosis was 2.80% (9/322). Thrombosis can occur in all stages and was more common in patients with chronic ITP (66.7%). In univariate logistic analysis, age (OR = 1.037, 95%CI (1.003,1.072), p = 0.032), hypertension (OR = 3.389, 95%CI (1.184,9.699), p = 0.023), coronary artery disease (OR = 10.714, 95%CI (2.462,46.619), p = 0.002), dyslipidemia (OR = 4.325, 95%CI (1.463,12.788), p = 0.008), and treatment with TPO-RAs (OR = 5.233, 95%CI (1.448,18.918), p = 0.012) were related to increased risk thrombotic events. In multivariate logistic analysis, results showed that coronary artery disease (OR = 9.486, 95% CI (1.858, 48.42), p = 0.007), dyslipidemia (OR = 3.983, 95% CI (1.255, 12.641), p = 0.019), as well as TPO-RAs treatment (OR = 4.591, 95% CI (1.238, 17.023), p = 0.023), were independent risk factors for thrombosis in ITP patients (p < 0.05).

Thrombotic events can occur at all stages of ITP with a higher percentage in chronic ITP. Coronary artery disease, dyslipidemia and TPO-RAs treatment are independent risk factors related to thrombosis in ITP patients.

This study aimed to identify novel plasma proteins associated with first-lifetime venous thromboembolism (VTE) and molecular pathways involved in VTE pathogenesis.A case-cohort comprising incident VTE cases (n = 294) and a randomly sampled age- and sex-weighted subcohort (n = 1,066) was derived from the Trøndelag Health Study (HUNT3, n = 50,800). Blood samples were collected and stored at cohort inclusion (2006-2008), and participants were followed up to 5 years. Proteome-wide analyses was performed using the 7k SomaScan® proteomics platform, and weighted Cox-regression models adjusted for age, sex, and sample batch were conducted, with the Bonferroni method applied to account for multiple testing. Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analyses were applied on the top-ranked 200 proteins associated with VTE.Out of 7,288 human proteins, 7 proteins were significantly associated with higher VTE risk with p-value <6.9 × 10-6 (hazard ratios per 1 standard deviation increase in protein levels ranging from 1.39 to 1.86). Except for coagulation factor VIII and tumor necrosis factor soluble receptor II, these proteins were novel associations and included collagen alpha-3(VI):BPTI/Kunitz inhibitor, histo-blood group ABO system transferase, peroxidasin, human epididymis protein 4, and regulator of G protein signaling 3. KEGG analyses of the top-ranked 200 proteins revealed significant pathway enrichment of nine proteins in the complement (mainly lectin pathway) and coagulation (mainly intrinsic pathway) cascades.Our proteome-wide analysis led to discovery of five novel protein candidates associated with 5-year risk of future VTE. KEGG analyses supported an interplay between the complement and coagulation pathways in the pathogenesis of VTE.

Pyoderma gangrenosum (PG) is a neutrophilic dermatosis of unclear etiology. Numerous theories of its underlying pathogenesis have been proposed, including external triggers, neutrophilic dysfunction, complement activation, and autoimmunity, as well as a possible component of underlying genetic susceptibility. This review seeks to synthesize current understanding of the pathogenesis of PG and integrate interactions between the multitude of implicated host immune pathways to guide and inform future directions into the treatment of PG.

To evaluate the combination of novel colour Doppler US (CDUS), greyscale US (GSUS), and oscillometric indices of macroangiopathy in patients with idiopathic inflammatory myopathies (IIM). Second, to explore the associations between these imaging markers and both patient-related and disease-related characteristics, as well as traditional cardiovascular (CV) risk factors.

We conducted CDUS to evaluate arterial compliance markers, specifically the resistance (RI) and pulsatility (PI) indices, both in the common (CCA) and internal carotid arteries (ICA) of patients with IIM and healthy controls. Additionally, we performed GSUS examinations to measure carotid intima-media thickness (cIMT), identify plaques, and quantify cumulative carotid calcification surface. Oscillometric assessments determined aortic stiffness using carotid-femoral pulse wave velocity (cfPWV).

We recruited 82 IIM patients and 88 healthy controls. Patients showed significantly higher cIMT (Padj = 0.032), CCA-RI (Padj = 0.015), CCA-PI (Padj = 0.013), ICA-RI (Padj = 0.012), and ICA-PI (Padj = 0.039), compared with controls. RI and PI of CCA and ICA were higher in patients with lower lung function vital capacity, respectively (all Ps < 0.05). cfPWV correlated positively with traditional CV risk factors including age (ρ = 0.546, P < 0.001), mean arterial pressure (ρ = 0.331, P = 0.003), diabetes (P = 0.007), and hyperlipidaemia (P = 0.032), and associated negatively with lung carbon monoxide (CO) diffusion (ρ = -0.329, P = 0.031).

In one of the largest CV surrogate marker studies in IIM, patients exhibited increased carotid pulsatility, resistance, and atherosclerosis compared with controls. Lower lung function parameters predicted aortic stiffness and Doppler indices, suggesting a possible link between lung involvement and increased CV risk. Angiopathy markers may reveal significant vascular abnormalities in IIM patients, enhancing CV screening and risk classification.

Pulmonary embolism (PE) is a critical condition with significant morbidity and mortality, particularly among patients with chronic inflammatory diseases (CID) such as rheumatoid arthritis and systemic lupus erythematosus that are linked to a heightened risk of thromboembolic events.

This retrospective analysis examined 725,725 adult patients hospitalized with a primary diagnosis of PE using the National Inpatient Sample database from 2016 to 2019. Patients were stratified by CID status. The study assessed in-hospital outcomes including all-cause mortality, major adverse cardiovascular and cerebrovascular events (MACCE), major bleeding, intracranial hemorrhage, length of stay, and total hospital charges. Multivariable logistic regression models were used to examine the association between CID and in-hospital outcomes, adjusting for baseline differences.

Of the study population, 33,775 (4.6 %) had CID. Patients with CID were younger (62.07 vs 62.85 years, p < 0.001) and more likely to be female (69.9 % vs 51.0 %, p < 0.001). After adjustment, patients with CID showed an 8 % decreased mortality risk (aOR 0.92, 95 % CI: 0.86-0.98, p = 0.015) but a 15 % higher risk of major bleeding (aOR 1.15, 95 % CI: 1.08-1.23, p < 0.001). Additionally, there was a small but significant increase in the odds of MACCE for patients with CID (aOR 1.07, 95 % CI: 1.01-1.13, p = 0.014).

The findings indicate that while patients with CID experience lower in-hospital mortality rates, they are at a greater risk for major bleeding. This underscores the necessity for tailored treatment approaches that consider individual patient factors, such as age and comorbidities, to optimize outcomes in this vulnerable population.

Various studies have shown that individuals with bullous pemphigoid (BP) are more likely to develop venous thromboembolism (VTE). However, it is important to acknowledge that these studies primarily focused on individuals in Western nations, which restricts their generalization to a wider demographic. The present systematic review aims to assess the cumulative risk of VTE in individuals with BP compared to healthy individuals. PubMed, Cochrane, and Scopus databases were searched for evidence-based research papers on BP and VTE. Eligibility criteria were based on the PICOS criteria. The Newcastle-Ottawa scale assessed methodological quality. After database searches, 115 studies meeting the inclusion criteria were identified. A manual inquiry yielded an additional 11 articles. After removing duplicates (n=54), 72 publications underwent title and abstract evaluation, resulting in the exclusion of 44 manuscripts. Consequently, the remaining full-text articles were thoroughly examined. Following full-text screening, 9 publications were included. The studies were conducted in Denmark, the USA, the UK, Taiwan, and Italy. The findings enhanced the generalizability of the correlation between VTE and BP. Individuals with systemic autoimmune diseases were found to have a 1.5 to 4 times higher likelihood of developing VTE. The analysis revealed that patients with pemphigus face a twofold higher risk of VTE, especially within the first few years after diagnosis. These results may enhance the recognition of pulmonary embolism in BP patients and motivate the prevention of secondary risk markers associated with VTE. Given the morbidity, VTE risk in BP patients warrants greater attention in public healthcare.

Multiple sclerosis (MS) is a chronic autoimmune disease characterized by inflammation and neurodegeneration. Our original study analyzes the interactions between blood platelets and leukocytes in MS, focused on their potential role in modulating immune responses. We demonstrated, for the first time, a significant increase in leukocyte migration towards platelets, indicating their higher chemotactic capabilities in MS. This novel finding is supported by microscopic imaging of platelet-leukocyte hetero-aggregates (PLAs). Our study included platelet activation status and platelet-lymphocyte cross-talk analysis distinguishing lymphocytic subpopulation in patients with relapsing-remitting (RRMS) and secondary progressive MS (SPMS) compared to healthy controls (HC). Flow cytometry method revealed an elevated expression of platelet activation typical markers i.e. PAC-1 and CD62P in both phenotypes of MS, especially in RRMS, and higher GPVI level in SPMS. Detailed immunophenotyping and confocal imaging showed an increased pool of platelet-lymphocyte aggregates (PLAs-Ly), particularly involving B-cells over T-cells across both MS phenotypes. The study also explored the involvement of the CD40-CD40L pathway, discovering significant correlations between platelet CD40L expression and lymphocytic antigen CD40, especially on B-cells in SPMS. This novel finding may indicate the special significance of platelet-B-cell cross-talk in progressive disease phenotype. Our research identified potential platelet-leukocyte interaction pathways that may influence the lymphocyte-mediated immune response in MS, highlighting the unexplored formation of platelet-B cell hetero-aggregates (PLAs-LyB).

This study aimed to analyze the published data pertaining to the correlation between venous thromboembolism (VTE) and systemic sclerosis (SSc).

We conducted manual searches and explored MEDLINE, EMBASE, and Cochrane databases to review papers reporting the risk of VTE in patients with SSc. A meta-analysis was performed exploring the relative risks (RRs) of deep vein thrombosis (DVT), pulmonary embolism (PE), and VTE in these individuals.

Six trials that included 41,105 patients with SSc were eligible for inclusion. A meta-analysis of the six included studies revealed a statistically significant correlation (RR 2.372, 95% confidence interval [CI] = 1.608-3.500, p < 0.001) between the risk of VTE and SSc. Regional subgroup study revealed a strong correlation between SSc and VTE risk in Americans, Europeans, and Asians. Additionally, a significant correlation between SSc and PE risk was observed (RR 3.154, 95% CI = 1.320-7.539, p = 0.010). Finally, the meta-analysis revealed a substantial correlation (RR 5.190, 95% CI = 1.513-17.01, p = 0.009) between the risk of DVT and SSc.

This meta-analysis showed that SSc is linked to an increased risk of DVT, PE, and VTE. This finding underscores the importance of close monitoring for the emergence of these conditions in patients with SSc.

Despite the well-established association between chronic inflammatory conditions and pulmonary embolism(PE), previous investigations of the relationship between Dermatomyositis(DM) and Polymyositis(PM) with PE were scarce and have been subject to significant limitations, including small sample sizes and failure to account for potential confounders.

To investigate the correlation between DM/PM and PE, as well as assessing the impact of serologic status, myonecrosis, and inflammation markers on this relationship.

In this large, nationwide population-based study, we used the Clalit Health Services medical database and extracted all DM/PM patients who were first diagnosed between 1 January 2002 to 31 December 2018 and compared them with age and gender matched controls in a ratio of 1:5. Serological and laboratory values were obtained for each patient. Rates of PE were compared between groups using multivariate models.

The study included 1557 DM patients with 7633 controls, and 528 PM patients with 2560 controls. Compared with matched controls, the rates of PE were significantly higher in the DM/PM group, PM patients(2.8 % vs 0.5 % in controls, OR = 5.73, p < 0.001), DM patients(1.2 % vs 0.3 % in controls, OR = 3.42, p < 0.001). APLA seropositivity was significantly more prevalent in DM/PM patients compared with their matched controls, PM patients(10.8 % vs 2.7 % in controls, p < 0.001), DM patients(7.9 % vs 1.6 % in controls, p < 0.001). APLA seropositivity had a synergistic effect for PE in the DM/PM(OR = 23.18, p < 0.001).

DM and PM are associated with higher rates of PE. Furthermore, patients with DM/PM demonstrate a significantly higher prevalence APLA which act as a potentiator of thrombosis in these patients.

Dermatomyositis (DM) is an autoimmune disease characterized by chronic muscle inflammation and weakness. Patients with DM are at an increased risk of thromboembolic events (TEs). This study aimed to investigate the prevalence of TEs in DM and to identify the independent predictors.

A total of 543 patients hospitalized for DM within the past 10 years were analyzed retrospectively and compared with patients with DM with and without TEs for demographic, clinical, and laboratory characteristics. The independent predictors were analyzed using multivariate logistic regression analysis. The diagnostic performance was calculated by a receiver operating curve (ROC).

Twenty-two (4.1%) patients with DM had TEs, including 12 (54.5%) with venous thromboembolism and 10 (45.5%) with arterial thromboembolism. Multivariate logistic regression analysis demonstrated that glucocorticoid therapy (odds ratio (OR)=0.003, 95% confidence interval (CI) 0.00-0.03, P<0.001) was a protective factor for the patients with DM developing TEs, whereas increased D-Dimer (OR=1.885, 95% CI 1.21-2.95, P=0.006) was a risk factor. The combined ROC analysis of glucocorticoid therapy and D-Dimer indicated high diagnostic values in distinguishing patients with both DM and TEs from patients without TEs, with 86.4% sensitivity, 98.9% specificity, and 0.983 area under the ROC curve (95% CI 0.962-1.000, P<0.001).

Patients with DM who have never received glucocorticoid therapy and have increased D-Dimer (>1.3 mg/L fibrinogen equivalent units) should be screened for TEs.

Chronic thromboembolic pulmonary hypertension (CTEPH) is a life-threatening complication post-acute pulmonary embolism (PE). The assessment of CTEPH incidence and risk factors post-acute PE in the era of direct oral anticoagulants remains insufficient.

The COMMAND VTE Registry-2 (contemporary management and outcomes in patients with venous thromboembolism registry-2) is a multicenter registry that recruited consecutive patients with acute symptomatic venous thromboembolism from 31 centers across Japan. The primary outcome was to demonstrate the detection rate of CTEPH after acute PE in routine clinical practice. Out of the 5197 patients with venous thromboembolism included in the COMMAND VTE Registry-2, 2787 were diagnosed with acute PE. Following a median follow-up duration of 747 days, 48 cases of CTEPH were detected, and the cumulative diagnosis of CTEPH in routine clinical practice was 2.3% at 3 years. Independent risk factors for the detection of CTEPH by multivariable Cox regression analysis included women (hazard ratio [HR] 2.09 [95% CI, 1.05-4.14]), longer interval from symptom onset to diagnosis of PE (each 1 day, HR 1.04 [95% CI, 1.01-1.07]), hypoxemia at diagnosis (HR 2.52 [95% CI, 1.26-5.04]), right heart load (HR 9.28 [95% CI, 3.19-27.00]), lower D-dimer value (each 1 μg/mL, HR 0.96 [95% CI, 0.92-0.99]), and unprovoked PE (HR 2.77 [95% CI, 1.22-6.30]).

In the direct oral anticoagulant era, the cumulative diagnosis of CTEPH after acute PE was 2.3% at 3 years, and several independent risk factors for CTEPH were identified, which could be useful for screening a high-risk population after acute PE.

Thyrotoxicosis appears to be a predisposing factor for cerebral venous thrombosis (CVT), which is a rare but important cause of stroke in young adults. The presentation of CVT is highly variable, ranging from a history of headaches (in the majority of cases) to deep coma, with the latter requiring invasive neurosurgical decompression. Although the long-term outcomes of CVT are favorable, multicenter cohort studies have shown that death may occur in up to 4% of cases in the acute phase and 8-10% of cases in the long term. It has been argued that the substantial decrease in mortality in patients with CVT that has been observed during the past few decades may be the result of an increased awareness of CVT among clinicians. Given that thyrotoxicosis is a risk factor for CVT, clinicians (and endocrinologists) should be alert to the possibility of CVT in patients with thyroid disease in order to prevent it whenever possible or treat it promptly. In this review, we provide an updated overview of the characteristics of patients with thyrotoxicosis who presented with CVT, the underlying mechanisms, and a few tips for clinicians.

The simplified Pulmonary Embolism Severity Index (sPESI) score could help identify low-risk patients with pulmonary embolism for home treatment. However, the application of the sPESI score and selection for home treatment have not been fully evaluated in the direct oral anticoagulants era.

The COMMAND VTE (Contemporary Management and Outcomes in Patients With Venous Thromboembolism) Registry-2 is a multicenter registry enrolling consecutive patients with acute symptomatic venous thromboembolism. The current study population consists of 2496 patients with hemodynamically stable pulmonary embolism (2100 patients [84%] treated with direct oral anticoagulants), who were divided into 2 groups: sPESI scores of 0 and ≥1. We investigated the 30-day mortality, home treatment prevalence, and factors predisposing to home treatment using the Kaplan-Meier method and logistic regression model. Patients with an sPESI score of 0 accounted for 612 (25%) patients, and only 17% among 532 patients with out-of-hospital pulmonary embolism were treated at home. The cumulative 30-day mortality was lower in patients with an sPESI score of 0 than the score of ≥1 (0% and 4.8%, log-rank P<0.001). There was no patient with 30-day mortality with an sPESI score of 0. Independent factors for home treatment among out-of-hospital pulmonary embolism patients with an sPESI score of 0 were no transient risk factors for venous thromboembolism, no cardiac biomarker elevation, and direct oral anticoagulants use in the acute phase.

The 30-day mortality rate was notably low in an sPESI score of 0. Nevertheless, only a minority of patients with an sPESI score of 0 were treated at home between 2015 and 2020 after the introduction of direct oral anticoagulants for venous thromboembolismin Japan.

Inflammatory rheumatic diseases (IRDs), encompassing a broad spectrum of chronic disorders, typically necessitate prolonged therapeutic intervention. Nevertheless, these diseases can sometimes manifest as severe emergencies requiring prompt and extensive medical intervention. Urgent intervention is essential for effectively recognizing and managing these situations, as they have the potential to be life-threatening and can result in severe morbidity and mortality. Emergencies in IRDs can occur with different frequencies and manifestations, including nervous system issues, severe infections, thrombosis-emboli, renal crises, gastrointestinal issues, and cardiovascular events. The fact that these events can occur across different IRDs underscores the necessity for heightened awareness and readiness among healthcare professionals. The pathophysiologic mechanisms that cause rheumatic emergencies are complex and involve multiple factors. These emergencies frequently arise due to the interplay between the inflammatory characteristics of rheumatic diseases and different systemic triggers. Early detection and treatment can have a substantial impact on an individual's prognosis in cases of severe and life-threatening disorders that require prompt recognition. Rapid decision-making and urgent care are required to effectively address rheumatic emergencies, as well as the implementation of a diagnostic flowchart. This article provides an overview of the emergencies linked to IRDs, classifying and assessing them individually. This article aims to enhance healthcare professionals' knowledge and awareness of critical situations by examining current recommendations and pathophysiological information. Implementing standardized diagnostic and treatment methods, providing patient education, and conducting continuing research into the underlying mechanisms are essential for enhancing the management of these critical situations and improving patient outcomes.

There have been limited data on the changes in clinical outcomes after the introduction of direct oral anticoagulants (DOACs) for venous thromboembolism (VTE) in real clinical practice. We evaluated the changes in management strategies and long-term outcomes from the warfarin era to the DOAC era.

We compared the 2 series of multicenter COMMAND VTE (Contemporary Management and Outcomes in Patients With Venous Thromboembolism) registries in Japan enrolling consecutive patients with acute symptomatic VTE: Registry 1: 3027 patients in the warfarin era (2010-2014) and Registry 2: 5197 patients in the DOAC era (2015-2020). The prevalence of DOAC use increased more in Registry 2 than in the Registry 1 (Registry 1: 2.6% versus Registry 2: 79%, P<0.001). The cumulative 5-year incidence of recurrent VTE was significantly lower in Registry 2 than in Registry 1 (10.5% versus 9.5%, P=0.02), and the risk reduction of recurrent VTE in Registry 2 remained significant even after adjusting the confounders (hazard ratio [HR], 0.78 [95% CI, 0.65-0.93]; P=0.005). The cumulative 5-year incidence of major bleeding was not significantly different between the 2 registries (12.1% versus 13.7%, P=0.26), and the risk of major bleeding between the 2 registries was not significantly different even after adjusting the confounders (HR, 1.04 [95% CI, 0.89-1.21]; P=0.63).

Along with the shift from warfarin to DOACs, there was a lower risk of recurrent VTE in the DOAC era than in the warfarin era, whereas there was no apparent change in the risk of major bleeding, which might still be an unmet need even in the DOAC era.

Pulmonary embolism (PE) is a severe and acute cardiovascular syndrome with high mortality among patients with autoimmune inflammatory rheumatic diseases (AIIRDs). Accurate prediction and timely intervention play a pivotal role in enhancing survival rates. However, there is a notable scarcity of practical early prediction and risk assessment systems of PE in patients with AIIRD.

In the training cohort, 60 AIIRD with PE cases and 180 age-, gender-, and disease-matched AIIRD non-PE cases were identified from 7254 AIIRD cases in Tongji Hospital from 2014 to 2022. Univariable logistic regression (LR) and least absolute shrinkage and selection operator (LASSO) were used to select the clinical features for further training with machine learning (ML) methods, including random forest (RF), support vector machines (SVM), neural network (NN), logistic regression (LR), gradient boosted decision tree (GBDT), classification and regression trees (CART), and C5.0 models. The performances of these models were subsequently validated using a multicenter validation cohort.

In the training cohort, 24 and 13 clinical features were selected by univariable LR and LASSO strategies, respectively. The five ML models (RF, SVM, NN, LR, and GBDT) showed promising performances, with an area under the receiver operating characteristic (ROC) curve (AUC) of 0.962-1.000 in the training cohort and 0.969-0.999 in the validation cohort. CART and C5.0 models achieved AUCs of 0.850 and 0.932, respectively, in the training cohort. Using D-dimer as a pre-screening index, the refined C5.0 model achieved an AUC exceeding 0.948 in the training cohort and an AUC above 0.925 in the validation cohort. These results markedly outperformed the use of D-dimer levels alone.

ML-based models are proven to be precise for predicting the onset of PE in patients with AIIRD exhibiting clinical suspicion of PE.

Chictr.org.cn : ChiCTR2200059599.

Multimorbidity, i.e., two or more non-communicable diseases (NCDs), is an escalating challenge for society. Venous thromboembolism (VTE) is a common cardiovascular disease and it is unknown which multimorbidity clusters associates with VTE. Our aim was to examine the association between different common disease clusters of multimorbidity and VTE. The study is an extended (1997-2015) cross-sectional Swedish study using the National Patient Register and the Multigeneration Register. A total of 2,694,442 Swedish-born individuals were included in the study. Multimorbidity was defined by 45 NCDs. A principal component analysis (PCA) identified multimorbidity disease clusters. Odds ratios (OR) for VTE were calculated for the different multimorbidity disease clusters. There were 16% (n = 440,742) of multimorbid individuals in the study population. Forty-four of the individual 45 NCDs were associated with VTE. The PCA analysis identified nine multimorbidity disease clusters, F1-F9. Seven of these multimorbidity clusters were associated with VTE. The adjusted OR for VTE in the multimorbid patients was for the first three clusters: F1 (cardiometabolic diseases) 3.44 (95%CI 3.24-3.65), F2 (mental disorders) 2.25 (95%CI 2.14-2.37) and F3 (digestive system diseases) 4.35 (95%CI 3.63-5.22). There was an association between multimorbidity severity and OR for VTE. For instance, the occurrence of at least five diseases was in F1 and F2 associated with ORs for VTE: 8.17 (95%CI 6.32-10.55) and 6.31 (95%CI 4.34-9.17), respectively. In this nationwide study we have shown a strong association between VTE and different multimorbidity disease clusters that might be useful for VTE prediction.

Background: Axial spondyloarthropathy(AS) is a chronic inflammatory disease primarily affecting the axial skeleton, often characterized by sacroiliitis. While pulmonary embolism (PE), a potentially lethal condition, has been linked to several autoimmune diseases, limited data exist regarding PE risk among patients with AS. Methods: This retrospective cohort study utilized the Clalit Healthcare Services (CHS) database, including 5825 patients with AS and 28,356 matched controls. Follow-up began at the date of first AS diagnosis for patients and at the matched patient's diagnosis date for controls and continued until PE diagnosis, death, or study end date. Results: Prevalence of PE before AS diagnosis in patients compared to controls was 0.4% vs. 0.2% (p < 0.01). The incidence rate of PE was 11.6 per 10,000 person-years for patients with AS and 6.8 per 10,000 person-years for controls. The adjusted hazard ratio (HR) for PE in patients with AS was 1.70 (p < 0.001). Subgroup analysis demonstrated excess risk for PE in patients with AS regardless of gender and age, with variations among AS treatment categories. Discussion: Our findings highlight a significant association between AS and PE, indicating an increased risk in patients with AS independent of age and sex and suggests a subclinical level of inflammation. Preliminary results suggest a protective role of immunosuppressing drugs. Further research into the impact of treatment strategies should be conducted and could inform clinical management and reduce the life-threatening risk of PE in Patients with AS.

As an autoimmune disease, the persistent systemic inflammatory response associated with connective tissue disease (CTD) is involved in the development of venous thromboembolism (VTE). However, clinical data showed that the risk of VTE in patients differed between subtypes of CTD, suggesting that different subtypes may have independent mechanisms to promote the development of VTE, but the specific mechanism lacks sufficient research at present. The development of pulmonary fibrosis also contributes to the development of VTE, and therefore, patients with CTD-associated interstitial lung disease (CTD-ILD) may be at higher risk of VTE than patients with CTD alone or patients with ILD alone. In addition, the activation of the coagulation cascade response will drive further progression of the patient's pre-existing pulmonary fibrosis, which will continue to increase the patient's risk of VTE and adversely affect prognosis. Currently, the treatment for CTD-ILD is mainly immunosuppressive and antirheumatic therapy, such as the use of glucocorticoids and janus kinase-inhibitors (JAKis), but, paradoxically, these drugs are also involved in the formation of patients' coagulation tendency, making the clinical treatment of CTD-ILD patients with a higher risk of developing VTE challenging. In this article, we review the potential risk factors and related mechanisms for the development of VTE in CTD-ILD patients to provide a reference for clinical treatment and prevention.

Immune thrombocytopenia (ITP) is an autoimmune disease characterized by an isolated decrease in the 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 impaired central megakaryopoiesis and platelet production in the bone marrow. Here, we intend to contextualize the current knowledge on the pathophysiology, terminology, epidemiology, clinical manifestations, diagnosis, and prognosis of ITP from a historical perspective and the first references to the never-stopping garnering of knowledge about this entity. We highlight the necessity to better understand ITP in order to be able to provide ITP patients with personalized treatment options, improving disease prognosis and reducing the incidence or frequency of refractoriness.

This study aimed to establish a nomogram to predict the risk of venous thromboembolism (VTE), identifying potential risk factors, and providing theoretical basis for prevention of VTE after spinal surgery.

A retrospective analysis was conducted on 2754 patients who underwent spinal surgery. The general characteristics of the training group were initially screened using univariate logistic analysis, and the LASSO method was used for optimal prediction. Subsequently, multivariate logistic regression analysis was performed to identify independent risk factors for postoperative VTE in the training group, and a nomogram for predict risk of VTE was established. The discrimination, calibration, and clinical usefulness of the nomogram were separately evaluated using the C-index, receiver operating characteristic curve, calibration plot and clinical decision curve, and was validated using data from the validation group finally.

Multivariate logistic regression analysis identified 10 independent risk factors for VTE after spinal surgery. A nomogram was established based on these independent risk factors. The C-index for the training and validation groups indicating high accuracy and stability of the model. The area under the receiver operating characteristic curve indicating excellent discrimination ability; the calibration curves showed outstanding calibration for both the training and validation groups. Decision curve analysis showed the clinical net benefit of using the nomogram could be maximized in the probability threshold range of 0.01-1.

Patients undergoing spinal surgery with elevated D-dimer levels, prolonger surgical, and cervical surgery have higher risk of VTE. The nomogram can provide a theoretical basis for clinicians to prevent VTE.

Thrombotic events, such as venous thromboembolism (VTE) are a major health complication linked to rheumatoid arthritis (RA). We performed a meta-analysis to evaluate the risk of VTE, including deep vein thrombosis (DVT) and pulmonary embolism (PE), in adults with RA compared to the general population.

MEDLINE and EMBASE databases were searched from inception to April 2022 to identify publications meeting the following criteria: (1) prospective and retrospective original data from cohort or case-control studies; (2) pre-specified RA definition; (3) clearly defined VTE outcomes; (4) reported risk estimate and 95% confidence intervals (95% CIs); (5) at least sex- and age-matched to comparison group; and (6) English language. Of 372 studies screened, 14 were included (602,760 RA patients, 123,076 VTE events) and their quality was assessed by an adaptation of the STROBE quality scoring scale.

The pooled risk ratios of VTE, DVT and PE in patients with RA were 1.57 (95% CI 1.41-1.76), 1.58 (95% CI 1.26-1.97) and 1.57 (95% CI 1.30-1.88), respectively. The I2 value of 92%, 94% and 92% for VTE, DVT and PE analyses, suggesting considerable heterogeneity. There were no significant differences in risk estimates among the five subgroup analyses: quality score (P = 0.35, I2 = 0%); sex (P = 0.31, I2 = 1.7%); study year (P = 0.81, I2 = 0%); population source (P = 0.35, I2 = 0%); study design (P = 0.62, I2 = 0%).

Results show that patients with RA are at a higher risk of VTE, DVT and PE compared to the general population.

Thromboembolic complications, including venous thromboembolism (VTE) and arterial thromboembolism (ATE), increase mortality and morbidity, and delay treatment in patients with cancer. Therefore, an increased understanding of underlying risk profiles, the identification of risk factors and predictive biomarkers, and ultimately the development of specific cardiovascular prevention strategies in patients with cancer is needed. Medical anticancer therapies have undergone a remarkable development in recent years with the advent of targeted and immunotherapeutic treatment options, including immune checkpoint inhibitors (ICI), chimeric antigen receptor (CAR) T-cell therapies and bispecific T-cell engagers (BiTEs). These developments have important implications for the accompanied risk of thromboembolic events in patients with cancer. First, the increased use of these highly effective therapies renders a growing proportion of patients with cancer at risk of thromboembolic events for a prolonged risk period due to an increase in patient survival despite advanced cancer stages. Second, potential direct cardiovascular toxicity and prothrombotic effect of novel anticancer immunotherapies are a matter of ongoing debate, with emerging reports suggesting a relevant risk of VTE and ATE associated with ICI, and relevant dysregulations of hemostasis in the frequently observed cytokine-release syndrome associated with BiTEs and CAR T-cell therapy. The aim of the present narrative review is to summarize the implications of the emerging use of anticancer immunotherapy for thromboembolic events in patients with cancer, and to provide an overview of available data on the rates and risk factors for VTE and ATE associated with ICI, CAR T-cell therapy, and BiTEs.

Clinical management of patients with deep vein thrombosis (DVT) is centered around their risk of recurrent venous thromboembolism (VTE) and post-thrombotic syndrome (PTS). While chronic inflammatory disease (CID) has been established as a risk factor of (recurrent) VTE, research about its potential impact on PTS is lacking.

We aimed to assess the risk of PTS in patients with CID, stratifying for the use of anti-inflammatory treatment.

Consecutive patients with proximal DVT and no active cancer between 2003 and 2018 received a two-year prospective follow-up. CID included inflammatory bowel disease, rheumatic diseases, and gout. Residual venous obstruction (RVO) was assessed by compressive ultrasound after 3-6 months. PTS was diagnosed using the Villalta score after 6-24 months. Hazard ratios (HR) and odds ratios (OR) were adjusted for patient characteristics. The medical ethics committee approved this study.

In total 82 of 801 patients had CID (10.2 %). PTS more often developed in patients with CID (35.4% vs. 18.9 %, p < 0.001) than in those without CID (HR 1.72 [1.15-2.58]). The prevalence of RVO was similar in patients with and without CID (36.8% vs. 41.4 %), and RVO was strongly associated with PTS in patients with CID (OR 3.21 [1.14-9.03]). Moreover, patients with untreated CID (44 %, n = 36) more often had RVO than those with treated CID (51.6% vs. 26.7 %, p = 0.027), and accordingly had a higher risk of PTS (HR 2.18 [1.04-4.58]).

Patients with CID had an increased risk of developing PTS, especially those without anti-inflammatory treatment, possibly due to an unfavorable impact on RVO-related venous pathology.

A variety of autoimmune disorders are associated with an increased risk of thrombosis. Previous studies have suggested combined therapy of heparin and therapeutic plasma exchange (TPE) with fresh frozen plasma (FFP) as the replacement fluid is beneficial in some cases of acute flare-up of autoimmune diseases complicated by thrombotic events. Nevertheless, it remains unknown whether clinicians do more harm than good by exposing patients to a "thrombotic storm" through simultaneous administration of heparin and the clotting factors in the FFP during TPE. A variety of data are currently available on therapeutic interventions for autoimmune diseases complicated with acute thrombosis; however, there is limited evidence on the exact efficacy of each individual approach and combinations of these measures. Herein, we report a case of catastrophic antiphospholipid syndrome (CAPS) to highlight the difficulty of therapeutic decision-making when complicated interactions occur between heparin and TPE. To our knowledge, this is the first case report of a patient diagnosed with CAPS successfully treated with a novel therapeutic strategy of escalating the heparin dosage when performing TPE by monitoring the partial prothrombin time to reduce the risk of the progression of thrombosis.

Dermatitis herpetiformis (DH) is a cutaneous manifestation of coeliac disease. Increased cardiovascular morbidity has been reported in coeliac disease, but in DH only little is known about this. In this cohort study with a long-term follow-up, the risk for vascular diseases in patients with dermatitis herpetiformis (DH) and coeliac disease was assessed.

The study consisted of 368 DH and 1072 coeliac disease patients with biopsy-proven diagnosis performed between 1966 and 2000. For each DH and coeliac disease patient three matched reference individuals were obtained from the population register. Data regarding all outpatient and inpatient treatment periods between 1970 and 2015 were reviewed for diagnostic codes of vascular diseases from the Care Register for Health Care. Cox proportional hazard model was used to assess the risks for the diseases studied and the HRs were adjusted for diabetes mellitus (aHR).

The median follow-up time of DH and coeliac disease patients was 46 years. The risk for cardiovascular diseases did not differ between DH patients and their references (aHR 1.16, 95% CI 0.91-1.47), but among coeliac disease patients, the risk was increased (aHR 1.36, 95% CI 1.16-1.59). The risk for cerebrovascular diseases was found to be decreased in DH patients when compared with references (aHR 0.68, 95% CI 0.47-0.99) and increased in coeliac disease patients (aHR 1.33, 95% CI 1.07-1.66). The risk for venous thrombosis was increased in coeliac disease patients (aHR 1.62, 95% CI 1.22-2.16) but not in DH.

The risk for vascular complications appears to differ between DH and coeliac disease. In DH the risk for cerebrovascular diseases seems to be decreased, while in coeliac disease an elevated risk for cerebrovascular and cardiovascular diseases was observed. These differing vascular risk profiles between the two manifestations of the same disease merit further investigation.

Observational studies suggest that the occurrence of stroke on multiple sclerosis (MS) patients is higher compared to the general population. MS is a heterogeneous disease that involves an interplay of genetic, environmental and immune factors. The occurrence of stroke is subject to a wide range of both modifiable and non-modifiable, short- and long-term risk factors. Both MS and stroke share common risk factors. The immune mechanisms that underlie stroke are similar to neurodegenerative diseases and are attributed to neuroinflammation. The inflammation in autoimmune diseases may, therefore, predispose to an increased risk for stroke or potentiate the effect of conventional stroke risk factors. There are, however, additional determinants that contribute to a higher risk and incidence of stroke in MS. Due to the challenges that are associated with their differential diagnosis, the objective is to present an overview of the factors that may contribute to increased susceptibility or occurrence of stroke in MSpatients by performing a review of the available to date literature. As both MS and stroke can individually detrimentally affect the quality of life of afflicted patients, the identification of factors that contribute to an increased risk for stroke in MS is crucial for the prompt implementation of preventative therapeutic measures to limit the additive burden that stroke imposes.

It is estimated that 2% to 3% of the population are currently prescribed systemic or topical glucocorticoid treatment. The potent anti-inflammatory action of glucocorticoids to deliver therapeutic benefit is not in doubt. However, the side effects associated with their use, including central weight gain, hypertension, insulin resistance, type 2 diabetes (T2D), and osteoporosis, often collectively termed iatrogenic Cushing's syndrome, are associated with a significant health and economic burden. The precise cellular mechanisms underpinning the differential action of glucocorticoids to drive the desirable and undesirable effects are still not completely understood. Faced with the unmet clinical need to limit glucocorticoid-induced adverse effects alongside ensuring the preservation of anti-inflammatory actions, several strategies have been pursued. The coprescription of existing licensed drugs to treat incident adverse effects can be effective, but data examining the prevention of adverse effects are limited. Novel selective glucocorticoid receptor agonists and selective glucocorticoid receptor modulators have been designed that aim to specifically and selectively activate anti-inflammatory responses based upon their interaction with the glucocorticoid receptor. Several of these compounds are currently in clinical trials to evaluate their efficacy. More recently, strategies exploiting tissue-specific glucocorticoid metabolism through the isoforms of 11β-hydroxysteroid dehydrogenase has shown early potential, although data from clinical trials are limited. The aim of any treatment is to maximize benefit while minimizing risk, and within this review we define the adverse effect profile associated with glucocorticoid use and evaluate current and developing strategies that aim to limit side effects but preserve desirable therapeutic efficacy.

Autoimmune diseases have specific pathophysiologic mechanisms leading to an increased risk of arterial and venous thrombosis. The risk of venous thromboembolism (VTE) varies according to the type and stage of the disease, and to concomitant treatments. In this review, we revise the most common autoimmune disease such as antiphospholipid syndrome, inflammatory myositis, polymyositis and dermatomyositis, rheumatoid arthritis, sarcoidosis, Sjogren syndrome, autoimmune haemolytic anaemia, systemic lupus erythematosus, systemic sclerosis, vasculitis and inflammatory bowel disease. We also provide an overview of pathophysiology responsible for the risk of VTE in each autoimmune disorder, and report current indications to anticoagulant treatment for primary and secondary prevention of VTE.

A number of studies have suggested that multiple sclerosis (MS) can be associated with serious vascular complications, for which pulmonary thromboembolism (PTE) is a potentially lethal complication. The purpose of this study is to establish a current literature-based estimate of the incidence of venous thromboembolism (VTE), deep vein thrombosis (DVT), and PTE in patients with MS (pwMS) due to the lack of systematic reviews and meta-analyses on this topic. In this systematic review and meta-analysis, studies were assessed regarding the association between MS and the incidence of VTE. The studies were identified through a systematic search of major electronic databases spanning the period from 1950 to February 2022. A random-effects analysis was conducted to calculate the pooled effect size (ES) and 95% confidence intervals (CI) using STATA software. Nine out of 4605 studies were included in the meta-analysis, with an overall sample size of 158,546 individuals. Meta-analysis revealed that the pooled incidence of VTE was 1.8% (95% CI 1.4-2.3) among pwMS. Also, there was an incidence of 0.9% (95% CI 0.4-1.4) and 1.5% (95% CI 1-2.2) for PTE and DVT, respectively in pwMS. Analysis showed MS would be significantly associated with a twofold increased risk of VTE [risk ratios (RR) = 2.12 (95% CI 1.53-2.93)]. Although MS is not typically considered a major risk factor for VTE, the meta-analysis of cohort studies shows that MS has a relative association with an increased incidence of VTE. Future research should focus on the investigation of the effects of MS and its treatments on VTE risk, and also a full range of confounding adjustments will be needed.

There is a scarcity of national population-based studies on polymyositis (PM)/dermatomyositis (DM) readmissions in the USA. In this study, we aim to describe the rates, reasons for readmissions, and characteristics of readmissions for adults hospitalized for PM/DM in the USA.

We analyzed the 2018 Nationwide Readmissions Database (NRD). We included index hospitalizations for all adult DM/PM patients with a principal diagnosis of PM/DM using ICD-10 codes. We excluded elective and traumatic readmissions. Using a "rank" command in STATA, the most common specific principal diagnosis of readmissions was outlined. Chi-square tests were used to compare baseline characteristics between readmissions and index hospitalizations. STATA 16 was used for analysis.

A total of 1610, 1286, and 842 index hospitalizations with a principal diagnosis of PM/DM, that were discharged alive, were included in the 30-, 90-, and 180-day readmission analysis, respectively. Among these, 193 (12%), 276 (21.5%), and 240 (28.5%) were readmitted within 30, 90, and 180 days, respectively. PM and sepsis were the most common reasons for reasons across the 3 timeframes. 30-day readmissions were responsible for an aggregate of 4.1 million US dollars in total hospital cost and 1518 hospital days in 2018. Compared to index hospitalizations, 30-day readmissions have higher Charlson Comorbidity Index scores, severe-extreme loss of function, obesity, and deep venous thrombosis.

About a third of PM/DM hospitalized patients are readmitted within 180 days. Readmissions constitute a significant economic burden to the health care system. PM and sepsis are the main reasons for readmissions. Key points • About a third of polymyositis (PM)/dermatomyositis (DM) hospitalized patients are readmitted within 180 days • PM and sepsis are the main reasons for readmissions. • Readmissions of PM/DM Patients constitute a significant economic burden to the health care system. • Compared to index hospitalizations, 30-day readmissions have higher Charlson comorbidity index scores, severe-extreme loss of function, obesity, and deep venous thrombosis.

An increased risk of atherosclerotic and thrombotic complications characterizes connective tissue diseases. Endothelial dysfunction is the basis for the initiation and progression of atherosclerosis and thrombosis. We present systemic lupus erythematosus (SLE) as a model rheumatic disease with endothelial dysfunction and discuss its mechanisms, factors that influence the early onset and rapid progression of atherosclerosis, and the increased risk of thromboembolic events. We focus on established methods to improve endothelium function, including statins, antiplatelet, and antithrombotic therapy. Hypercoagulable and hypofibrinolitic states and a hyperinflammatory response characterize severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. Several pathogenic mechanisms are typical for an acute phase of Covid-19 post-Covid syndrome and connective tissue diseases: endothelial dysfunction, elevated antiphospholipid antibody titer, activation of the complement system, and formation of extracellular neutrophil traps (NET). The current review discusses the mechanisms underlying SLE and the COVID-19 in the context of endothelial function, atherosclerosis, and thrombosis (Graphical abstract). Key Points • The pathophysiology of systemic lupus erythematosus (SLE) and Covid-19 shows some similarities, such as endothelial cell activation and dysfunction, the activation of complementary systems, the presence of antiphospholipid antibodies, and the formation of extracellular neutrophil traps. • Autoimmunity in both diseases creates the basis for hyperinflammatory, hypercoagulable, and hypofibrinolitic states and their thromboembolic complications. • This paper presents our perspective on the mechanisms behind the cardiovascular manifestations of SLE and COVID-19, with a particular emphasis on endothelial dysfunction. Covid-19 and systemic lupus erythematosus-potential similarities in pathophysiology. Figures of the panel illustrate the clinical manifestations of endothelial dysfunction, atherosclerosis, and thromboembolism, including coronary artery disease ([A] coronary angiography with left anterior descending artery stenosis and [B] scintigraphy with reduced perfusion in the myocardial apical segments), stroke ([C] carotid angiography, left carotid artery occlusion) and pulmonary embolism ([D]computed tomography with thrombus in the right pulmonary artery).

Background Bullous pemphigoid (BP) and pemphigus vulgaris (PV) share similar pathophysiology with venous thromboembolism (VTE) involving platelet activation, immune dysregulation, and systemic inflammation. Nevertheless, their associations have not been well established. Methods and Results To examine the risk of incident VTE among patients with BP or PV, we performed a nationwide cohort study using Taiwan's National Health Insurance Research Database and enrolled 12 162 adults with BP or PV and 12 162 controls. A Cox regression model considering stabilized inverse probability weighting was used to calculate the hazard ratios (HRs) for incident VTE associated with BP or PV. To consolidate the findings, a meta-analysis that incorporated results from the present cohort study with previous literature was also conducted. Compared with controls, patients with BP or PV had an increased risk for incident VTE (HR, 1.87 [95% CI, 1.55-2.26]; P<0.001). The incidence of VTE was 6.47 and 2.20 per 1000 person-years in the BP and PV cohorts, respectively. The risk for incident VTE significantly increased among patients with BP (HR, 1.85 [95% CI, 1.52-2.24]; P<0.001) and PV (HR, 1.99 [95% CI, 1.02-3.91]; P=0.04). In the meta-analysis of 8 studies including ours, BP and PV were associated with an increased risk for incident VTE (pooled relative risk, 2.17 [95% CI, 1.82-2.62]; P<0.001). Conclusions BP and PV are associated with an increased risk for VTE. Preventive approaches and cardiovascular evaluation should be considered particularly for patients with BP or PV with concomitant risk factors such as hospitalization or immobilization.