Background Rheumatoid arthritis (RA) is associated with inflammation-driven hypercoagulability and increased venous thromboembolic risk. Post hoc analyses of safety trials have raised concerns regarding a potential differential thrombotic risk with Janus kinase inhibitors (JAKi) compared with tumour necrosis factor inhibitors (TNFi). Objectives To compare viscoelastic coagulation profiles and platelet reactivity in patients with RA treated with JAKi or TNFi, and in healthy controls (HC). Methods In this single-centre observational study, patients with RA with stable JAKi or TNFi therapy (>3 months) underwent whole-blood rotational thromboelastometry (ROTEM) and impedance aggregometry (MULTIPLATE). The primary outcomes were evaluation of: (a) whole-blood thrombogenic potential and (b) platelet reactivity. Multivariable linear regression adjusted for age, body mass index, ln-transformed Simple Disease Activity Index, treatment group and ln-transformed prednisone dose. Results Sixty-one patients with RA (30 JAKi, 31 TNFi) and 34 HC were included. Compared with HC, patients with RA exhibited significantly higher maximum clot firmness (MCF) across all ROTEM assays (INTEM 63.4±4.0 vs 57.2±4.1 mm; EXTEM 66.2±4.1 vs 55.9±4.7 mm; FIBTEM 15.7±3.6 vs 12.4±3.7 mm; all p<0.001) and enhanced platelet aggregation (all p<0.001). In multivariable analyses, JAKi therapy (vs TNFi) was independently associated with higher EXTEM MCF (β=2.32, 95% CI 0.42 to 4.23; p=0.018) and FIBTEM MCF (β=1.72, 95% CI 0.07 to 3.37; p=0.041). Prednisone dose independently predicted INTEM and EXTEM MCF, while SDAI independently predicted ADP-induced aggregation (β=11.34, 95% CI 4.31 to 18.37; p=0.002). Conclusions RA is characterised by enhanced clot firmness and platelet reactivity. JAKi therapy was independently associated with higher viscoelastic clot strength compared with TNFi, while inflammatory burden and glucocorticoid exposure were key determinants of prothrombotic signatures.

PURPOSE:To study COVID-19-associated coagulopathy and the clinical outcomes across different COVID-19 pandemic waves. METHODS:We retrospectively analyzed n 344 patients hospitalized for acute COVID-19 to Padova University Hospital between March 2020-March 2023, grouped by variants: Wild-type (G1, n 155; March 2020-January 2021), Alpha (G2, n 79; February-May 2021), Delta (G3, n 50; May-December 2021), and Omicron (G4, n 60; December 2021-March 2023). We compared traditional coagulation tests, thromboelastometry and impedance aggregometry. Clinical outcomes were also considered. RESULTS:Factor VIII decreased progressively from G1 (195%, IQR 149-227) to G4 (156%, IQR 128-197; p < 0.05), as did von Willebrand factor (343%, IQR 244-407 to 235%, IQR 216-247; p < 0.05). Thromboelastometry showed a significantly and progressively: i) prolonged INTEM and EXTEM clot formation time (p < 0.05 in all comparisons); ii) reduced INTEM, EXTEM and FIBTEM maximum clot firmness (p < 0.05 in all comparisons). Platelet aggregation significantly decreased from G1 to G4 (p < 0.05 in all comparisons). VTE occurred in 18.1% of G1 and 19.0% of G2 patients vs. 6.0% and 6.7% in G3 and G4, respectively (p < 0.05 in all comparisons). The 28-day mortality was 15.5% in G1 and 15.2% in G2 vs. 4.0% and 1.7% in G3 and G4, respectively (p < 0.05 in all comparisons). CONCLUSIONS:We observed a significant and progressive decrease in hypercoagulability across the four COVID-19 variants. A parallel decline in VTE incidence and 28-day mortality was also observed. Larger studies are needed to ascertain the pathophysiological mechanisms underlying the changes in coagulative profiles and their clinical implications.

Lipoprotein(a) [Lp(a)] is a well-established genetic risk factor for atherosclerotic cardiovascular disease, though its role as a prothrombotic risk factor remains only partially understood. We report the case of a 64-year-old woman with markedly elevated Lp(a) levels (925 nmol/L, reference range < 105 nmol/L) and a history of recurrent major cardiovascular events, despite optimal lipid-lowering and antiplatelet therapies. We confirmed a hypercoagulable profile via comprehensive functional assessment of hemostasis: enhanced thrombin generation, reduced sensitivity to thrombomodulin, platelet hyperreactivity, and increased clot firmness at thromboelastometry — with residual platelet activity despite antiplatelet treatment. This case suggests a possible association between markedly elevated plasma Lp(a) levels and a hypercoagulable profile, which may enhance atherogenesis. Global coagulation and platelet function assays may help identify high-risk patients with elevated Lp(a) levels who may benefit from tailored antithrombotic strategies.

BACKGROUND AND AIMS:Bleeding risk in cirrhotic patients undergoing invasive procedures is traditionally assessed using conventional coagulation tests, which poorly reflect the rebalanced haemostatic state of cirrhosis and often lead to unnecessary transfusions. Viscoelastic testing (VET) provides a global assessment of coagulation and may enable more rational transfusion strategies. We performed a systematic review and meta-analysis of randomised controlled trials (RCTs) to evaluate the efficacy and safety of VET-guided transfusion strategies in this setting. METHODS:We systematically searched PubMed, Embase and Scopus from inception to 10 April 2026. RCTs comparing VET-guided versus standard-of-care transfusion strategies in cirrhotic patients undergoing invasive procedures were included. Primary outcome was procedure-related bleeding; secondary outcomes included transfusion requirements. Risk ratios (RRs) with 95% confidence intervals (CIs) were pooled using the Mantel-Haenszel method. RESULTS:Six RCTs including 296 patients were analysed. Procedure-related bleeding was rare and did not differ between groups (RR 0.74, 95% CI 0.24-2.31; I2 = 0%). In contrast, VET-guided strategies significantly reduced transfusion requirements, including any blood product transfusion (RR 0.33, 95% CI 0.26-0.44; I2 = 56%), platelet transfusion (RR 0.20, 95% CI 0.13-0.32; I2 = 40%), any fresh frozen plasma (FFP) exposure (RR 0.40, 95% CI 0.28-0.57; I2 = 63%) and FFP-only transfusion (RR 0.22, 95% CI 0.10-0.46; I2 = 81%). CONCLUSIONS:VET-guided transfusion strategies significantly reduce blood product utilisation without increasing bleeding risk in cirrhotic patients undergoing invasive procedures. These findings support a shift towards a physiology-based approach to haemostasis, with potential benefits for patient safety and resource optimisation. TRIAL REGISTRATION:ClinicalTrials.gov identifier: CRD420261382437.

BACKGROUND AND AIMS:Cirrhosis is characterized by progressive immune dysregulation, endothelial dysfunction, and haemostatic imbalance. Circulating extracellular vesicles (EVs) have emerged as potential biomarkers reflecting these pathophysiological processes. We aimed to determine whether EVs mirror disease severity and predict liver-related outcomes in cirrhosis. METHODS:In this prospective single-centre study, patients with compensated, stable decompensated, or acutely decompensated cirrhosis were enrolled. EVs were isolated from platelet-poor plasma and quantified by flow cytometry to characterize platelet-, endothelial-, immune-, and CK18+ EVs, EVs expressing markers associated with endothelial anticoagulant pathways and tissue remodelling. Primary endpoints were first hepatic decompensation in compensated cirrhosis and a composite of further decompensation, acute-on-chronic liver failure, or liver-related mortality in acutely decompensated cirrhosis. Associations were analysed using Fine-Grey competing-risk models. RESULTS:We included 228 patients, including 75 compensated, 44 stable decompensated, and 109 acutely decompensated. Median follow-up was 418 days. EV profiling showed progressive increases in total, platelet-derived, endothelial-, immune-derived, and tissue remodelling-associated EVs across Child-Pugh stages, suggestive of increasing thrombo-inflammatory and endothelial perturbation. First hepatic decompensation occurred in 7 patients with compensated cirrhosis and was associated with higher MELD and Child-Pugh scores, alcohol-related aetiology, and lower platelet count. In univariate competing-risk analyses, higher levels of several EV subpopulations were associated with first decompensation, but these associations disappeared after adjustment for MELD. Among patients with decompensated cirrhosis, 65 developed further decompensation, ACLF, or liver-related death; higher CRP levels were associated with these events, whereas no EV subpopulation was associated with the composite outcome. CONCLUSIONS:Circulating EVs reflect cirrhosis severity and are suggestive of progressive thrombo-inflammatory, endothelial, and tissue-remodelling changes. However, EVs were not independently associated with clinical outcomes.

BACKGROUND:Evidence comparing direct oral anticoagulants (DOACs) with vitamin K antagonists (VKAs) remains uncertain, particularly in patients whose index event is venous thromboembolism (VTE). OBJECTIVE:To compare the effectiveness and safety of DOACs versus VKAs after an index VTE in APS and, as an exploratory objective, to identify APS features associated with recurrent thrombosis (rTEs). METHODS:We conducted a retrospective cohort study of 84 consecutive adults fulfilling 2023 ACR/EULAR APS classification criteria and followed between 2010 and 2025 after an index VTE. Patients received VKAs (n = 54) or DOACs (n = 30). The primary efficacy outcome was rTEs during treatment; bleeding was the primary safety outcome. Time-to-event and propensity-score methods were used to address differences between treatment groups. Phenotype analyses were considered exploratory. RESULTS:Over 686.2 patient-years, 25 rTEs occurred. Recurrence was more frequent with DOACs than with VKAs (46.7% vs. 20.4%; p = 0.012), with incidence rates of 12.2 and 1.9 events per 100 patient-years, respectively. In multivariable Cox analysis, DOACs exposure was associated with earlier recurrence (HR 4.1, 95% CI 1.7-10.3; p = 0.002), and the association remained in propensity-score analyses. Microvascular involvement was more frequent among patients with rTEs (40.0% vs. 13.6%; p = 0.007). Bleeding rates were low and did not differ significantly between groups. CONCLUSIONS:In this single-centre cohort restricted to APS patients with an index VTE, DOACs exposure was associated with more frequent and earlier recurrent thrombosis than VKAs therapy, without an evident bleeding advantage. Microvascular involvement may mark a higher-risk phenotype, but this exploratory finding requires confirmation in larger prospective cohorts.

Paroxysmal nocturnal hemoglobinuria (PNH) is a rare hematological disorder characterized by intravascular hemolysis, bone marrow failure, and increased thrombotic risk. Previous studies using plasma thrombin generation tests in PNH patients yielded conflicting results. Given the central role of cellular blood components in PNH, we hypothesized that whole blood thrombin generation (WB-TG) may provide a more comprehensive assessment of patients' coagulation profile. We report the case of a 25-year-old woman with PNH and admitted to Padova University Hospital for hemolytic crisis following an influenza A virus infection. WB-TG performed upon admission revealed a hypercoagulable profile vs. healthy controls. The patient was immediately initiated on corticosteroids with good response (i.e., hemoglobin values) and subsequent resolution of hemolysis within ten days. Antithrombotic prophylaxis was administered and no thrombotic events occurred. WB-TG may be a valuable tool in the clinical management of PNH, particularly for the early identification of hypercoagulability and tailoring anticoagulant regimens.

The long-term prognostic impact of frailty in older adults recovering from COVID-19 remains underexplored. The Multidimensional Prognostic Index (MPI) has shown utility in predicting short-term outcomes, but its role over extended follow-up requires further investigation. The objective of this study is to evaluate the ability of an MPI-based model to predict 3.5-year mortality in older adults hospitalized for COVID-19. This single-center cohort study with prospective follow-up included 183 patients aged ≥ 65 years hospitalized with confirmed SARS-CoV-2 infection. MPI was calculated at admission and dichotomized into low (classes 1–2) and high (class 3). Multivariable Cox regression was used to estimate the hazard of mortality over a 3.5-year follow-up. Discriminative performance was assessed using time-dependent ROC analysis, with AUC values compared between the multivariable model and MPI alone. During follow-up, 81/183 patients (44.3

Anti-platelet factor 4 (PF4) antibody-mediated disorders are a heterogeneous group of diseases characterized by the presence of highly pathogenic immunoglobulins G directed against PF4 and/or PF4/heparin complexes. These antibodies are able to activate platelets, neutrophils, and monocytes, thus resulting in thrombocytopenia and a hypercoagulable state. Five different forms of anti-PF4 antibody-mediated disorders have been identified: (1) classic heparin-induced thrombocytopenia (HIT) mediated by heparin and certain polyanionic drugs; (2) autoimmune HIT characterized by the presence of anti-PFA/polyanion antibodies that can strongly activate platelets even in the absence of heparin; (3) spontaneous HIT characterized by thrombocytopenia and thrombosis without proximate exposure to heparin, with two subtypes: (a) post-total knee arthroplasty and cardiac surgery using cardiopulmonary bypass or extracorporeal membrane oxygenation and (b) postinfections; (4) vaccine-induced immune thrombotic thrombocytopenia (VITT) characterized by thrombocytopenia, arterial and venous thrombosis, or secondary hemorrhage after receiving adenoviral vector vaccines for coronavirus disease 2019; (5) VITT-like disorders triggered by adenoviral infections. Although extremely rare and largely unknown, there has been growing interest in the VITT syndrome in recent years due to its clinical relevance. Timely detection of these antibodies is crucial for the diagnosis and treatment of anti-PF4 antibody-mediated disorders, via anti-PF4 antibody immunoassays using several antibody capture systems (e.g., enzyme-linked immunosorbent assay-based, particle gel, turbidimetry) and functional assays (e.g., serotonin release assay or heparin-induced platelet activation). We aimed to present the latest on laboratory findings, clinical characteristics, and therapeutic approaches for anti-PF4 antibody-mediated disorders.

Vitamin D plays a key role in regulating the immune system and vaccine response, and hypovitaminosis D is a known risk factor for mortality. However, its potential influence on mortality in SARS-CoV-2 vaccinated older adults remains underexplored. This study aims to examine survival differences between unvaccinated and vaccinated older adults with varying vitamin D levels, and to assess the impact of vitamin D on mortality. We recruited patients aged 65 and over from the Geriatrics Unit of Azienda Ospedale - Università Padova. Clinical, pharmacological data, including vaccination status and vitamin D levels, were collected at admission, alongside mortality data 12 months post-hospitalization. Participants were divided into three groups: unvaccinated, vaccinated with vitamin D levels of 25–50 nmol/L, and vaccinated with levels > 50 nmol/L. A total of 126 participants were included (56

AIMS AND METHODS:Hazardous alcohol use poses an increasing public health issue worldwide and it manifests as excessive consumption (acute or chronic), which may lead to addiction. The risk of alcohol-related pathologies correlates with the patterns of intake and increases with the amount of alcohol consumed. While the effects of alcohol consumption on ischemic stroke and ischemic heart disease are well documented, the impact on venous thromboembolism is less clear. Conflicting studies have reported that alcohol may be a risk factor for, or have a protective role against venous thromboembolism. Our narrative review aimed to assess the risk of unusual-site venous thrombosis in individuals with hazardous alcohol use, as it may stem from alcohol-related organ damage (e.g. liver cirrhosis, pancreatitis) as well as provide some suggestions for physicians. RESULTS:There appears to be a correlation between hazardous alcohol use and unusual-site thrombosis, though the underlying mechanisms are largely still unknown. CONCLUSION:In subjects with hazardous alcohol use complicated by alcohol-related organ damage, physicians should be vigilant for potential thrombotic symptoms, and be prepared to diagnose and promptly initiate appropriate anticoagulation therapy.

Post-thrombotic syndrome (PTS) is the most frequent and disabling complication of deep vein thrombosis (DVT). Several studies have evaluated whether direct oral anticoagulants (DOACs) or vitamin K antagonists (VKAs) may reduce the PTS risk over time. Data on patients with inherited thrombophilias (IT) remains scarce. To assess the long-term incidence and severity of PTS in a population of IT patients with proximal DVT of the lower extremity treated with DOACs vs. VKAs. Cases were consecutive IT patients prospectively diagnosed with a first DVT episode at Padova University Hospital, Italy between January 2014 and December 2021, and treated with DOACs. Controls were consecutive IT patients diagnosed with DVT between January 2004 and December 2019, and treated with VKAs. In both groups, the onset and grade of PTS — diagnosed using the Villalta score — was evaluated at 3, 6, 12, 24 and 36 months after DVT diagnosis. We diagnosed PTS in 71 (23.0 Post-thrombotic syndrome (PTS) is a chronic complication of DVT that occurs in 20–50

IntroductionFactor XI (FXI) is associated with thrombosis in patients without liver disease, but it alterations and prognostic value in cirrhosis are uncertain.Patients and methodsWe studied a prospective cohort of cirrhosis patients determining FXI and its association with portal vein thrombosis (PVT), bleeding, and hepatic decompensation/ACLF during 1-year follow-up. Odds ratios (OR) and 95 % CIs were calculated using logistic regression.ResultsWe included 183 patients (Child-Pugh [CP] A/B/C 57/59/57). FXI was reduced in cirrhosis, decreasing with CP stage (78 % [66–94] vs. 58 % [44–78] vs. 41 % [30–52] in CP A, B, and C, respectively; p < 0.001). FXI was correlated with MELD score (rho: -0.6, p < 0.001), INR (rho: -0.6, p < 0.001), and platelet count (rho: 0.4, p < 0.001). Sixteen patients (8.7 %) experienced PVT, which only predictor was baseline platelet count (OR: 0.94; CI95 %: 0.91–0.97, p < 0.001). Bleeding occurred in 7 patients (3.8 %). Cirrhosis severity, platelet count, fibrinogen, and FXI (60% vs. 78 %; p = 0.2) were comparable between bleeding and non-bleeding individuals. Finally, no association was found between FXI and hepatic decompensation/ACLF, which were predicted by lower albumin and platelet count, respectively.ConclusionFXI seems not to be responsible for thrombosis and cirrhosis progression. The lack of association between low FXI and bleeding events, however, indirectly opens to future studies evaluating FXI inhibitors in cirrhosis.

The incidence of venous thromboembolism (VTE) in the pediatric population has increased more than 10-fold in the last 20 years, as a consequence of the advancement of resuscitation and surgical techniques and the global increase in life expectancy of children suffering from chronic pathologies. Monitoring anticoagulant therapy to achieve outcomes within the target range in childhood VTE, parenteral administration of medications, and frequent blood tests in children are often cumbersome. Availability of safe and effective oral agents with pediatric data to support use would be of clear benefit. A physiologically based pharmacokinetic model was developed to estimate the appropriate dosing schedule for rivaroxaban in children. This incorporated growth/maturation and variability in anthropometrics (e.g., body height, weight, and body mass index), anatomy (e.g., organ weight), physiology (e.g., blood flow rates), metabolism and excretion. Rivaroxaban use in pediatric population underwent a complete investigational program, consisting mainly of one phase I pharmacokinetics/pharmacodynamics trial, three phase II trials, one phase III trial. The phase III trial enrolled 500 patients from birth to <18 years and documented the efficacy and safety of rivaroxaban regimens at dose equivalent to the adult 20 mg dose for the prevention of fatal or symptomatic nonfatal recurrent VTE and major bleeding versus heparin or vitamin K antagonists. Results were similar to those in rivaroxaban studies in adults. The efficacy and safety of rivaroxaban in children reported in the EINSTEIN JUNIOR trial provide further support to previous trials in adults (EINSTEIN Program), which demonstrate a favorable profile for the use of rivaroxaban for the management of VTE in challenging patient populations. Other clinical evidence contributing to the use of rivaroxaban among different risk groups in pediatric VTE population confirms the consistency with principal trial. Our review aims to describe the rationale for using rivaroxaban oral suspension in clinical practice and to summarize its multiple indications in each vascular bed (e.g., cerebral venous thrombosis, symptomatic or asymptomatic central venous catheter-associated thrombosis), etiology, and patients setting.

Cardiac amyloidosis is a group of diseases characterized by the deposition of amyloid fibers in cardiac tissue. Two forms are mainly reported: light chain (AL) and transthyretin (ATTR) amyloidosis. Among the complications of transthyretin amyloidosis there are thrombotic events and, to a lesser extent, hemorrhagic events. The latter are likely caused by perivascular amyloid deposition resulting in capillary fragility, in addition to INR lability during anticoagulant therapy. The onset of thrombotic events may be caused by the high prevalence of atrial fibrillation (AF), mechanical cardiac dysfunction and atrial myopathy observed in patients with transthyretin amyloidosis. It remains unclear why thromboembolic events occur even in patients with sinus rhythm or adequate anticoagulation, though a hypercoagulable state or underlying inflammation may be involved. We report a case of cryptogenic ischemic stroke in an 86-year-old woman with transthyretin amyloidosis and sinus rhythm. Traditional coagulation tests, whole blood rotational thromboelastometry and impedance aggregometry did not show a hypercoagulable state. The thrombin generation assay did not reveal a prothrombotic state. However, the study of extracellular vesicles highlighted underlying immune-mediated endothelial damage likely responsible for the thrombotic diathesis. It could be hypothesized that inflammation plays a role in the hypercoagulability of patients with transthyretin amyloidosis. Larger prospective studies are needed to validate our hypothesis.