Pulmonary vascular obstruction index (PVOI), assessed using the Qanadli index on computed tomography pulmonary angiography (CTPA) at pulmonary embolism (PE) diagnostic, has been associated with recurrence after unprovoked PE, but its complexity limits routine use. We aimed to evaluate simplified semiquantitative (Sq) measures of initial PVOI for predicting recurrent PE after anticoagulation discontinuation.This post hoc analysis, based on the double-blind, randomized PADIS-PE trial where patients with a first unprovoked PE initially treated during 6 months were allocated to receive either an additional 18-month warfarin or placebo, was restricted on the 180 patients who had PE diagnosed by CTPA. Initial PVOI was assessed using four methods: Qanadli score, modified Qanadli score, anatomical-based SqPVOI1, and lobe-based SqPVOI2. Accuracy and associations with recurrent PE were evaluated using area under the curve (AUC) analysis and Cox regression models.Among the 180 included patients (mean age 66.2 ± 16.5 years; 45.2% female), recurrent PE occurred in 42 patients (36-month median follow-up). Accuracy was comparable across the four PVOI scores, with AUCs ranging from 0.70 to 0.74. All scores showed comparable ability to predict recurrent PE. When using the anatomical-based SqPVOI1, recurrence risk increased progressively with more proximal thrombus location: compared with segmental artery involvement (36-month cumulative incidence, 10.5%; n = 76), risk was 2- to 3-fold with lobar artery involvement (HR 2.90, 95%CI, 1.20-7.05, p = 0.005; 36-month cumulative incidence, 25.6%; n = 63) and 4- to 5-fold increased risk (HR 4.59, 95%CI, 1.85-11.42, p = 0.001; 36-month cumulative incidence, 46.8%; n = 41) with main pulmonary artery involvement.Simplified anatomical assessment of PVOI showed prognostic information comparable to quantitative indices. Further prospective validation is needed.

Patients with acute coronary syndrome (ACS) who have concurrent high ischemic and high bleeding risk are common after percutaneous coronary intervention (PCI), yet evidence guiding P2Y12 inhibitor selection remains limited. We compared ticagrelor and clopidogrel in ACS patients meeting OPT-BIRISK dual high-risk criteria after drug-eluting stent (DES) implantation.We retrospectively analyzed a single-center PCI registry. ACS patients undergoing new-generation DES implantation (March 2019-March 2022) who met both high ischemic and high bleeding risk criteria were classified by discharge P2Y12 inhibitor. Propensity score overlap weighting was adjusted for confounding. The primary endpoint was 12-month net adverse clinical events (NACE): all-cause death, myocardial infarction, stroke, or Bleeding Academic Research Consortium (BARC) type 3 or 5 bleeding.The final cohort comprised 20,213 dual high-risk patients (ticagrelor, 4,563 [22.6%]; clopidogrel, 15,650 [77.4%]). NACE was similar between groups (4.58% vs. 5.21%; adjusted hazard ratio [aHR], 1.05; 95% confidence interval [CI], 0.89-1.23; p = 0.568). Ticagrelor was not associated with reduced ischemic events (aHR, 0.90; 95% CI, 0.72-1.12; p = 0.333) but with higher BARC type 3 or 5 bleeding (2.17% vs. 1.57%; aHR, 1.39; 95% CI, 1.08-1.77; p = 0.009). In exploratory subgroup analysis, ticagrelor was associated with higher NACE in patients aged 75 years or older (p-Value for interaction = 0.04).In dual high-risk ACS patients undergoing DES implantation, discharge ticagrelor-based dual antiplatelet therapy was associated with higher bleeding risk without reducing NACE or ischemic events compared with clopidogrel. These observational findings support individualized P2Y12 inhibitor selection and warrant prospective confirmation.

Currently, no sensitive, widely available, rapid turnaround assays to measure the effect on coagulation of direct oral anticoagulants exist.The point-of-care ClotChek (Perosphere Technologies Inc.) coagulometer was developed to address this unmet need with high sensitivity and precision. This proof-of-concept study aimed to determine normal clotting time in healthy, non-anticoagulated subjects; summarize clotting times at trough and peak drug concentrations in patients taking apixaban and rivaroxaban; and identify cut-points that maximize both sensitivity and specificity for predicting whether an individual is meaningfully anticoagulated.In 141 normal subjects, the mean clotting time was 244.2 ± 25.8 seconds (median 244.0 seconds; range 183-296 seconds). In 39 patients on apixaban, mean clotting times were 293.9 ± 32.5 seconds at trough and 323.1 ± 27.9 seconds at peak. In 42 patients on rivaroxaban, mean clotting times were 287.8 ± 44.9 seconds at trough and 380.4 ± 41.2 seconds at peak. Strong positive correlations are seen between the anticoagulant drug response determined by the assay and anticoagulant drug levels for apixaban (Spearman's rho = 0.74, p < 0.0001) and for rivaroxaban (Spearman's rho = 0.82, p < 0.0001). ClotChek clotting times showed good sensitivity and specificity to identify meaningful anticoagulation (>75 ng/mL) among patients taking apixaban (AUC = 0.91, 83% sensitivity, 86% specificity) or rivaroxaban (AUC = 0.96, 91% sensitivity, 90% specificity). Similar results were seen using the lower threshold of >30 ng/mL.These results require clinical validation in further studies but suggest that the ClotChek assay could aid physicians at the point of care in making therapeutic decisions in patients with adverse events associated with oral factor Xa inhibitors.

Thrombocytopenia contributes to trauma-induced coagulopathy and may require platelet transfusion. Viscoelastic assays can provide rapid surrogates of platelet count, but thresholds may be influenced by physiological derangements. We compared ROTEM-derived parameters for diagnosing thrombocytopenia and tested their robustness across selected conditions.We performed a retrospective registry-based cohort study in a level 1 trauma center (2011-2021). Severely injured adults were included if they had at least one paired ROTEM and platelet count measurement within 24 hours of admission; patients receiving anticoagulants were excluded. Thrombocytopenia was defined as platelets <100 G/L. Associations between platelet count and ROTEM parameters were assessed with Spearman correlation. Diagnostic accuracy was evaluated using ROC and precision-recall (PR) analyses; optimal thresholds were chosen by maximal F1-score. For the best parameter, performance was explored across hemoglobin level, acidosis, and hypocalcemia.Of 4,395 admissions, 865 patients were included with 1,395 paired measurements; thrombocytopenia occurred in 213 samples (15.3%) and was present at admission in 35 (4%). Platelet count correlated with clot amplitude/elasticity (p < 0.001). The platelet component of clot amplitude at 5 minutes (A5 PLAT) had the best discrimination (AUC 0.929; AUPRC 0.627). The optimal PR-based threshold was A5 PLAT ≤21 mm. Performance was mainly affected by severe acidosis and severe hypocalcemia.In severe trauma, ROTEM-derived A5 PLAT accurately identifies platelet count <100 G/L and outperforms other ROTEM parameters, supporting its use for rapid platelet-related decision-making. Hypocalcemia and acidosis may reduce precision and should be considered when applying ROTEM-based thresholds during early trauma resuscitation.

Type 1 diabetes (T1D) is associated with prothrombotic changes that contribute to an elevated risk of cardiovascular disease. We hypothesised that insulin resistance (IR), increasingly prevalent among individuals with T1D, exacerbates haemostatic abnormalities through distinct proteomic alterations in plasma. In a cross-sectional observational study, citrated plasma was collected from individuals with T1D (with and without IR) and healthy controls. Fibrin clot formation and lysis were assessed using turbidimetric assays. Plasma proteomes were analysed using data-independent acquisition mass spectrometry (DIA-MS), and correlations between protein abundance and clinical parameters were evaluated. T1D plasma exhibited faster clot initiation, increased clot density, and impaired fibrinolysis. Effects on clot lysis were most pronounced in individuals with IR. DIA-MS revealed distinct proteomic signatures, with significant changes in proteins involved in regulating clot structure and breakdown. Notably, clot density correlated positively with fibrinogen gamma-chain abundance. T1D is characterised by prothrombotic alterations that are further intensified by IR. Our findings reveal that these changes are driven by proteomic shifts affecting clot initiation, structural integrity, fibrinolysis, and inflammatory pathways, offering mechanistic insights and potential targets for mitigating cardiovascular risk in this population.

Bruton tyrosine kinase (Btk) is an intracellular enzyme belonging to the Tec family tyrosine kinases. Initially identified for its role in B cell signaling, it has now emerged as a pivotal mediator in thrombosis and cardiovascular diseases (CVD). Beyond its established role in B cell malignancies, Btk is expressed in platelets, macrophages, neutrophils, and other innate immune cells, orchestrating platelet activation, atherothrombosis, venous thrombosis, immunothrombosis/thrombo-inflammation, and vascular inflammation. Patients with X-linked agammaglobulinemia (XLA), genetically lacking Btk, do not bleed, indicating that selective platelet Btk inhibition may provide a safe antithrombotic strategy. Indeed, highly selective Btk inhibitors (BTKi) show no or only minor bleeding in autoimmune disease trials, and rilzabrutinib, approved in 2025, reduces bleeding in patients with immune thrombocytopenia (ITP). This executive summary of a recent state-of-the-art review synthesizes current understanding of Btk's mechanistic contributions to thrombosis and CVD, evaluates the evolution of BTKi, and explores their therapeutic potential.

Ticks have evolved a diverse repertoire of salivary proteins that enable prolonged blood feeding by finely modulating host hemostatic, vascular, and immune responses, providing an unexpected source of candidates for cardiovascular and anti-inflammatory therapy. Tick saliva contains molecules that interfere with vasoconstriction, platelet activation, coagulation and fibrinolysis, while at the same time shaping leukocyte recruitment and cytokine release, placing these proteins at the crossroads of hemostasis, inflammation and cardiovascular disease. In this review, the main families of tick-derived effectors are discussed, including thrombin and factor Xa inhibitors, apyrases, serpins, and multispecific proteins that act on both coagulation and inflammatory pathways, with an emphasis on how their mechanisms could be harnessed for anti-thrombotic and anti-inflammatory therapies. Particular attention is given to salp proteins and the chemokine-binding evasins, which remodel chemokine networks and immune cell trafficking in models of atherosclerosis, ischemia-reperfusion injury and stroke, where they can dampen leukocyte infiltration, matrix degradation and plaque destabilization. Taken together, these insights show how millions of years of tick-host coevolution have produced a molecular toolkit that not only clarifies fundamental aspects of thromboinflammation, but also provides a basis for next-generation biologics targeting cardiovascular and inflammatory disorders.