Antiphospholipid syndrome (APS) is a prothrombotic autoimmune disorder associated with venous thromboembolism (VTE) and chronic thromboembolic pulmonary hypertension (CTEPH). Current guidelines recommend APS screening in CTEPH patients. The exact prevalence of APS in both CTEPH and chronic thromboembolic pulmonary disease (CTEPD) without pulmonary hypertension (PH) remains unclear. Although recently increasing attention has been directed toward treatment outcomes following pulmonary endarterectomy (PEA), other CTEPD without PH patients and those treated with alternative interventions, such as balloon pulmonary angioplasty or PH medication, remain insufficiently studied. This study aimed to assess the prevalence, lesion distribution, and outcomes of APS in CTEPH and CTEPD without PH. We retrospectively analyzed 259 patients diagnosed with CTEPH (n = 233) or CTEPD without PH (n = 26) at a tertiary care referral center in the Netherlands. Demographic, clinical, hemodynamic, laboratory, and follow-up data were collected from medical records. Lesion distribution in APS patients was related to literature. In 140 out of 259 patients, APS testing results could be retrieved. Among these, 112/140 (80%) had no APS, 19/140 (14%) tested positive without repeated confirmation or without APS clinical criteria, and 9/140 (6%) were classified as APS. Of the nine APS patients, four had a triple antibody profile. APS patients were relatively young (mean age 44 years), often had autoimmune comorbidities (3/9; 33%) and a history of recurrent VTE (6/9; 67%). All APS patients experienced mild thrombocytopenia post-PEA. Both proximal (5/9; 56%) and distal disease (6/9; 67%) were observed in APS. This study provides a real-world overview of CTEPH/CTEPD without PH patients with and without APS and contributes to the limited literature on this specific patient population.
Abdominal Aortic Aneurysm (AAA) is characterized by persistent inflammation, extracellular matrix loss, and intraluminal thrombus formation, yet the genetic links among these processes remain incompletely defined. Here, we examine evidence that genetic variation can influence inflammatory and thrombotic responses at the same time. Findings from genome-wide association studies are considered alongside transcriptomic, proteomic, single-cell, epigenetic, and experimental data. Particular attention is given to candidate genes and signaling networks relevant to AAA susceptibility, enlargement, and rupture. The available evidence supports a model in which inherited susceptibility alters the balance between vascular inflammation, coagulation, fibrinolysis, and wall repair. However, many reported loci still lack functional confirmation, and most genetic data come from populations of European ancestry. Defining the causal variants and the cells in which they act will be necessary before these findings can be used for individualized screening or treatment.
Introduction Predicting bleeding in hemophilia A is difficult due to limitations of existing factor VIII (FVIII) activity assays, which correlate poorly with clinical bleeding tendency. Measurement of thrombin generation (TG) by calibrated automated thrombography (CT) may be an alternative to predict bleeding as it measures an individual's complete plasma derived coagulation potential, rather than just focusing on one part of the coagulation cascade. However, lack of standardization limits its applicability. Objective To evaluate the ability of our standardized tissue factor (TF)/factor XI (FXI) a dual-activated thrombin generation assay (TGA) to assess TG across severe, moderate, and mild hemophilia A. Secondarily, we evaluate whether varying TG levels at similar FVIII concentrations translate to different clinical bleeding tendencies. Materials and Methods Plasma samples from 657 adult patients with hemophilia A of all severities included in the Hemophilia in the Netherlands 6 (HiN6) study were used. Samples were collected through standardized protocols from six Dutch hemophilia treatment centers, and stored in a centralized biobank. FVIII activity was centrally measured using one-stage assays. Thrombin generation was measured using our in-house TF/FXIa TGA protocol using 1 pm TF, 100 pm FXIa, and 30 μM phospholipids. Bleeding tendencies were analyzed based on patient questionnaires. Results The TF/FXIa dual-activated TGA protocol was able to measure thrombin generation across all severities of hemophilia A. Median peak heights (PH) were 119.5, 98.9, and 214.7 nM for severe, moderate, and mild, respectively. Moreover, the assay showed substantial variation in interindividual TG levels among patients with comparable FVIII activity levels (coefficient of variance of 99%, 83%, and 47% for severe, moderate, and mild hemophilia A, respectively). However, TG did not differentiate between patients with and without self-reported bleeding in this study. Conclusion The standardized TF/FXIa dual-activated TGA represents a tool for assessing individual coagulation potential in hemophilia A. More research is needed to further characterize the interindividual differences in thrombin generations at similar FVIII levels and possibly link these results to bleeding tendency.
Heparin-induced thrombocytopenia (HIT) with thrombosis typically necessitates immediate therapeuticdose anticoagulation, yet management becomes exceedingly complex when a profound bleeding risk coexists. We report a unique case of serologically confirmed HIT developing during low-molecularweight heparin prophylaxis following major trauma in a 67-year-old man. On day 10 of heparin exposure, the patient presented with platelet count declining from 169×10⁹/L to 20×10⁹/L (91% reduction), hypofibrinogenemia (1.12 g/L), extensive deep vein thrombosis, and pulmonary embolism. Owing to extreme bleeding risk, argatroban initiation was deferred for 48 hours post-diagnosis, then cautiously titrated from 0.08 to 0.67 μg/kg/min guided by dynamic coagulation-fibrinolysis markers (thrombinantithrombin complex, plasmin-α2-antiplasmin complex, and D-dimer). These markers provided realtime assessment of treatment response, declining substantially prior to platelet count normalization. By day 12 post-diagnosis, platelet count recovered to 176×10⁹/L, permitting successful definitive orthopedic surgery on day 13 without bleeding complications. This case illustrates that in HIT with lifethreatening thrombosis and extreme bleeding risk, an individualized "start low, go slow" argatroban strategy with delayed initiation achieves effective anticoagulation while minimizing hemorrhagic risk.
Chimeric antigen receptor (CAR) T cell therapy has transformed the management of hematologic malignancies, yet its clinical success is tempered by severe immune-mediated toxicities, including cytokine-release syndrome (CRS) and immune effector cell-associated neurotoxicity syndrome (ICANS), often accompanied by CAR T cell therapy-related coagulopathy (CARAC). Converging evidence identifies therapy-related endotheliopathy as a central pathophysiological link between cytokine excess, hemostatic dysregulation, capillary leak, and organ injury. Parallel efforts aim to identify circulating biomarkers that can signal emerging toxicity before clinical deterioration. This review summarizes the biological basis of endotheliopathy during CAR T cell therapy, with particular emphasis on two interconnected regulatory systems: the von Willebrand factor (VWF)/ADAMTS13 axis, which governs platelet adhesion and microvascular thrombosis, and the angiopoietin (Ang)-tyrosine kinase receptor Tie2 signaling pathway, which regulates endothelial stability and vascular permeability. Dysregulation of these pathways drives the shift from adaptive immunothrombosis to pathological endothelial injury, characterized by loss of anticoagulant control, barrier disruption, and microvascular instability. Clinical studies show that alterations in the VWF/ADAMTS13 balance and increases in the Ang-2/Ang-1 ratio correlate with CRS and ICANS severity and may precede overt toxicity, highlighting their potential as markers of endothelial vulnerability. Defining actionable biomarker thresholds and evaluating endothelial-targeted interventions are key priorities for improving the safety and precision of CAR T cell therapy.
Objective Clinical trials indicate that avatrombopag, a thrombopoietin-receptor agonist (TPO-RA), is safe and effective for treating patients with primary immune thrombocytopenia (ITP), but real-world evidence on its broader clinical effectiveness is limited. Methods This European multi-center retrospective chart review included adults with primary ITP treated with avatrombopag in routine clinical practice, who had medical records available for ≥ 12 weeks before and after avatrombopag initiation. Results Data from 76 patients with ITP (51 TPO-RA naïve, 25 prior TPO-RA exposed) showed a median time of 4.2 years (interquartile range: 0.7-10.3) from ITP diagnosis to avatrombopag initiation (index date) and a median follow-up of 15.9 months (interquartile range: 7.8-22.8). By week 12, 96 and 93% of the cohort achieved platelet counts (PC) of ≥30 × 10 9 /L and ≥50 × 10 9 /L, respectively; 72% had a complete response (≥100 × 10 9 /L) by week 12, 80% by week 26, and 87% by week 52 postindex. PC reached ≥30 × 10 9 /L, ≥50 × 10 9 /L, and ≥100 × 10 9 /L in a median of 8 (95% confidence interval: 7-12), 10 (8-14), and 19 (12-23) days from the index date, respectively. At 1 year, 75% ( n total = 34) and 47% ( n total = 21) maintained PC of ≥50 × 10 9 /L and ≥100 × 10 9 /L, respectively. Avatrombopag was permanently discontinued by 19 patients (25%), including 7 (37%) due to being candidates for sustained remission off-treatment. Thromboembolic rates were 4.9 (95% confidence interval: 1.3-12.5) per 100 patient-years during follow-up. The incidence rate (95% confidence interval) of ITP-related outpatient visits and inpatient admissions was 8.9 (8.2-9.5) and 0.1 (0.1-0.2) per person-year. Conclusion This study supports clinical trials' findings and other postmarketing evidence demonstrating the effectiveness of avatrombopag.
Background Platelet agonists responses in vitro (i.e., reactivity) include the creation of phosphatidylserine (PS)-exposing platelets together with the activation of the fibrinogen receptors (α IIb β 3 ) and lysosomal exocytosis. It is feasible to judge the activation pathways by analyzing platelet surface annexin V, the activated fibrinogen receptor (PAC-1), and the release of lysosomal-associated membrane protein (LAMP-1), correspondingly. We postulate that, in type 2 diabetes (T2DM), surface PS of circulating platelets, unprovoked in vitro , links with whole blood (WB) agonist-induced responses. Patients and Methods After informed consent, T2DM subjects ( n = 35) were enrolled. A Percoll gradient (1.09-1.04 kg/L) separated their normal-sized platelets according to density into subpopulations ( n = 8). A flow cytometer analyzed surface annexin V (mean fluorescence intensity [MFI]) of the subfractions, unprovoked ex vivo. The datasets were subsequently correlated with platelet WB agonist-induced responses (i.e., annexin V, PAC-1, and LAMP-1 [all MFI]) to α-thrombin (10 μM), cross-linked collagen-related peptide (CRP-XL, 0.15 μg/mL), and adenosine diphosphate (ADP, 5 μM) in vitro. Results Surface annexin V (MFI) of most platelet subfractions and the magnitudes of WB agonist-induced annexin V (MFI) of normal-sized platelets in vitro associated closely. Such PS-expressing platelets also linked inversely with WB agonist-evoked surface PAC-1 (MFI) (all used agonists) and LAMP-1 (MFI) (CRP-XL, ADP only). It is concluded that surface PS, unprovoked in vitro, of most density-separated platelets connected with platelet reactivity, i.e., their WB agonist-evoked reactions in the test tube.
Background Fibrinolysis is essential for maintaining hemostatic balance, and disturbances contribute to bleeding and thrombotic disorders. Rotational thromboelastometry modified with tissue plasminogen activator (ROTEM-tPA) enables dynamic assessment of fibrinolytic capacity and may support diagnostic and prognostic evaluation in clinical settings. The assay has been widely used in clinical research, but the lack of reference intervals in healthy individuals limits standardized interpretation and clinical implementation. Methods We included 122 healthy plasma donors aged 20-69 years with equal sex distribution. Citrated whole blood samples were analyzed using a standardized ROTEM-tPA protocol with exogenous tissue plasminogen activator (tPA) activation (125 ng/mL). Reference intervals were calculated using a non-parametric approach with 90% confidence intervals in accordance with the Clinical and Laboratory Standards Institute (CLSI) EP28-A3c guidelines. Analytical repeatability (coefficients of variation) and associations with age and sex were also evaluated. Results ROTEM-tPA parameters demonstrated consistent performance across age groups and sex. Analytical repeatability was high, reflected by low coefficients of variation. Reference intervals were established for all ROTEM-tPA parameters. For key parameters, reference intervals were clotting time: 45-68 s, amplitude at 10 min: 33-56 mm, maximum clot firmness: 34-61 mm, lysis index at 30 min: 0-97%, lysis index at 45 min: 0-50%, maximum lysis: 92-100%, area under the curve: 3429-6025 mm·100, lysis time: 1412-3211 s, lysis onset time: 720-2182 s, fibrinolysis speed: 2 to 6 mm/min, and time to area under the curve initiation: 404-1314 s. Conclusion We established the first comprehensive reference intervals for ROTEM-tPA in a healthy adult population. These data provide a foundation for standardized interpretation of fibrinolytic dynamics and support clinical application of ROTEM-tPA in bleeding and thrombotic disorders.
Objectives: To assess effectiveness of recombinant factor VIII Fc fusion protein (efmoroctocog alfa; referred to herein as rFVIIIFc) prophylaxis in people with haemophilia A (PwHA) stratified by age, body mass index (BMI), disease severity and inhibitor history included in the A-SURE (NCT02976753) and PREVENT (NCT03055611) real-world studies. Methods: PwHA receiving at least one prescription of rFVIIIFc and ≥3 months follow-up during the prospective periods were included. Post-hoc analyses were performed for the overall analysis population and subgroups based on age, BMI, disease severity and those with and without previous inhibitors. Effectiveness endpoints were annualised bleeding rate (ABR), annualised joint bleeding rate (AjBR), injection frequency and factor consumption in the prospective period. Results: Overall, 333 PwHA were analysed. ABRs and AjBRs, generally, were low across the different subgroups (range of medians, 0.0–0.6 for both ABRs and AjBRs, except for ABRs in PwHA aged ≥65 years). Injection frequencies (n injections/week) were comparable across subgroups (range of medians, 2.0–2.3), and factor consumption was generally similar (range of medians, 68.3–100.0 international units/kg/week), though with slightly higher factor consumption in paediatric PwHA and lower consumption in the overweight or obese BMI groups. Conclusions: These post-hoc analyses support the effectiveness and, therefore, use of rFVIIIFc prophylaxis in PwHA across all ages, BMI categories, severities and for those with a history of inhibitors. Trial registration: ClinicalTrials.gov. A-SURE: NCT02976753; PREVENT: NCT03055611
Background:Platelets and certain immune cells contain releasable granules that play essential roles in hemostasis and immune regulation. However, the regulatory mechanisms governing degranulation of platelets versus immune cells remain incompletely understood. Objectives:This study aimed to elucidate the distinct regulatory mechanisms underlying granule release in platelets and immune cells. Methods:Mouse platelets were freshly isolated from peripheral blood, neutrophils were purified from bone marrow, and mast cells were generated from bone marrow progenitors by in vitro differentiation. The effects of phorbol ester (PMA), ionomycin, and their combination on degranulation of platelets, neutrophils, and mast cells were examined. In addition, pharmacological inhibitors targeting key components of multiple signaling pathways were used to investigate the molecular mechanisms regulating degranulation of these three cell types. Results:PMA and ionomycin strongly induced α-granule release of platelets, whereas only moderately stimulating dense-granule secretion. For neutrophils, PMA and ionomycin each triggered moderate azurophilic-granule release, whereas their combination markedly enhanced degranulation. In contrast, PMA alone failed to induce mast cell degranulation, ionomycin robustly stimulated granule release, and their combination further amplified ionomycin-induced response. Mechanistically, thrombin-induced platelet degranulation was inhibited exclusively by phospholipase C (PLC) and protein kinase C (PKC) inhibitors. Zymosan-induced neutrophil degranulation was suppressed by inhibitors of phosphoinositide 3 kinase, spleen tyrosine kinase (SYK), Bruton's tyrosine kinase (BTK), mitogen-activated protein kinase 1/2 (MEK1/2) and P38 but was enhanced by PLC and PKC inhibition. Mast cell degranulation induced by IgE and antigen was significantly inhibited by the inhibitors targeting SYK, BTK, PLC, and PKC. Conclusion:These findings reveal substantial differences in the regulatory pathways controlling degranulation in platelets and immune cells. Such distinctions highlight the opportunities for the development of cell type-selective inhibitors to modulate degranulation, providing potential therapeutic strategies for thrombotic diseases and immune-related diseases.
Background:Incomplete thromboxane suppression with 81 mg aspirin daily is common and predicts higher vascular risk. We compared the effects of aspirin in controls and patients with cardiovascular disease and tested strategies to improve thromboxane suppression. Methods:Two-phase randomized, open-label pharmacodynamic study. In Phase 1, controls and patients received enteric-coated (EC) aspirin 81 mg daily for 3 weeks. In Phase 2, the best responders within each cohort were randomized to EC aspirin 81 mg daily, EC aspirin 81 mg alternate daily, or soluble aspirin 81 mg daily, and the poorest responders to EC aspirin 81 mg daily, 325 mg daily, or 162 mg twice daily. Where results with EC and soluble aspirin 81 mg daily were similar, these arms were pooled for comparisons of daily versus alternate daily dosing. Outcome measures were light transmission aggregation in response to arachidonic acid, adenosine diphosphate, and collagen; serum thromboxane B2 (sTXB2); and urinary 11-dehydro-thromboxane B2 (uTXB2; creatinine-normalized). Results:We enrolled 136 controls and 115 patients. Among controls, EC aspirin 81 mg daily suppressed platelet aggregation and reduced sTXB2 from 238.4 to 2.7 ng/mL and uTXB2 from 112.0 to 39.0 ng/mmol creatinine (all p < 0.0001). After 3 weeks, aggregation and serum thromboxane were similar in controls and patients but uTXB2 remained higher in patients (46.5 vs. 39.0, p = 0.004). In Phase 2, different aspirin formulations, doses, and dose frequencies did not materially affect platelet aggregation. In the best responders, EC and soluble aspirin had similar effects on thromboxane, but sTXB2 levels were higher with alternate daily versus daily dosing (pooled EC and soluble) in both controls (8.1 vs. 2.2 ng/mL, p = 0.005) and patients (5.2 vs. 1.7 ng/mL, p = 0.048). In the poorest responders, EC aspirin 162 mg twice daily produced the greatest suppression of both sTXB2 and uTXB2, with intermediate suppression with EC aspirin 325 mg daily and the least with EC aspirin 81 mg daily (all trend P values <0.05). Conclusion:Daily low-dose aspirin suppresses aggregation and serum thromboxane, but urinary thromboxane metabolites are less completely suppressed in patients with established cardiovascular disease. Alternate daily dosing attenuates thromboxane suppression, whereas divided dosing improves suppression in the poorest responders.
Background:Patients with venous thromboembolism (VTE) frequently require vitamin K antagonists (VKAs) to treat and prevent recurrent events. Aims:We performed a study to assess the quality of anticoagulation in patients with VTE treated with VKAs using time in therapeutic range (TTR), to identify associated factors with predictors of poor control and outcomes in VTE patients. Methods:We performed an observational, retrospective study that included VTE patients treated with VKA. The primary outcome was the TTR calculated according to the Rosendaal algorithm. Results:A total of 171 VKA-treated patients were evaluated (53.2% men). The average age of our patients at diagnosis was 49.8 + 16.6 years [17-92]. VTE's most common location was the lower limbs, with 91.8% cases, proximal in 83.6%. Patients were followed for a mean period of 178 days. The mean TTR was 41.2% (standard deviation: 32.9%), and 74.3% of the patients had a mean TTR < 65%. The rates of major bleeds and thromboembolic events were 0.5 and 2.2%, respectively. After multivariate statistical analysis, age older than 65 and surgery provoked VTE were associated with better TTR. Conclusions:These results are informative and may help identify patients who require closer monitoring or innovative strategies to optimize oral anticoagulant therapy outcomes.
DNA methylation modifies nucleotides, regulating gene expression without sequence change. The effects of DNA methylation within blood cell lineages on the development and function of endomitotic high DNA copy megakaryocytes (MKs) to anucleate platelets remain poorly understood. We sought to characterize this potential relationship by investigating associations between platelet function and methylation in circulating nucleated blood cells. Data were measured in the Framingham Heart Study Third Generation cohort ( n = 1,314). Five bioassays assessed platelet function in response to up to seven agonists in whole blood and platelet-rich plasma, and the Illumina 450K array was used to conduct an epigenome study of blood DNA methylation. In adjusted statistical association models, we found 46 significant associations (false discovery rate-adjusted p < 0.05) across 36 genomic DNA methylation sites, including cg24267699 in a putative regulatory site -742/-743 bases upstream from the ABO transcription start site associated with ristocetin platelet agglutination ( β = 0.21, standard error = 0.03, p < 1.04E-11). The 36 sites collectively reside within genes acting as transcription factors, genes implicated in granule release and exocytosis, cytoskeletal functions, mitochondrial function, and platelet function. The set of associated cytosine-phosphate-guanines was enriched in MKs for markers of regulatory activity, including DNase-I hypersensitivity sites and histone activity. Overall, we report in the first such epigenome scan that blood cell DNA methylation appears to be significantly associated with several platelet reactivity traits, and may drive the regulation of key genes involved in those processes presumably at the upstream level of hematopoietic stem cells or megaerythroid lineage cells.
Background: Antiphospholipid syndrome (APS) is an autoimmune disease characterized by the persistent presence of antiphospholipid antibodies (aPL), mainly targeted against β2 glycoprotein 1 (β2GP1). The autoimmune response to β2GP1 is aimed at several B cell and T cell epitopes. Molecular mimicry of these epitopes by gut commensal proteins, so-called mimotopes, causing cross-immunization might contribute to the formation of aPL. Objective: To study the potential role of gut microbiome cross-immunization in APS by examining cross-reactivity of aPL with gut commensal mimotope containing proteins. Methods: Fecal microbial metagenome of APS patients was determined using shotgun sequencing. An in-house developed in silico pipeline was used to identify gut commensal proteins that show sequence homology with known β2GP1 B and T cell epitopes in the metagenomic data. An enzyme-linked immunosorbent assay was used to test the identified microbial proteins for IgG cross-reactivity, with plasma of 21 APS patients and 17 control participants. Results: The in silico pipeline resulted in the identification of six gut commensals with a B cell and T cell β2GP1 epitope homologue. Of these, YjjG family noncanonical pyrimidine nucleotidase, one of the candidate-β2GP1 B cell mimicking proteins, showed significantly increased IgG reactivity in APS patients compared to control participants, as well as higher binding of a specific anti-β2GP1 monoclonal antibody than a negative control. Conclusion: Our study shows reactivity of IgG antibodies to YjjG family noncanonical pyrimidine nucleotidase from Roseburia amylophila in APS patients. Insights into the origins of antibody formation may yield new therapeutic targets for improvement of APS treatment.
Chronic coronary syndrome (CCS) represents a heterogeneous and dynamic manifestation of coronary artery disease characterized by persistent atherosclerotic burden and ongoing risk of atherothrombotic events. Antithrombotic therapy remains a cornerstone of secondary prevention in CCS, yet optimal treatment strategies have evolved substantially in recent years. The 2024 European Society of Cardiology (ESC) guidelines provide updated recommendations that reflect emerging evidence from randomized clinical trials and meta-analyses evaluating antiplatelet and anticoagulant strategies. This narrative review summarizes key updates in the 2024 ESC CCS guidelines and the clinical evidence underpinning these changes. Contemporary management has moved beyond a uniform antithrombotic approach toward individualized treatment strategies based on ischemic and bleeding risk. Single antiplatelet therapy remains the foundation of long-term management, although clopidogrel is now recognized as a Class I, Level A alternative to aspirin in selected patients. For patients undergoing percutaneous coronary intervention (PCI), the guideline maintains a default strategy of 6 months of dual antiplatelet therapy (DAPT) while providing stronger recommendations for abbreviated DAPT in patients at high bleeding risk. Emerging evidence supporting de-escalation strategies and early aspirin withdrawal following PCI has further contributed to risk-adapted treatment pathways. Conversely, in patients with persistently high ischemic risk and low bleeding risk, intensified strategies-including prolonged DAPT, ticagrelor-based therapy, or dual pathway inhibition with low-dose rivaroxaban and aspirin-may provide additional protection against recurrent ischemic events. The updated recommendations underscore the importance of patient-centered risk stratification and periodic reassessment of ischemic and bleeding risk. Integrating clinical judgment with structured tools such as ARC-HBR and PRECISE-DAPT enables clinicians to tailor antithrombotic therapy in CCS, optimizing net clinical benefit in routine practice.
Background:The diagnostic evaluation of pulmonary embolism (PE) in pregnancy is challenging, as the physiologic changes of pregnancy can mimic several PE symptoms. Acute respiratory infections introduce additional diagnostic complexity by producing systemic inflammation, altering vital signs, and, in some cases, elevating D-dimer levels. As a case in point, we examined how SARS-CoV-2 infection affected presentation, pretest probability, and diagnostic testing in pregnant patients with possible PE. Methods:We performed a retrospective cohort study across 21 community medical centers from October 1, 2021, to March 30, 2023. We included pregnant outpatients ≥ 18 years evaluated for suspected PE with D-dimer testing, compression ultrasonography, computed tomography pulmonary angiography (CTPA), or lung scintigraphy. We compared patients with and without COVID-19 using bivariate analysis. Results:Among 860 patients, the median age was 30.0 years; 39.1% were in the third trimester. COVID-19 was present in 147 (17.1%). Compared with non-COVID-19 patients, those with COVID-19 more often had fever (36.1% vs. 4.2%), tachycardia ≥ 110 bpm (66.0% vs. 34.2%), and oxygen saturation < 95% (12.2% vs. 4.8%), but less often reported chest pain (49.7% vs. 65.5%; all p < 0.001). Nearly all patients had low-to-intermediate pretest probability, but intermediate classification was more common with COVID-19 patients (63.3% vs. 39.0%; p < 0.001). COVID-19 patients more often had elevated D-dimer > 1.0 mg/L (49.1% vs. 36.4%; p < 0.001) and more commonly underwent chest radiography (61.9% vs. 50.1%; p = 0.009). Among patients who underwent advanced imaging ( n = 393), CTPA predominated in both cohorts. Overall, PE was rare ( n = 6; 0.7%), and mortality was low ( n = 3; 0.3%). Conclusion:COVID-19 in pregnancy was associated with worse vital signs, higher pretest probability, higher D-dimer values, and increased diagnostic testing. These findings illustrate how acute respiratory infections may recalibrate PE risk assessment in pregnancy and highlight the need to refine diagnostic strategies when infection-related physiologic changes are present.
Background:Although the incidence of thromboembolic events after catheter ablation for atrial fibrillation (AF) is low, the residual risk persists. The nature of these long-term events remains poorly characterized, and optimal risk stratification is challenging. We therefore aimed to characterize the postablation ischemic events and develop an enhanced risk stratification model. Methods:This single-center historical cohort study enrolled 1,163 patients who underwent initial AF ablation. The primary endpoint was a composite of postdischarge ischemic events (ischemic stroke, transient ischemic attack, and systemic arterial thromboembolism [SE]). The predictability of clinically available risk scores and individual parameters, including left atrial volume index (LAVI), was assessed. The new model combining the strongest predictors was benchmarked against the risk score alone. Results:Over a median follow-up of 5.1 (interquartile range: 3.1-7.1) years, 24 patients (2.1%) experienced an ischemic event (incidence: 0.38 per 100 person-years [95% confidence interval, 0.24-0.57]). AF-related etiologies (cardioembolic stroke/SE) accounted for 42% of events. More than half of the events (54%) occurred when the patients were in sinus rhythm. CHA 2 DS 2 -VASc score and LAVI were the strongest predictors. A combined model incorporating both parameters showed numerically higher discrimination and modest improvement in reclassification (net reclassification improvement: 0.698 [0.300-1.095], p < 0.001) and discrimination (integrated discrimination improvement: 0.009 [0.002-0.017], p = 0.014) compared with the CHA 2 DS 2 -VASc score alone. Conclusion:In this long-term analysis, postablation ischemic events were infrequent and of mixed etiology, with noncardioembolic causes being common. A combined model integrating CHA 2 DS 2 -VASc and LAVI showed modest incremental value for residual risk stratification.
