Journal of Thrombosis and Haemostasis最新文献

{"title":"Sex-specific DNA methylation marks associated with sex-biased risk of recurrence in unprovoked venous thromboembolism.","authors":"Ohanna C L Bezerra, Marc Rodger, Gaëlle Munsch, Michael J Kovacs, Grégoire Le Gal, Pierre E Morange, David-Alexandre Trégouët, Celia M T Greenwood, France Gagnon","doi":"10.1016/j.jtha.2025.01.004","DOIUrl":"https://doi.org/10.1016/j.jtha.2025.01.004","url":null,"abstract":"<p><strong>Background: </strong>Whether to stop oral anticoagulants after a first unprovoked venous thromboembolism (VTE) is challenging, partially due to an intriguingly higher risk of VTE recurrence (rVTE) in men after therapy discontinuation. DNA methylation (DNAm) differences between men and women might underly this sex-biased rVTE risk difference.</p><p><strong>Aim: </strong>To investigate sex-specific associations between DNAm at cytosine-phosphate-guanine (CpG) sites and rVTE.</p><p><strong>Methods: </strong>In 417 unprovoked VTE patients, including 101 experiencing recurrences over 5-year follow-up (REVERSE I), we analyzed blood DNAm using the Illumina EPIC array and performed a sex-stratified epigenome-wide association study. We further examined 181 major provoked VTE patients, including 36 recurrences over 14-year follow-up (MARTHA), to investigate whether DNAm are risk factors for rVTE after anticoagulation therapy.</p><p><strong>Results: </strong>Hypomethylated CpGs at genes TBC1D22B-cg01060850 and ZHX2-cg07808424 in men and DIP2B-ch.12.1038646R and DENND3-cg03401656 in women were associated with rVTE at genome-wide level (p<7e-8). Though not statistically significant, DENND3-cg03401656 had the same direction of effect in MARTHA women. Sensitivity analysis confirmed the robustness of the estimates including potential confounders, adaptations of the Cox model, non-Europeans, and proximal methylation quantitative trait loci (meQTLs) in the association. The associated CpGs were situated at genes for membrane trafficking, corroborating the participation of Rab regulatory proteins in rVTE, and transcription factors.</p><p><strong>Conclusions: </strong>We identified DNAm marks as potential risk factors for sex-biased recurrence in unprovoked VTE. Further replication and experimental validation could refine our understanding on the regulation of the identified DNAm sites and help optimize personalized decision-making for long-term anticoagulation after first VTE.</p>","PeriodicalId":17326,"journal":{"name":"Journal of Thrombosis and Haemostasis","volume":" ","pages":""},"PeriodicalIF":5.5,"publicationDate":"2025-01-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143029106","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Exosite crosstalk in thrombin.","authors":"James C Fredenburgh, Jeffrey I Weitz","doi":"10.1016/j.jtha.2025.01.003","DOIUrl":"https://doi.org/10.1016/j.jtha.2025.01.003","url":null,"abstract":"<p><p>Thrombin is the central mediator of hemostasis, where it converts fibrinogen to fibrin, activates upstream factors to promote coagulation, activates factor XIII and thrombin-activatable fibrinolysis inhibitor to stabilize fibrin, mediates anticoagulation, and modulates cellular activity via cell surface receptors. Thus, regulation of thrombin activity is essential to the hemostatic balance. Thrombin is regulated by positively charged surface domains that surround the active site. These exosites bind substrates, inhibitors, cofactors, and receptors that coordinate to direct thrombin to the appropriate location and modulate catalytic activity. Thus, the exosites are essential to the activity and regulation of thrombin. In addition to acting as binding sites, the exosites modulate the active site allosterically. Furthermore, the exosites impact each other, whereby the binding of ligands to one exosite impacts the function of the opposing exosite. Given the integral role that exosites play in the regulation of thrombin, they are attractive targets for the regulation of thrombin; they are attractive targets for the development of new anticoagulants.</p>","PeriodicalId":17326,"journal":{"name":"Journal of Thrombosis and Haemostasis","volume":" ","pages":""},"PeriodicalIF":5.5,"publicationDate":"2025-01-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143023948","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Prolonged versus standard thromboprophylaxis in oesophageal cancer patients undergoing surgery: A randomised, controlled study.","authors":"Tua Gyldenholm, Nina Madsen, Niels Katballe, Daniel Willy Kjær, Thomas Decker Christensen, Anne-Mette Hvas","doi":"10.1016/j.jtha.2025.01.002","DOIUrl":"https://doi.org/10.1016/j.jtha.2025.01.002","url":null,"abstract":"<p><strong>Background: </strong>Recent guidelines recommend prolonged thromboprophylaxis after oesophagectomy due to cancer. However, no previous studies have examined if prolonged prophylaxis is superior to standard, in-hospital prophylaxis. We aimed to perform the first clinical, randomised study testing the efficacy of a prolonged, one-month thromboprophylaxis with low molecular weight heparin versus the standard treatment.</p><p><strong>Methods: </strong>The study was an open-label, randomised, controlled trial including patients undergoing oesophagectomy. The primary endpoint was the difference in prothrombin fragment 1+2 (F1+2) levels one month after surgery between the standard and the intervention group. The secondary endpoints were incidence of venous thromboembolic events and mortality.</p><p><strong>Results: </strong>The study was terminated before reaching the expected sample size of 100 patients due to low accrual. We included 79 patients. At follow-up one month after surgery, F1+2 levels did not differ between the standard and the intervention group (p=0.41). Incidence of venous thrombosis was similar in the two groups with 13% in the standard and 15% in the intervention group. Preoperative F1+2 levels were significantly higher in patients who developed a venous thrombosis within one month after surgery than in those who did not (p=0.01). The odds ratio of VTE per 50 pmol/L increase in F1+2 was 1.64 (95% CI 1.17-2.54). No patients died within one month after surgery.</p><p><strong>Conclusions: </strong>No benefit of prolonged thromboprophylaxis after oesophagectomy was found. Preoperative F1+2 levels were found to be a predictor for incidence of postoperative thromboembolism.</p>","PeriodicalId":17326,"journal":{"name":"Journal of Thrombosis and Haemostasis","volume":" ","pages":""},"PeriodicalIF":5.5,"publicationDate":"2025-01-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143023949","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Intravenous tenecteplase bridging reperfusion ameliorates cerebral ischemia/reperfusion injury by improving microvascular circulation in rats.","authors":"Yue-Xin Ning, Ji-Ru Cai, Ting-Ting Wang, Yi-Han Wang, Yu Cui, Hui-Sheng Chen","doi":"10.1016/j.jtha.2024.12.042","DOIUrl":"https://doi.org/10.1016/j.jtha.2024.12.042","url":null,"abstract":"<p><strong>Background: </strong>Endovascular treatment (EVT) alone was not demonstrated to be non-inferior to intravenous alteplase bridging EVT in acute large vessel occlusion (LVO) stroke. Using cerebral ischemia/reperfusion (I/R) injury model, intravenous tenecteplase (TNK) was administrated after ischemia followed by reperfusion at various time points.</p><p><strong>Objectives: </strong>To investigate whether intravenous TNK bridging EVT vs EVT alone could improve I/R injury, and this effect may be associated with the time from TNK to reperfusion.</p><p><strong>Methods: </strong>Rats received intravenous TNK (1.4 mg/kg) or vehicle (sterile water) 1.0 hour after middle cerebral artery occlusion (MCAO), followed by reperfusion after 0.5 or 1.0 hour following TNK. Neurological deficit scores, infarct volume, and brain edema were measured at 24 hours after MCAO. Microthrombi were determined by immunofluorescence staining for CD31⁺/fibrinogen⁺ and CD31⁺/thrombocyte⁺. Inflammatory cell infiltration in the ischemic brain region was determined by flow cytometry.</p><p><strong>Results: </strong>Compared with vehicle, TNK significantly reduced neurological deficit scores, brain infarction, neuro-inflammation, and blood-brain barrier (BBB) disruption, and significantly reduced intravascular fibrin and platelet deposition, and brain inflammatory cell infiltration in penumbra of I/R rats. Furthermore, a better beneficial trend was found in TNK bridging reperfusion at 0.5 hour after TNK compared with TNK bridging reperfusion at 1.0 hour after TNK.</p><p><strong>Conclusions: </strong>Our results demonstrate that intravenous TNK bridging reperfusion produced neuroprotective action through dissolving microvascular thrombus and alleviating inflammatory cell infiltration to improve microcirculation, with the result of maintaining BBB integrity and inhibiting neuroinflammation, and the neuroprotective benefit may be associated with the time from TNK to reperfusion.</p>","PeriodicalId":17326,"journal":{"name":"Journal of Thrombosis and Haemostasis","volume":" ","pages":""},"PeriodicalIF":5.5,"publicationDate":"2025-01-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143007528","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Multi-Gene Panel for Thrombophilia Testing in Venous Thromboembolism.","authors":"Andreas Verstraete, Mae Jeraldine De Vera, Christine Van Laer, Quentin Van Thillo, Sarissa Baert, Cyrielle Kint, Veerle Labarque, Chris Van Geet, Marc Jacquemin, Peter Verhamme, Kathleen Freson, Thomas Vanassche","doi":"10.1016/j.jtha.2024.12.041","DOIUrl":"https://doi.org/10.1016/j.jtha.2024.12.041","url":null,"abstract":"<p><strong>Background: </strong>Conventional tests for inherited thrombophilia focus on the five most-established inherited thrombophilias; i.e. deficiencies in antithrombin, protein C, and protein S, and the factor V Leiden and prothrombin G20210A variants. These tests identify thrombophilia in approximately 40% of tested patients with venous thromboembolism (VTE). Next-generation sequencing allows to detect variants in multiple coagulation-related genes, yet its clinical value for VTE remains unknown.</p><p><strong>Objectives: </strong>This study aims to report the findings from a multi-gene coagulation panel for VTE and assess its complementarity to conventional thrombophilia testing in clinical practice.</p><p><strong>Methodology: </strong>We conducted a single-center retrospective analysis of VTE patients tested with the Thrombosis-Hemostasis multi-gene (THG) panel, comprising 31 diagnostic-grade genes involved in thrombosis and hemostasis, from January 2019 to December 2023. We compared the results of the THG panel with conventional tests and analyzed characteristics associated with positive gene panel results.</p><p><strong>Results: </strong>The THG panel identified genetic variants in 63% of 194 VTE patients. Half of the variants were classified as (likely) pathogenic variants ((L)PV). Thirty-six (19%) cases carried variants in multiple genes. Among the 185 patients with available conventional test results, the THG panel detected non-compatible variants ((L)PV or variants of unknown significance (VUS)) in 76 patients (41%), which would remain undetected by performing conventional tests. Strictly concordant genetic findings were observed in 92 cases (50%).</p><p><strong>Conclusion: </strong>The use of the THG panel provides more insights into the underlying thrombophilia of patients with VTE; however, its implications for patient management require further investigation.</p>","PeriodicalId":17326,"journal":{"name":"Journal of Thrombosis and Haemostasis","volume":" ","pages":""},"PeriodicalIF":5.5,"publicationDate":"2025-01-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142971366","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"DESCRIPTION OF THE CLINICAL AND RADIOLOGICAL CHARACTERISTICS OF PULMONARY EMBOLISM IN COVID-19 VERSUS NON COVID-19 PATIENTS: A MULTICENTRIC CROSS-SECTIONAL STUDY OVER A 24-MONTH PERSPECTIVE.","authors":"Paola Sterpone, Marco Paolo Donadini, Irene Abatangelo, Laura Tofanelli, Asim Raza, Filippo Piacentino, Francesco Maria Vitale, Francesco Ricapito, Massimo Venturini, Walter Ageno, Francesco Pavesi, Eleonora Antonucci, Maurizio Cariati, Gian Marco Podda, Simone Birocchi","doi":"10.1016/j.jtha.2024.12.037","DOIUrl":"https://doi.org/10.1016/j.jtha.2024.12.037","url":null,"abstract":"<p><strong>Background: </strong>COVID-19 is associated with intense systemic inflammation and abnormal coagulation profile leading to an increased incidence of pulmonary embolism (PE). This study investigates whether PE in COVID-19 patients has different clinical, laboratory and radiological characteristics when compared to traditional PE in COVID negative patients.</p><p><strong>Methods: </strong>We conducted an observational, multicentric, cross-sectional study on consecutive patients diagnosed with PE at admission or during hospital stay from February 21^th 2019 to February 20^th 2021. We compared clinical and laboratory data and Computer Tomography (CT) images between COVID-19 positive and COVID-19 negative patients. The extent of PE was evaluated using the Qanadli Index.</p><p><strong>Results: </strong>Among 771 enrolled patients with acute PE, 89 were COVID-19 positive. COVID-19 patients were predominantly male (59.6% vs. 41.5%; p=0.001) and exhibited fewer classic VTE risk factors, such as previous VTE (3.5% vs. 11.5%; p=0.02) and active cancer (4.7% vs. 24.2%; p<0.0001). Additionally, these patients showed lower median Troponin-T and NT-proBNP levels (10 vs. 32 ng/L, p=0.0002; and 383 vs. 1448 pg/ml, p=0.004, respectively), a lower median Qanadli Index (4 vs. 7, p=0.0013), more distal PE obstructions (53.5% vs. 32.9%; p<0.001), and less frequent right ventricular dilatation (4.1% vs. 10.9%; p=0.09).</p><p><strong>Conclusion: </strong>In COVID-19 patients, traditional VTE risk factors were less frequent, a possible role for in situ thrombo-inflammatory processes. The reduced radiological extent and severity of PE observed in COVID-19 patients may riflect an in situ thrombo-inflammatory process rather than classical embolization; however, this hypotesis need to be confirmed by other studies.</p>","PeriodicalId":17326,"journal":{"name":"Journal of Thrombosis and Haemostasis","volume":" ","pages":""},"PeriodicalIF":5.5,"publicationDate":"2025-01-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142971433","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Tolerance to Factor VIII in the Era of Non-Factor Therapies: Immunological Perspectives and a Systematic Review of the Literature.","authors":"Lilianne Esmée van Stam, Sébastien Lacroix-Desmazes, Karin Fijnvandraat, Samantha Claudia Gouw","doi":"10.1016/j.jtha.2024.12.039","DOIUrl":"https://doi.org/10.1016/j.jtha.2024.12.039","url":null,"abstract":"<p><p>Persons with hemophilia A (PWHA) lack clotting factor VIII (FVIII) due to a genetic mutation in the F8 gene. The administration of FVIII concentrate leads to the development of neutralizing anti-FVIII antibodies (inhibitors) in about 30% of children with severe hemophilia A. The other 70% of children do not mount a detectable antibody response, suggesting that they may have developed tolerance towards FVIII. Our knowledge on the underlying immunological mechanisms that determine formation of inhibitors or apparent tolerance to FVIII is limited. Up to recently, FVIII concentrates were regularly used as prophylaxis. In the last years, Non-Factor Therapy (NFT) for prophylaxis is increasingly used, in which case FVIII concentrate administration is limited to treatment for bleeding or perioperative hemostasis. As NFT is very effective in the prevention of bleeds, patients may not be exposed to the deficient FVIII protein for periods up to a year or longer. Thus, while in the past persons with severe hemophilia were frequently exposed to the deficient antigen, exposure is now reduced to incidental treatment moments. It is currently not known how this will affect the tolerance for FVIII. In this review, we will discuss tolerance to FVIII from a clinical, immunological and epidemiological perspective. We aim to provide an outlook on the effect of reduced FVIII exposure on tolerance for FVIII in PWHA.</p>","PeriodicalId":17326,"journal":{"name":"Journal of Thrombosis and Haemostasis","volume":" ","pages":""},"PeriodicalIF":5.5,"publicationDate":"2025-01-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142971507","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Safety and efficacy of valoctocogene roxaparvovec with prophylactic glucocorticoids: 1-year results from the phase 3b, single-arm, open-label GENEr8-3 study.","authors":"Margareth C Ozelo, Jane Mason, Amy L Dunn, Paula Ribeiro Villaça, Ming-Ching Shen, Suresh Agarwal, Urooj Imtiaz, Hai Liu, Tara M Robinson","doi":"10.1016/j.jtha.2024.12.038","DOIUrl":"https://doi.org/10.1016/j.jtha.2024.12.038","url":null,"abstract":"<p><strong>Background: </strong>Valoctocogene roxaparvovec, an adeno-associated virus vector that transfers a human factor VIII (FVIII) coding sequence to hepatocytes, provides bleeding protection for people with severe hemophilia A (HA).</p><p><strong>Objective: </strong>Determine the efficacy and safety of valoctocogene roxaparvovec with concomitant prophylactic glucocorticoids in the open-label, single-arm, phase 3b GENEr8-3 trial.</p><p><strong>Methods: </strong>Participants with severe HA who were using HA prophylaxis received one 6x10¹³ vg/kg infusion of valoctocogene roxaparvovec concomitantly with daily prophylactic glucocorticoids (40 mg prednisolone equivalent/d weeks 0‒8; taper to 5 mg/d weeks 9‒19). The primary efficacy endpoint was change from baseline in FVIII activity (chromogenic substrate assay) at week 52. Secondary efficacy endpoints included annualized rate of FVIII use and annualized bleeding rate (ABR) for treated bleeds. Safety was assessed by adverse events (AEs). Analysis populations were intent-to-treat (ITT; received valoctocogene roxaparvovec) for safety analyses and modified ITT (mITT; ≥52 FVIII infusions in the year before dosing) for efficacy analyses.</p><p><strong>Results: </strong>Overall, 22 participants with severe HA received valoctocogene roxaparvovec. In the mITT population (n = 21), mean week 52 FVIII activity increased from baseline (imputed as 1 IU/dL) to 16.1 IU/dL (standard deviation [SD], 22.4; P = 0.0057); post-HA prophylaxis, mean treated ABR and mean annualized FVIII use decreased 67.1% and 91.6% from baseline, respectively (P <0.05). The most common AE was alanine aminotransferase elevation (20/22 participants). Glucocorticoid-related AEs occurred in 19/22 participants. No participants discontinued the study.</p><p><strong>Conclusions: </strong>Based on cross-trial comparisons, prophylactic glucocorticoids do not confer safety or efficacy benefits compared with reactive glucocorticoid regimens.</p>","PeriodicalId":17326,"journal":{"name":"Journal of Thrombosis and Haemostasis","volume":" ","pages":""},"PeriodicalIF":5.5,"publicationDate":"2025-01-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142971499","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Acute pulmonary embolism with and without hemodynamic instability (2003-2022): A Swiss nationwide epidemiological study.","authors":"Simon Wolf, Luca Valerio, Riccardo M Fumagalli, Stavros V Konstantinides, Silvia Ulrich, Frederikus A Klok, Suzanne C Cannegieter, Nils Kucher, Stefano Barco","doi":"10.1016/j.jtha.2024.12.040","DOIUrl":"https://doi.org/10.1016/j.jtha.2024.12.040","url":null,"abstract":"<p><strong>Background: </strong>Data on the epidemiological burden of acute pulmonary embolism (PE) in Switzerland is unavailable. Knowledge gaps remain on trends in PE-related comorbidities, PE severity, and length of in-hospital stay (LOS) at a nationwide level.</p><p><strong>Methods: </strong>We used nationwide, patient-level data including all patients aged 15 years or older hospitalized for PE in Switzerland from 2003 to 2022, amounting to N=180,600. Additionally, we analyzed the Swiss Death Registry for the same period. We estimated the disease-specific age-standardized incidence rates, mortality rates, in-hospital case fatality rates, proportional mortality rates, and LOS. Analyses were stratified by sex and the presence of features of high-risk PE.</p><p><strong>Findings: </strong>During the study period, the PE-related incidence rate increased from 0.87 (95%CI: 0.82;0.92) per 1,000 population in 2003 to 1.19 (95%CI: 1.15;1.24) in 2022. In contrast, a decreasing trend was found for mortality rates (18.7 [95%CI: 16.8;20.6] per 100,000 population in 2003, 13 [95%CI: 11.7;14.2] in 2022), in-hospital case fatality rate (9.8 [95%CI: 9.1;10.5] deaths per 100 hospitalized PE patients in 2003, 7.9 [95%CI: 7.4;8.5] in 2019, subsequent increase during COVID-19 pandemic), and LOS (11 [Q1-Q3: 7-18] days in 2003, 8 [Q1-Q3: 4-16] in 2022). No major sex-differences in trends were present. Except for LOS reduction, patients with high-risk features presented with similar trends.</p><p><strong>Conclusion: </strong>The incidence of acute PE in Switzerland increased over the last 20 years. Despite increasing trends in the median age at PE diagnosis, in-hospital case fatality and mortality rate decreased, particularly among patients with high-risk features, and the LOS progressively declined.</p>","PeriodicalId":17326,"journal":{"name":"Journal of Thrombosis and Haemostasis","volume":" ","pages":""},"PeriodicalIF":5.5,"publicationDate":"2025-01-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142971415","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Applying artificial intelligence to uncover the genetic landscape of coagulation factors.","authors":"Giulia Soldà, Rosanna Asselta","doi":"10.1016/j.jtha.2024.12.030","DOIUrl":"10.1016/j.jtha.2024.12.030","url":null,"abstract":"<p><p>Artificial intelligence (AI) is rapidly advancing our ability to identify and interpret genetic variants associated with coagulation factor deficiencies. This review introduces AI, with a specific focus on machine learning (ML) methods, and examines its applications in the field of coagulation genetics over the past decade. We observed a significant increase in AI-related publications, with a focus on hemophilia A and B. ML approaches have shown promise in predicting the functional impact of genetic variants and establishing genotype-phenotype correlations, exemplified by tools like \"Hema-Class\" for factor VIII variants. However, some challenges remain, including the need to expand variant selection beyond missense mutations (which is now the standard of most studies). For the future, the integration of AI in calling, detecting, and interpreting genetic variants can significantly improve our ability to process large-scale genomic data. In this frame, we discuss various AI/ML-based tools for genetic variant detection and interpretation, highlighting their strengths and limitations. As the field evolves, the synergistic application of multiple AI models, coupled with rigorous validation strategies, will be crucial in advancing our understanding of coagulation disorders and for personalizing treatment approaches.</p>","PeriodicalId":17326,"journal":{"name":"Journal of Thrombosis and Haemostasis","volume":" ","pages":""},"PeriodicalIF":5.5,"publicationDate":"2025-01-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142971419","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}