Journal of Thrombosis and Haemostasis最新文献

{"title":"An update on laboratory detection and interpretation of antiphospholipid antibodies for diagnosis of antiphospholipid syndrome: guidance from the ISTH-SSC Subcommittee on Lupus Anticoagulant/Antiphospholipid Antibodies","authors":"Katrien M.J. Devreese ,&nbsp;Maria Laura Bertolaccini ,&nbsp;D. Ware Branch ,&nbsp;Bas de Laat ,&nbsp;Doruk Erkan ,&nbsp;Emmanuel J. Favaloro ,&nbsp;Vittorio Pengo ,&nbsp;Thomas L. Ortel ,&nbsp;Denis Wahl ,&nbsp;Hannah Cohen","doi":"10.1016/j.jtha.2024.10.022","DOIUrl":"10.1016/j.jtha.2024.10.022","url":null,"abstract":"<div><div>Antiphospholipid syndrome (APS) diagnosis is dependent on the accurate detection and interpretation of antiphospholipid antibodies (aPL). Lupus anticoagulant (LA), anticardiolipin antibodies (aCL), and anti-beta2 glycoprotein I antibodies (aβ2GPI) remain the cornerstone of the laboratory part of APS diagnosis. In the 2023 American College of Rheumatology (ACR)/European Alliance of Associations for Rheumatology (EULAR) APS classification criteria, the type of laboratory parameters remain essentially unchanged compared with the updated Sapporo classification criteria, and aCL and aβ2GPI measurement are still restricted to enzyme-linked immunosorbent assays (ELISAs) with moderate and high titer aPL thresholds defined as 40 and 80 Units, respectively, and a cutoff calculated by the 99th percentile has been abandoned. We must differentiate between classification criteria and assessment of aPL in clinical care. Classification criteria are strict and meant for participant inclusion in studies and trials to study homogeneous populations of patients. In contrast, laboratory detection for APS diagnosis in daily practice is broader, meant to diagnose each APS patient to optimize their management. Nowadays, there is increasing use of measurement of aPL by methods other than ELISAs , the semiquantitative reporting of titers is a matter of debate, as well as the role of the isotypes immunoglobulin (Ig)M and IgA, and the role of other aPL, such as antiphosphatidylserine (aPS)/prothrombin (PT) antibodies. Patients diagnosed with the disease may or may not fulfill the classification criteria, and inappropriate use of classification criteria may lead to mis(under)diagnosis. The aim of this guidance, based on literature and expert opinion, is to provide guidance recommendations for laboratory workers and clinicians on routine diagnostic assessment of patients with suspected APS.</div></div>","PeriodicalId":17326,"journal":{"name":"Journal of Thrombosis and Haemostasis","volume":"23 2","pages":"Pages 731-744"},"PeriodicalIF":5.5,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142605177","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":"The dynamic range of immunoassays for heparin-induced thrombocytopenia","authors":"Henning Nilius ,&nbsp;Samra Naas ,&nbsp;Jan-Dirk Studt ,&nbsp;Dimitrios A. Tsakiris ,&nbsp;Andreas Greinacher ,&nbsp;Adriana Mendez ,&nbsp;Adrian Schmidt ,&nbsp;Walter A. Wuillemin ,&nbsp;Bernhard Gerber ,&nbsp;Prakash Vishnu ,&nbsp;Lukas Graf ,&nbsp;Johanna A. Kremer Hovinga ,&nbsp;Tamam Bakchoul ,&nbsp;Christos Nakas ,&nbsp;Michael Nagler","doi":"10.1016/j.jtha.2024.10.026","DOIUrl":"10.1016/j.jtha.2024.10.026","url":null,"abstract":"<div><h3>Background</h3><div>Following the current guidelines, immunoassays for the diagnosis of heparin-induced thrombocytopenia (HIT) are interpreted dichotomously, with test results categorized as either positive or negative. However, the extent to which test results hold diagnostic significance across the entire dynamic range remains unclear.</div></div><div><h3>Objectives</h3><div>We utilized data from the prospective towards precise and rapid diagnosis of heparin-induced thrombocytopenia study, comprising 1393 consecutive patients with suspected HIT, to assess the diagnostic significance of 2 heparin/platelet factor 4 immunoassay test results across their respective dynamic ranges: HemoSil Acustar HIT IgG (chemiluminescence immunoassay [CLIA]) and Lifecodes PF4 immunoglobulin G (enzyme-linked immunosorbent assay [ELISA]).</div></div><div><h3>Methods</h3><div>HIT diagnosis was determined by a washed platelet heparin-induced platelet activation assay. For each measurement point in the dataset, we computed likelihood ratios (LRs), sensitivities, and specificities. To provide posttest probabilities for individual test results, we calculated interval-specific LRs and integrated them into a web-based calculator.</div></div><div><h3>Results</h3><div>The prevalence of HIT was 8.5% (<em>n</em> = 119). An LR of ≥10 was first achieved at 0.3% of the dynamic range (0.4 U/mL; CLIA) and then at 16% (0.64 optical density; ELISA). An LR of ≥100 was present at 9.4% (12 U/mL; CLIA) and 75.0% (3.0 optical density; ELISA). The slope of the linear regression line (LR ∼ dynamic range) was 9.5 (CLIA) and 0.9 (ELISA).</div></div><div><h3>Conclusion</h3><div>Despite both immunoassays showing an association between results and diagnostic significance, the strength of the association varies by assay. CLIA has a larger increase per measurement unit. Posttest probabilities for individual patients can be estimated using a web-based calculator: <span><span>https://pcd-research.shinyapps.io/BayesianCalculator/</span><svg><path></path></svg></span>.</div></div>","PeriodicalId":17326,"journal":{"name":"Journal of Thrombosis and Haemostasis","volume":"23 2","pages":"Pages 684-691"},"PeriodicalIF":5.5,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142622792","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"“Thromboplastin calibration revisited to look for possible revision of the World Health Organization recommendations”: comment from Kitchen et al.","authors":"Matthew Kitchen,&nbsp;Michelle Bryant,&nbsp;Paula Brown,&nbsp;Anita Woolley,&nbsp;Steve Kitchen","doi":"10.1016/j.jtha.2024.10.031","DOIUrl":"10.1016/j.jtha.2024.10.031","url":null,"abstract":"","PeriodicalId":17326,"journal":{"name":"Journal of Thrombosis and Haemostasis","volume":"23 2","pages":"Pages 750-752"},"PeriodicalIF":5.5,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143074749","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":"Frailty and Risk of Venous Thromboembolism in Older Adults: The Atherosclerosis Risk in Communities (ARIC) Study.","authors":"Tobyn S Chiu, James S Pankow, Mary Cushman, B Gwen Windham, Kunihiro Matsushita, Yejin Mok, Anna M Kucharska-Newton, Weihong Tang, Pamela L Lutsey","doi":"10.1016/j.jtha.2025.01.006","DOIUrl":"https://doi.org/10.1016/j.jtha.2025.01.006","url":null,"abstract":"<p><strong>Background: </strong>Frailty may be a marker of risk for developing venous thromboembolism (VTE).</p><p><strong>Objective: </strong>To examine the relationship of frailty and its components with risk of incident VTE among older adults.</p><p><strong>Methods: </strong>We examined 5,551 participants of the Atherosclerosis Risk in Communities Study without a history of VTE, using visit 5 (2011-2013) as baseline (mean age 75.4, 57.8% female, 21.5% Black race). Frailty status (frail, prefrail, or robust) was defined as having >3 components, 1-2 components, or no components, respectively, among assessments of weight loss, low grip strength, exhaustion, slow walking speed, and low physical activity. VTE events were identified from hospitalization records and adjudicated by physicians.</p><p><strong>Results: </strong>182 incident VTE events accrued over a median follow-up of 7.2 years. Participants who were frail, versus robust, had a hazard ratio (HR) for incident VTE of 2.20 (95% CI: 1.30-3.71) after accounting for demographics. Further adjustment for potential confounders only slightly attenuated the association [2.09 (1.23-3.55)]. When analyzed separately, frailty was associated with a fully-adjusted HR of 2.46 (1.26-4.80) for provoked VTE and 1.56 (0.66-3.69) for unprovoked VTE. Of the frailty components, exhaustion, slow walking speed, and low physical activity were significantly associated with increased risk of incident VTE.</p><p><strong>Conclusions: </strong>Among this sample of older adults, frail participants had a 2-fold greater risk of incident VTE than robust participants. Exhaustion, slow walking speed, and low physical activity were frailty components identified as being predictors of incident VTE. Frailty status may be a means for identifying older adults at elevated VTE risk.</p>","PeriodicalId":17326,"journal":{"name":"Journal of Thrombosis and Haemostasis","volume":" ","pages":""},"PeriodicalIF":5.5,"publicationDate":"2025-01-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143080581","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":"THE INDIVIDUAL FIBRINOLYTIC CAPACITY PREDICTS EFFICACY OF ULTRASOUND-ASSISTED CATHETER-DIRECTED THROMBOLYSIS IN PATIENTS WITH ACUTE PULMONARY EMBOLISM.","authors":"Dominik F Draxler, Justine Brodard, Heidi Ho, Konstantina Chalkou, Elisabeth Turovskij, Charithani B Keragala, Thomas Lillicrap, Dierik Heg, Johanna A Kremer Hovinga, Stephan Windecker, Robert L Medcalf, Anne Angelillo-Scherrer, Stefan Stortecky","doi":"10.1016/j.jtha.2024.12.043","DOIUrl":"https://doi.org/10.1016/j.jtha.2024.12.043","url":null,"abstract":"<p><strong>Background: </strong>Ultrasound-assisted catheter-directed thrombolysis (USAT) is nowadays available as an alternative reperfusion approach for acute pulmonary embolism (PE). The lytic agent recombinant tissue-type plasminogen activator (rt-PA) activates the effector protease plasmin to induce fibrinolysis. The aim of this study was to identify predictive markers for the efficacy of USAT in patients with acute PE.</p><p><strong>Patients/methods: </strong>In a single-center cohort study of USAT for intermediate-high or high-risk PE, pulmonary-arterial hemodynamic measurements were performed, and plasma samples obtained from 35 patients before treatment start, at 6 hours (during infusion of rt-PA), as well as at 24 hours after treatment start (post-lysis). The hemostatic properties were evaluated with thromboelastometry, assessment of fibrinolytic markers, and the ex vivo capacity of rt-PA-spiked plasma to generate the plasmin-antiplasmin (plap) complex.</p><p><strong>Results: </strong>Patients presented with an elevated mean pulmonary artery pressure (PAPm; 32.9 ± 7.6 mmHg), with a post-lysis reduction of 9.4 ± 8.3 mmHg on average, yet the treatment response varied markedly across individuals. The endogenous fibrinolytic capacity, as represented by plap complex and D-dimer levels as well as consumption of the endogenous fibrinolysis inhibitor α2-antiplasmin at 6 hours predicted the individual treatment efficacy, indicated by the reduction in PAPm (all p<0.05). Furthermore, ex vivo assessment of the fibrinolytic potential before start of USAT also predicted efficacy. Both, ML INTEM, as well as the novel parameter fibrin-sensitivity ratio were identified as predictors for USAT responsiveness (both p<0.05).</p><p><strong>Conclusions: </strong>Markers of fibrinolysis may be harnessed to predict treatment responsiveness to USAT in acute PE patients.</p>","PeriodicalId":17326,"journal":{"name":"Journal of Thrombosis and Haemostasis","volume":" ","pages":""},"PeriodicalIF":5.5,"publicationDate":"2025-01-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143066719","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":"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":"Multigene 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":"10.1016/j.jtha.2024.12.041","url":null,"abstract":"<p><strong>Background: </strong>Conventional tests for inherited thrombophilia focus on the 5 most-established inherited thrombophilias; ie 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 aimed to report the findings from a multigene coagulation panel for VTE and assess its complementarity to conventional thrombophilia testing in clinical practice.</p><p><strong>Methods: </strong>We conducted a single-center retrospective analysis of VTE patients tested with the Thrombosis-Hemostasis multigene (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)PVs). Thirty-six (19%) cases carried variants in multiple genes. Among the 185 patients with available conventional test results, the THG panel detected noncompatible variants ([L]PVs or variants of unknown significance) 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}