Journal of Thrombosis and Haemostasis最新文献

{"title":"Low VWF - unravelling an enigma wrapped in a conundrum.","authors":"James S O'Donnell,Ross I Baker,Ferdows Atiq","doi":"10.1016/j.jtha.2024.08.015","DOIUrl":"https://doi.org/10.1016/j.jtha.2024.08.015","url":null,"abstract":"The 2021 ASH ISTH NHF WFH guidelines recommendation that patients with VWF levels of 30-50 IU/dL and an increased bleeding phenotype be categorized as type 1 VWD rather than Low VWF has proved controversial. However, in support of that decision, recent data have demonstrated that individuals with partial quantitative VWF deficiency exhibit an age-dependent evolving phenotype and confirmed that Low VWF represents a sub-group within heterogeneous type 1 VWD. Nonetheless, type 1 VWD heterogeneity continues to pose significant diagnostic challenges. In this Forum Article, we address outstanding issues critical to preventing the inappropriate overdiagnosis of type 1 VWD, while maximizing access to healthcare and minimizing diagnostic delays. In addition, we propose an algorithm for type 1 VWD diagnosis. This algorithm pays special attention to individuals with plasma VWF levels in the 30-50 IU/dL range who have no or minimal bleeding history and have not yet been exposed to significant hemostatic challenges.","PeriodicalId":17326,"journal":{"name":"Journal of Thrombosis and Haemostasis","volume":null,"pages":null},"PeriodicalIF":10.4,"publicationDate":"2024-09-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142251215","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 changing face of cerebral venous sinus thrombosis - emerging new causes and treatments.","authors":"Caroline Dix,Beverley J Hunt","doi":"10.1016/j.jtha.2024.08.012","DOIUrl":"https://doi.org/10.1016/j.jtha.2024.08.012","url":null,"abstract":"Cerebral venous sinus thrombosis (CVST) is an uncommon site of venous thromboembolism. CVST more commonly affects younger people and women, in stark contrast to other forms of venous thrombosis where incidence increases with age and overall affects men. Traditional risk factors for the development of CVST include endogenous and exogenous estrogen (combined oral contraceptives and pregnancy and the puerperium), thrombophilias and rare haematologic disorders. New and emerging risk factors include obesity, polycystic ovary syndrome, COVID-19 infection, and vaccine-induced thrombocytopenia and thrombosis (VITT) and VITT-like disorders. Management centres around anticoagulation, managing the underlying cause, and consideration of invasive measures including endovascular thrombolysis and/or thrombectomy and craniectomy for severe cases. This review discusses the emerging risk factors and their identification, evidence for treatment including the use of direct oral anticoagulants, and the role of invasive management options.","PeriodicalId":17326,"journal":{"name":"Journal of Thrombosis and Haemostasis","volume":null,"pages":null},"PeriodicalIF":10.4,"publicationDate":"2024-09-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142182690","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":"Clinical validation and application of targeted long-range PCR and long-read sequencing-based analysis for haemophilia: experience from a haemophilia treatment centre in China.","authors":"Meizhen Shi,Yunting Ma,Xianwei Peng,Xu Zhou,Zifeng Cheng,Bobo Xie,Xianda Wei,Chunrong Gui,Aiping Mao,Wenting Lin,Jiefeng Luo,Yinghui Lai,Baoheng Gui","doi":"10.1016/j.jtha.2024.08.013","DOIUrl":"https://doi.org/10.1016/j.jtha.2024.08.013","url":null,"abstract":"BACKGROUNDTargeted long-read sequencing (LRS) is expected to comprehensively analyse diverse complex variants in haemophilia A (HA) and B (HB), caused by the F8 and F9 genes, respectively. However, its clinical applicability still requires extensive validation.OBJECTIVESTo evaluate the clinical applicability of targeted LRS-based analysis, compared with routine PCR-based methods.METHODSGene variants of retrieved subjects were retrospectively and prospectively analysed. Whole-genome sequencing (WGS) was performed to further analyse undiagnosed cases. Breakpoints of novel genomic rearrangements were mapped and validated using long-distance-PCR and long-range-PCR combined with sequencing.RESULTSTotally, 122 subjects were retrieved. In retrospective analysis of the 90 HA cases, HA-LRS assay showed consistent results in 84 cases compared with routine methods, and characterized six large deletions with their exact breakpoints confirmed by further validation in six cases (routine methods only presented failure in amplifying the involved exons). In prospective analysis of the 21 HA subjects, 20 variants of F8 were identified in 20 cases. For the remaining HA patient, no duplication/deletion or SNV/InDel was found, but a potential recombination involving exons 14 and 21 of F8 was observed by LRS. WGS analysis and further verification defined a 30,478bp tandem repeat involving exons 14-21 of F8. Among the 11 HB patients, HB-LRS analysis detected 11 SNVs/InDels in F9, consistent with routine methods.CONCLUSIONSTargeted LRS-based analysis is efficient and comprehensive to identify SNVs/InDels and genomic rearrangements of haemophilia genes, especially we first expanding the panel including F9. However, further investigation for complex gross rearrangement is still essential.","PeriodicalId":17326,"journal":{"name":"Journal of Thrombosis and Haemostasis","volume":null,"pages":null},"PeriodicalIF":10.4,"publicationDate":"2024-09-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142182689","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":"Factors Associated with Venous Thromboembolism Pharmacoprophylaxis Initiation in Hospitalized Medical Patients: The Medical Inpatients Thrombosis and Hemostasis (MITH) Study.","authors":"Allen B Repp,Andrew D Sparks,Katherine Wilkinson,Nicholas S Roetker,Jordan K Schaefer,Ang Li,Leslie A McClure,Deirdra R Terrell,Augusto Ferraris,Alys Adamski,Nicholas L Smith,Neil A Zakai","doi":"10.1016/j.jtha.2024.08.016","DOIUrl":"https://doi.org/10.1016/j.jtha.2024.08.016","url":null,"abstract":"BACKGROUNDAlthough guidelines recommend risk assessment for hospital-acquired venous thromboembolism (HA-VTE) to inform prophylaxis decisions, studies demonstrate inappropriate utilization of pharmacoprophylaxis in hospitalized medical patients. Predictors of pharmacoprophylaxis initiation in medical inpatients remain largely unknown.OBJECTIVETo determine factors associated with HA-VTE pharmacoprophylaxis initiation in adults hospitalized on medical services.DESIGNCohort study using electronic health record data from adult patients hospitalized on medical services at four academic medical centers between 2016 and 2019.PARTICIPANTSAmong 111,550 admissions not on intermediate or full-dose anticoagulation, 48,520 (43.5%) received HA-VTE pharmacoprophylaxis on the day of or the day after admission.MAIN MEASURESCandidate predictors of HA-VTE pharmacoprophylaxis initiation, including known HA-VTE risk factors, predicted HA-VTE risk, and bleeding diagnoses present on admission.KEY RESULTSAfter adjustment for age, sex, race/ethnicity, and study site, the strongest clinical predictors of HA-VTE pharmacoprophylaxis initiation were malnutrition and chronic obstructive pulmonary disease. Thrombocytopenia and history of gastrointestinal bleeding were associated with decreased odds of HA-VTE pharmacoprophylaxis initiation. Patients in the highest two tertiles of predicted HA-VTE risk were less likely to receive HA-VTE pharmacoprophylaxis than patients in the lowest (1st) tertile (OR 0.84, 95% CI [0.81, 0.86] for 2nd tertile, OR 0.95, 95% CI [0.92, 0.98] for 3rd tertile).CONCLUSIONSAmong patients not already receiving anticoagulants, HA-VTE pharmacoprophylaxis initiation during the first two hospital days was lower in patients with higher predicted HA-VTE risk and those with risk factors for bleeding. Reasons for not initiating pharmacoprophylaxis in those with higher predicted risk could not be assessed.","PeriodicalId":17326,"journal":{"name":"Journal of Thrombosis and Haemostasis","volume":null,"pages":null},"PeriodicalIF":10.4,"publicationDate":"2024-09-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142182688","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":"Endothelial colony-forming cells in the spotlight: insights into the pathophysiology of von Willebrand disease and rare bleeding disorders.","authors":"Sebastiaan N J Laan, Britte G Lenderink, Jeroen C J Eikenboom, Ruben Bierings","doi":"10.1016/j.jtha.2024.08.011","DOIUrl":"10.1016/j.jtha.2024.08.011","url":null,"abstract":"<p><p>Endothelial cells deliver a vital contribution to the maintenance of hemostasis by constituting an anatomical as well as functional barrier between the blood and the rest of the body. Apart from the physical barrier function, endothelial cells maintain the hemostatic equilibrium by their pro- and anticoagulant functions. An important part of their procoagulant contribution is the production of von Willebrand factor (VWF), which is a carrier protein for coagulation factor VIII and facilitates the formation of a platelet plug. Thus, VWF is indispensable for both primary and secondary hemostasis, which is exemplified by the bleeding disorder von Willebrand disease that results from qualitative or quantitative deficiencies in VWF. A cellular model that was found to accurately reflect the endothelium and its secretory organelles are endothelial colony-forming cells, which can be readily isolated from peripheral blood and constitute a robust ex vivo model to investigate the donor's endothelial cell function. This review summarizes some of the valuable insights on biology of VWF and pathogenic mechanisms of von Willebrand disease that have been made possible using studies with endothelial colony-forming cells derived from patients with bleeding disorders.</p>","PeriodicalId":17326,"journal":{"name":"Journal of Thrombosis and Haemostasis","volume":null,"pages":null},"PeriodicalIF":5.5,"publicationDate":"2024-09-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142145869","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":"Treatment of atrial fibrillation and venous thromboembolism with factor Xa inhibitors in severely obese patients.","authors":"Paul Dobry, Stephanie B Edwin, Brian Haymart, Geoffrey D Barnes, Scott Kaatz, Mona A Ali, Christopher Giuliano","doi":"10.1016/j.jtha.2024.08.009","DOIUrl":"10.1016/j.jtha.2024.08.009","url":null,"abstract":"<p><strong>Background: </strong>A paucity of data exists to support the use of factor (F)Xa inhibitors in severely obese patients with a weight of ≥150 kg or body mass index (BMI) of ≥50 kg/m².</p><p><strong>Objectives: </strong>The purpose of this study was to evaluate whether FXa inhibitors are as safe and effective as warfarin for the treatment of atrial fibrillation (AF) and/or venous thromboembolism (VTE) in individuals with a BMI of ≥50 kg/m² and/or weight of ≥150 kg.</p><p><strong>Methods: </strong>This was a multicenter retrospective cohort study of severely obese adult patients with AF and/or VTE treated with a FXa inhibitor or warfarin. The primary effectiveness outcome was composite odds of stroke, systemic embolism, or VTE; the primary safety outcome was odds of major bleeding. Secondary outcomes included incidence of stroke or systemic embolism, VTE, major bleeding, clinically relevant nonmajor bleeding, all-cause mortality, change in anticoagulation, and total number of hospital encounters. Outcomes were assessed for 12 months following initiation of study drug.</p><p><strong>Results: </strong>A total of 1736 patients were included. The mean weight and BMI of the overall cohort were 164.4 kg and 54.6 kg/m², respectively. There was no difference in odds of stroke, systemic embolism or VTE (odds ratio, 1.005; 95% CI, 0.6-1.68), or major bleeding (odds ratio, 0.9; 95% CI, 0.47-1.7) between groups.</p><p><strong>Conclusion: </strong>These data suggest that apixaban and rivaroxaban are safe and effective alternatives to warfarin for the treatment of AF and/or VTE in individuals with a BMI of ≥50 kg/m² and/or weight of ≥150 kg.</p>","PeriodicalId":17326,"journal":{"name":"Journal of Thrombosis and Haemostasis","volume":null,"pages":null},"PeriodicalIF":5.5,"publicationDate":"2024-09-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142145870","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":"Development of an assay using a modified coagulation factor V to measure protein S activity.","authors":"Keiko Maruyama, Koichi Kokame","doi":"10.1016/j.jtha.2024.08.010","DOIUrl":"10.1016/j.jtha.2024.08.010","url":null,"abstract":"<p><strong>Background: </strong>Protein S (PS) is an anticoagulant that functions as a cofactor for activated protein C and the tissue factor pathway inhibitor. PS deficiency is a risk factor for venous thromboembolism. PS activity is commonly measured using clot-based assays involving fibrin and thrombin production, but improvements are needed.</p><p><strong>Objectives: </strong>To develop a new assay for measuring plasma PS activity by quantifying the amount of activated coagulation factor (F)V cleaved by activated protein C.</p><p><strong>Methods: </strong>We designed a recombinant, modified FV (FVm) that mimicked FVa. We analyzed 160 purposively selected plasma samples from the Biobank of the National Cerebral and Cardiovascular Center.</p><p><strong>Results: </strong>The assay using mixed normal and PS-deficient plasma detected FVm cleavage in a PS concentration-dependent manner. The correlation between PS activity, measured using the FVm cleavage assay, and free PS antigen levels was relatively weak. We then sequenced all exons of PROS1 from 47 subjects with <60% activity in either the FVm cleavage assay or the clot-based assay. Nonsynonymous variants were identified in 12 of 24 subjects with <60% activity in both assays and in 2 of 7 subjects with <60% activity in the FVm cleavage assay alone. No variants were identified in 16 subjects with <60% activity in the clot-based assay alone. Unlike the clot-based assay, the FVm cleavage assay was not affected by the presence of rivaroxaban in the plasma.</p><p><strong>Conclusion: </strong>An assay using the FVm substrate may be less susceptible to interference and provide a more accurate evaluation of plasma PS activity than clot-based assays.</p>","PeriodicalId":17326,"journal":{"name":"Journal of Thrombosis and Haemostasis","volume":null,"pages":null},"PeriodicalIF":5.5,"publicationDate":"2024-09-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142145868","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":"Lack of factor VIII detection in humans and dogs with an intron 22 inversion challenges hypothesis regarding inhibitor risk.","authors":"Pooja Vir, Devi Gunasekera, Batsukh Dorjbal, Dennis McDaniel, Atul Agrawal, Elizabeth P Merricks, Margaret V Ragni, Cindy A Leissinger, Allen I Stering, Kenneth Lieuw, Timothy C Nichols, Kathleen P Pratt","doi":"10.1016/j.jtha.2024.08.007","DOIUrl":"10.1016/j.jtha.2024.08.007","url":null,"abstract":"<p><strong>Background: </strong>Almost half of severe hemophilia A (HA) cases are caused by an intron 22 inversion (Int22Inv) mutation, which truncates the 26-exon F8 messenger RNA (mRNA) after exon 22. Another F8 transcript, F8_B, is initiated from within F8-intron-22. F8_B mRNA consists of a short exon spliced to exons 23 to 26 and is expressed in multiple human cell types. It has been hypothesized that Int22Inv patients have self-tolerance to partial factor (F)VIII proteins expressed from these 2 transcripts. FVIII is expressed in endothelial cells, primarily in the liver and lungs. Several studies have reported FVIII expression in other cell types, although this has been controversial.</p><p><strong>Objectives: </strong>To determine if partial FVIII proteins are expressed from intron 22-inverted and/or F8_B mRNA and if FVIII is expressed in nonendothelial cells.</p><p><strong>Methods: </strong>A panel of FVIII-specific antibodies was validated and employed to label FVIII in cells and tissues and for immunoprecipitation followed by western blots and mass spectrometry proteomics analysis.</p><p><strong>Results: </strong>Immunofluorescent staining localized FVIII to endothelial cells in liver sections from non-HA but not HA-Int22Inv dogs. Neither FVIII nor FVIII_B was detected in human peripheral blood mononuclear cells, B cell or T cell lines, or cell lines expanded from peripheral blood mononuclear cells, whereas FVIII antigen and activity were readily detected in primary nonhemophilic liver sinusoidal endothelial cells.</p><p><strong>Conclusion: </strong>If FVIII is expressed in nonendothelial cells or if partial FVIII proteins are expressed in HA-Int22Inv, the concentrations are below the detection limits of these sensitive assays. Our results argue against promotion of immune tolerance through expression of partial FVIII proteins in Int-22Inv patients.</p>","PeriodicalId":17326,"journal":{"name":"Journal of Thrombosis and Haemostasis","volume":null,"pages":null},"PeriodicalIF":5.5,"publicationDate":"2024-09-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142133043","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 use of direct oral anticoagulants in the secondary prevention of venous thromboembolism in patients with severe thrombophilia: communication from the ISTH SSC Subcommittee on Physiological Anticoagulants and Thrombophilia","authors":"Mirjana Kovac ,&nbsp;Vera Ignjatovic ,&nbsp;Christelle Orlando ,&nbsp;Zsuzsanna Bereczky ,&nbsp;Beverley J. Hunt","doi":"10.1016/j.jtha.2024.08.006","DOIUrl":"10.1016/j.jtha.2024.08.006","url":null,"abstract":"<div><div>Direct oral anticoagulants (DOACs) are the first-line anticoagulants for the secondary prevention of venous thromboembolism (VTE). However, patients with severe inherited thrombophilias represent a group in whom the efficiency and safety of DOACs is poorly studied. In this communication, we focus on the utility of DOACs in the secondary prevention of VTE in patients with severe thrombophilia. Current evidence is based only on cohort or single-center studies, and poor data are available on compliance of the patients in the studies. Analysis of the studies suggested that full-dose DOACs and vitamin K antagonists have a similar efficacy and bleeding risk in the secondary prevention of VTE in patients with thrombophilia, with a low hazard ratio for recurrent VTE calculated from cohort studies for DOAC vs warfarin, ranging from 0.3 to 0.75. We wish to highlight that treatment failure is greater in those with severe forms of protein S deficiency (below 20%) and possibly in antithrombin deficiency type II heparin-binding site homozygous Budapest 3. In summary, the current approach to using DOACs in patients with severe thrombophilia is dependent on clinical judgment and experience. Limited evidence suggests that for those with severe thrombophilias, full-dose DOACs have similar utility as vitamin K antagonists. We recommend caution in using low-dose DOACs due to lack of evidence. Ideally, large randomized multicenter studies are required to develop a reliable treatment algorithm.</div></div>","PeriodicalId":17326,"journal":{"name":"Journal of Thrombosis and Haemostasis","volume":null,"pages":null},"PeriodicalIF":5.5,"publicationDate":"2024-09-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142133044","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":"Biomarker-enhanced cardiovascular risk prediction in patients with cancer: a prospective cohort study","authors":"Simon Kraler ,&nbsp;Luca Liberale ,&nbsp;Stephan Nopp ,&nbsp;Cornelia Englisch ,&nbsp;Ella Grilz ,&nbsp;Tetiana Lapikova-Bryhinska ,&nbsp;Alexander Akhmedov ,&nbsp;Federico Carbone ,&nbsp;Davide Ramoni ,&nbsp;Amedeo Tirandi ,&nbsp;Alessandro Scuricini ,&nbsp;Simone Isoppo ,&nbsp;Curzia Tortorella ,&nbsp;Federica La Rosa ,&nbsp;Cristina Michelauz ,&nbsp;Federica Frè ,&nbsp;Aurora Gavoci ,&nbsp;Anna Lisa ,&nbsp;Thomas M. Suter ,&nbsp;Arnold von Eckardstein ,&nbsp;Florian Moik","doi":"10.1016/j.jtha.2024.07.019","DOIUrl":"10.1016/j.jtha.2024.07.019","url":null,"abstract":"<div><h3>Background</h3><div>Continuously improving cancer-specific survival puts a growing proportion of cancer patients at risk of major adverse cardiovascular events (MACE), but tailored tools for cardiovascular risk prediction remain unavailable.</div></div><div><h3>Objectives</h3><div>To assess a broad panel of cardiovascular biomarkers and risk factors for the prediction of MACE and cardiovascular death in cancer patients.</div></div><div><h3>Methods</h3><div>In total, 2192 patients with newly diagnosed or recurrent cancer were followed prospectively for the occurrence of 2-year MACE and 5-year cardiovascular death. Univariable and multivariable risk models were fit to assess independent associations of cardiovascular risk factors and biomarkers with adverse outcomes, and a risk score was developed.</div></div><div><h3>Results</h3><div>Traditional cardiovascular risk factors and selected cancer types were linked to higher MACE risk. While levels of Lp(a), CRP, and GDF-15 did not associate with MACE, levels of ICAM-1, P-/E-/L-selectins, and NT-proBNP were independently linked to 2-year MACE risk. A clinical risk score was derived, assigning +1 point for male sex, smoking, and age of ≥60 years and +2 points for atherosclerotic disease, yielding a bootstrapped <em>C</em>-statistic of 0.76 (95% CI: 0.71-0.81) for the prediction of 2-year MACE. Implementation of biomarker data conferred improved performance (0.83, 95% CI: 0.78-0.88), with a simplified model showing similar performance (0.80, 95% CI: 0.74-0.86). The biomarker-enhanced and simplified prediction models achieved a <em>C</em>-statistic of 0.82 (95% CI: 0.71-0.93) and 0.74 (95% CI: 0.64-0.83) for the prediction of 5-year cardiovascular death.</div></div><div><h3>Conclusion</h3><div>Biomarker-enhanced risk prediction strategies allow the identification of cancer patients at high risk of MACE and cardiovascular death. While external validation studies are ongoing, this <em>first-of-its-kind</em> risk score may provide the basis for personalized cardiovascular risk assessment across cancer entities.</div></div>","PeriodicalId":17326,"journal":{"name":"Journal of Thrombosis and Haemostasis","volume":null,"pages":null},"PeriodicalIF":5.5,"publicationDate":"2024-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142120151","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}