Journal of Thrombosis and Haemostasis最新文献

{"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":"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 (F)VIII (FVIII) coding sequence to hepatocytes, provides bleeding protection for people with severe hemophilia A.</p><p><strong>Objectives: </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 hemophilia A who were using hemophilia A prophylaxis received one 6 × 10¹³ 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 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 (≥52 FVIII infusions in the year before dosing) for efficacy analyses.</p><p><strong>Results: </strong>Overall, 22 participants with severe hemophilia A received valoctocogene roxaparvovec. In the modified ITT population (n = 21), mean week 52 FVIII activity increased from baseline (imputed as 1 IU/dL) to 16.1 IU/dL (SD, 22.4; P = .0057); posthemophilia A prophylaxis, mean treated annualized bleeding rate and mean annualized FVIII use decreased 67.1% and 91.6% from baseline, respectively (P < .05). The most common AE was alanine aminotransferase elevation (20/22 participants). Glucocorticoid-related AEs occurred in 19 of 22 participants. No participants discontinued the study.</p><p><strong>Conclusion: </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 epidemiologic 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":"10.1016/j.jtha.2024.12.040","url":null,"abstract":"<p><strong>Background: </strong>Data on the epidemiologic burden of acute pulmonary embolism (PE) in Switzerland are 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>Objectives: </strong>To study the epidemiology of acute PE with a focus on overall trends, sex-stratified trends, and trends in patients with (vs without) hemodynamic instability.</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>Results: </strong>During the study period, the PE-related incidence rate increased from 0.87 (95% CI: 0.82, 0.92) per 1000 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 rates 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}

{"title":"A mutant complement factor H (W1183R) enhances proteolytic cleavage of von Willebrand factor by ADAMTS-13 under shear.","authors":"Wenjing Cao, Yi Liu, X Frank Zhang, X Long Zheng","doi":"10.1016/j.jtha.2024.11.031","DOIUrl":"10.1016/j.jtha.2024.11.031","url":null,"abstract":"<p><strong>Background: </strong>A loss-of-functional mutation (W1183R) in human complement factor H (CFH) is associated with complement-associated hemolytic uremic syndrome; mice carrying a similar mutation (W1206R) in CFH also develop thrombotic microangiopathy but its plasma von Willebrand factor (VWF) multimer sizes were dramatically reduced. The mechanism underlying such a dramatic change in plasma VWF multimer distribution in these mice is not fully understood.</p><p><strong>Objectives: </strong>To determine the VWF and CFH interaction and how CFH proteins affect VWF multimer distribution.</p><p><strong>Methods: </strong>We employed recombinant protein expression, purification, and various biochemical and biophysical tools.</p><p><strong>Results: </strong>Purified recombinant W1183R-CFH but not wild-type (WT) CFH protein enhanced the proteolytic cleavage of both peptidyl and multimeric VWF substrates by recombinant ADAMTS-13 in a concentration-dependent manner. Microscale thermophoresis assay demonstrated that both W1183R-CFH and WT-CFH proteins bound various VWF fragments (eg, AIM-A1, A1-A2-A3, D'D3, D'D3-A1, and D'D3-A1-A2) with high affinities. Optical tweezer experiments further showed a concentration-dependent alteration in the contour length (L_c) and the persistent length (L_p) following pulling VWF-A2 domain in the presence of W1183R-CFH or WT-CFH protein. AlphaFold experiments revealed conformational changes in the VWF-A2, particularly the central region where the cleavage bond resides following addition of W1183R-CFH or WT-CFH protein.</p><p><strong>Conclusion: </strong>These results demonstrate for the first time that W1183R-CFH but not WT-CFH protein enhances the proteolytic cleavage of VWF by ADAMTS-13 under shear. This may be achieved by mechanic-induced conformational changes of the central A2 domain, leading to an enhanced cleavage of Tyr¹⁶⁰⁵-Met¹⁶⁰⁶ bond by ADAMTS-13 under pathophysiological conditions.</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":"142971360","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":"Mice with reduced protease-activated receptor 4 reactivity show decreased venous thrombosis and platelet procoagulant activity.","authors":"Elizabeth A Knauss, Johana Guci, Norman Luc, Dante Disharoon, Grace H Huang, Anirban Sen Gupta, Marvin T Nieman","doi":"10.1016/j.jtha.2024.12.031","DOIUrl":"10.1016/j.jtha.2024.12.031","url":null,"abstract":"<p><strong>Background: </strong>Hypercoagulation and thrombin generation are major risk factors for venous thrombosis. Sustained thrombin signaling through protease-activated receptor (PAR) 4 promotes platelet activation, phosphatidylserine exposure, and subsequent thrombin generation. A single nucleotide polymorphism in PAR4 (rs2227376) changes proline to leucine extracellular loop 3, which decreases PAR4 reactivity and is associated with a lower risk for venous thromboembolism (VTE) in a genome wide association studies meta-analysis.</p><p><strong>Objectives: </strong>The goal of this study was to determine the mechanism for the association of rs2227376 with a reduced risk of VTE using mice with a homologous mutation (PAR4-P322L).</p><p><strong>Methods: </strong>Venous thrombosis was examined using our recently generated PAR4-P322L mice in the inferior vena cava stasis and stenosis models. Coagulation and clot stability were measured using rotational thromboelastometry. Thrombin-generating potential was measured in platelet-rich plasma. Phosphatidylserine surface expression and platelet-neutrophil aggregates were analyzed using flow cytometry.</p><p><strong>Results: </strong>Mice heterozygous (PAR4^P/L) or homozygous (PAR4^L/L) at position 310 had reduced sizes of venous clots at 48 hours. PAR4^P/L and PAR4^L/L platelets had progressively decreased phosphatidylserine in response to thrombin and convulxin, in addition to decreased thrombin generation and decreased PAR4-mediated platelet-neutrophil aggregation.</p><p><strong>Conclusion: </strong>The leucine allele in extracellular loop 3, PAR4-322L, leads to fewer procoagulant platelets, decreased endogenous thrombin potential, and reduced platelet-neutrophil aggregation. This decreased ability to generate thrombin and bind to neutrophils offers a mechanism for PAR4's role in VTE, highlighting a key role for PAR4 signaling.</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":"142971363","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":"Peak and trough concentrations of apixaban and rivaroxaban in adult patients: a systematic review and meta-analysis.","authors":"Christian Andrew Almalbis, Adyani Md Redzuan, Chester Paul Andrada, Nicole Ann Gonzaga, Shamin Mohd Saffian","doi":"10.1016/j.jtha.2024.12.032","DOIUrl":"10.1016/j.jtha.2024.12.032","url":null,"abstract":"<p><strong>Background: </strong>Apixaban and rivaroxaban are activated factor X (FXa) inhibitors commonly used for treatment of venous thromboembolism and stroke prevention in patients with atrial fibrillation. While routine monitoring of their concentrations is not recommended, but it may be beneficial in certain situations. Expected peak and trough concentrations remain poorly understood, with most data derived from small studies.</p><p><strong>Objectives: </strong>To establish the average peak and trough concentrations of apixaban and rivaroxaban from real-world studies.</p><p><strong>Methods: </strong>PubMed, Scopus, and Web of Science were searched until October 2023 for observational studies reporting apixaban and rivaroxaban concentrations. Meta-regression was used to examine factors influencing these concentrations.</p><p><strong>Results: </strong>Sixteen studies involving 1054 apixaban and 1321 rivaroxaban patients were pooled using random-effects model. Mean apixaban peak concentrations were 157 ng/mL (95% CI, 127-187) for 2.5 mg and 228 ng/mL (95% CI, 204-252) for 5 mg, with trough concentrations of 77 ng/mL (95% CI, 56-98) and 113 ng/mL (95% CI, 101-124), respectively. Mean rivaroxaban peak concentrations were 168 ng/mL (95% CI, 104-232) for 10 mg, 225 ng/mL (95% CI, 192-257) for 15 mg, and 229 ng/mL (95% CI, 193-264) for 20 mg, with trough concentrations of 23 ng/mL (95% CI, 13-32), 31 ng/mL (95% CI, 26-36), and 36 ng/mL (95% CI, 25-47), respectively. Meta-regression revealed age and creatinine clearance correlated with apixaban peak concentrations. Creatinine clearance correlated with apixaban and rivaroxaban trough concentrations.</p><p><strong>Conclusion: </strong>The pooled mean concentrations align with expected concentration ranges reported in different pharmacokinetic studies.</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":"142971441","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":"Accurate evaluation of factor VIII activity of efanesoctocog alfa in the presence of emicizumab.","authors":"Christophe Nougier, Steven W Pipe, Ingrid Pabinger, Claire Pouplard, Roger E G Schutgens, Cedric Hermans, Guy Young, Edison Sexton, Peter Quehenberger, Eve-Anne Guery, Albert Huisman, Marie-Astrid Van Dievoet, Elizabeth Marquez, Yesim Dargaud","doi":"10.1016/j.jtha.2024.12.034","DOIUrl":"10.1016/j.jtha.2024.12.034","url":null,"abstract":"<p><strong>Background: </strong>Efanesoctocog is a B-domain-deleted, Fc-fusion factor (F)VIII linked to the D'D3 domain of von Willebrand factor and 2 XTEN polypeptides, designed for an ultra-extended half-life for prophylaxis in hemophilia A, but also aiding in managing acute bleeding or surgery in patients on long-term emicizumab. However, no current laboratory method accurately measures FVIII levels in the presence of emicizumab.</p><p><strong>Objectives: </strong>To test whether the bovine chromogenic FVIII assay, specifically calibrated for efanesoctocog, could provide an accurate assessment of efanesoctocog activity.</p><p><strong>Methods: </strong>Seven centers across 5 countries received 12 plasma samples to measure in triplicate using 2 calibration methods across 3 independent days. Samples (n = 6) contained either only efanesoctocog (FVIII activity [FVIII:C]= 5 to 150 IU/dL), or efanesoctocog (FVIII:C = 5 to 150 IU/dL) in combination with emicizumab (50 μg/mL; n = 5). One sample contained efanesoctocog (FVIII:C = 50 IU/dL) and a high dose of emicizumab (80 μg/mL); another sample contained efanesoctocog (FVIII:C = 50 IU/dL) with a low dose of emicizumab (20 μg/mL). Each center used its own analyzers, along with their usual reagents.</p><p><strong>Results: </strong>Chromogenic assay (CSA) calibrated with standard calibrators highly overestimates FVIII:C. However, specific calibration with efanesoctocog enabled accurate measurement of FVIII:C, with low inter- and intra-laboratory variability, and no interference from emicizumab. All CSA reagents used in the study demonstrated low variability across different laboratories (interlaboratory coefficient of variation ranges between 9% and 20%).</p><p><strong>Conclusion: </strong>Specific calibration of the FVIII CSA using efanesoctocog and bovine reagents allows for accurate measurement of FVIII:C in patients receiving efanesoctocog, even in the presence of emicizumab.</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":"142971411","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":"Systematic analysis of the design, methodology, and patient population characteristics of the pediatric direct oral anticoagulant trials of venous thromboembolism treatment.","authors":"Marisol Betensky, Manuela Albisetti, Tina Biss, Rukhmi V Bhat, Leonardo R Brandão, Thomas Diacovo, Paul Monagle, Leslie Raffini, Shoshana Revel-Vilk, C Heleen van Ommen, Hilary Whitworth, Neil A Goldenberg, Christoph Male","doi":"10.1016/j.jtha.2024.12.035","DOIUrl":"10.1016/j.jtha.2024.12.035","url":null,"abstract":"<p><strong>Background: </strong>The pediatric direct oral anticoagulation (DOAC) trials provide an opportunity to evaluate and characterize challenges in their design and execution to inform future antithrombotic trials.</p><p><strong>Objectives: </strong>To perform a systematic review of pediatric DOAC trials for the treatment of venous thromboembolism to critically appraise their methodology and understand the feasibility and challenges.</p><p><strong>Methods: </strong>We performed a systematic search of MEDLINE, EMBASE, the Cochrane Library, and ClinicalTrials.gov (January 2002 to December 2022). Studies reporting the results of interventional trials of a DOAC for the treatment of acute venous thromboembolism in children and their respective design papers were included. Trial registration information was reviewed in ClinicalTrials.gov. Discrepancies in study design, targeted populations, sample size, and analyses between planned and actual trial conduct were examined qualitatively.</p><p><strong>Results: </strong>Five published studies and unpublished data for 2 additional trials were included. All trials had modifications to their design or methodology and discrepancies between the trial's registration and the final published study, suggesting feasibility challenges. Modifications to the eligibility criteria, changes in sample size, challenges with the recruitment of younger patients, and an enrolled population not matching the clinical target population were identified for all trials. Discrepancies in outcome reporting, particularly for secondary endpoints, were also common.</p><p><strong>Conclusion: </strong>DOAC trials experienced feasibility challenges that led to design or methodology modifications. Future pediatric antithrombotic trials will need to be adaptive in their design, prioritize enrollment of younger children and input from clinicians providing care to target populations, ensure that enrolled populations match the clinical population, and select clinically meaningful endpoints.</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":"142971503","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}