Research and Practice in Thrombosis and Haemostasis最新文献

{"title":"Quantifying endothelial damage by digital droplet polymerase chain reaction (PCR) of endothelial cell-free DNA in COVID-19 patients","authors":"Tiphaine Ruggeri ,&nbsp;Gertrud Wiedemann ,&nbsp;Noëlia Schärz ,&nbsp;Barbara Hügli ,&nbsp;Andreas Limacher ,&nbsp;Cédric Hirzel ,&nbsp;Naomi Porret ,&nbsp;Sacha Zeerleder","doi":"10.1016/j.rpth.2025.103320","DOIUrl":"10.1016/j.rpth.2025.103320","url":null,"abstract":"<div><h3>Background</h3><div>COVID-19, caused by SARS-CoV-2, triggers severe systemic inflammation and multiple organ dysfunction. Microvascular complications, potentially arising from endothelial cell infection and/or immunothrombosis, play a central role in the disease's pathophysiology. Upon cell activation and/or cell death, cells release cell-free DNA (cfDNA) into the circulation, and cfDNA derived specifically from endothelial cells may serve as a marker of microvascular damage severity.</div></div><div><h3>Objectives</h3><div>In this study, we aimed to develop an assay to specifically measure endothelial cell-derived DNA as a marker of microvascular damage in COVID-19 patients.</div></div><div><h3>Methods</h3><div>In this study, we developed a methylation-specific digital droplet polymerase chain reaction assay targeting the promoter of the <em>NOS3</em> gene to quantify circulating endothelial cell-derived cfDNA in COVID-19 patients followed longitudinally at inclusion, day 11, and day 28.</div></div><div><h3>Results</h3><div>Total cfDNA and endothelial-specific cfDNA levels significantly increased with COVID-19 disease severity, with the highest levels in patients with severe COVID-19. Notably, patients with mild COVID-19 showed endothelial cfDNA levels comparable to those of healthy controls, and levels remained stable from inclusion through day 28. In contrast, patients with moderate disease severity showed significantly elevated endothelial cfDNA levels compared with controls, which declined over time. Patients with severe COVID-19 displayed persistently high endothelial cfDNA levels throughout the observation period.</div></div><div><h3>Conclusion</h3><div>Using a digital droplet polymerase chain reaction assay specific for cfDNA from endothelial cells, we demonstrated endothelial cell damage in patients with COVID-19 that correlated with disease severity.</div></div>","PeriodicalId":20893,"journal":{"name":"Research and Practice in Thrombosis and Haemostasis","volume":"10 1","pages":"Article 103320"},"PeriodicalIF":3.4,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147277017","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Beyond a century of discovery: the global and persistent burden of underdiagnosis in von Willebrand disease","authors":"Omid Seidizadeh ,&nbsp;Rezan Abdul-Kadir ,&nbsp;Pier Mannuccio Mannucci ,&nbsp;Flora Peyvandi","doi":"10.1016/j.rpth.2026.103359","DOIUrl":"10.1016/j.rpth.2026.103359","url":null,"abstract":"<div><div>In February 2026, von Willebrand disease (VWD) will mark a century since its first description by Dr Erik Adolf von Willebrand. VWD is the most common inherited bleeding disorder and characterized predominantly by mucocutaneous bleeding. Despite remarkable advances in understanding its biology, diagnostic assays, genetics, and treatment, VWD remains widely underdiagnosed and misdiagnosed. Population-based studies estimate a prevalence between 0.8% and 1.6%, with 1 in 1000 individuals carry clinically significant VWD phenotypes, but global registry-reported prevalence averages only 25.6 per million, highlighting a striking gap between expected and identified cases. Underdiagnosis is driven by low awareness among health care providers, clinical and laboratory heterogeneity, assay variability, limited access to specialized testing, and misclassification as other bleeding disorders. Although VWD affects both sexes equally, women and girls are disproportionately impacted, with up to 90% experiencing heavy menstrual bleeding, 30% to 50% facing postpartum hemorrhage, and many missing school or workdays due to bleeding. Median diagnostic delay in women can exceed 14 years, often with multiple severe bleeding episodes prior to recognition. Disparities are particularly pronounced in low- and middle-income countries, where only severe cases are typically identified. Addressing these gaps requires global harmonization of diagnostic standards, increased awareness among health care providers, broader use of bleeding assessment tools, expanded laboratory capacity, and integration of sex-specific and precision medicine approaches. Coordinated policy, education, and awareness initiatives are essential to ensure early detection, equitable care, and optimal outcomes. The goal for the second century of VWD is that all patients are accurately diagnosed and appropriately treated.</div></div>","PeriodicalId":20893,"journal":{"name":"Research and Practice in Thrombosis and Haemostasis","volume":"10 1","pages":"Article 103359"},"PeriodicalIF":3.4,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147276639","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The Thromboembolism Heparinization and AntithrombiN Observational Study (THANOS-1)","authors":"Christiana K. Prucnal ,&nbsp;Grace Wang ,&nbsp;Weixing Huang ,&nbsp;Nora Horick ,&nbsp;Ryan Mize ,&nbsp;Isabel Dhar ,&nbsp;Tyleah Brown ,&nbsp;Sophie Flomenbaum ,&nbsp;Kyle E. Chang ,&nbsp;Timothy M. Matthews ,&nbsp;Gregory A. Peters ,&nbsp;Drew A. Birrenkott ,&nbsp;Karsten Stannek ,&nbsp;Eddie Eun Sang Lee ,&nbsp;Sacha Uljon ,&nbsp;Christopher Kabrhel","doi":"10.1016/j.rpth.2026.103367","DOIUrl":"10.1016/j.rpth.2026.103367","url":null,"abstract":"<div><h3>Background</h3><div>Acute pulmonary embolism (PE) affects both hemodynamics and the clotting system, and changes in clotting protein activity may affect the effectiveness of anticoagulation. For example, PE may represent an acute, acquired antithrombin (AT)-deficient state, which may limit heparin effectiveness. However, the incidence and clinical effects of acquired AT deficiency after PE are not known.</div></div><div><h3>Objectives</h3><div>Our primary aim was to calculate the proportion of patients with PE and acquired AT deficiency, defined a priori as &lt;80% functional activity. We also analyzed &lt;90%, &lt;100%, and &lt;110% AT activity. Secondary aims were to identify clinical factors and outcomes associated with acquired AT deficiency.</div></div><div><h3>Methods</h3><div>We performed a prospective, observational study of patients diagnosed with acute PE without contraindications to heparin anticoagulation. We obtained blood within 24 hours after positive PE imaging and measured AT activity. Outcomes were culled from the medical record.</div></div><div><h3>Results</h3><div>We analyzed 200 patients. Mean age was 62 ± 16 years, and 120 (60%) were men. Fifty-four (27%) patients had &lt;80%, 111 (56%) &lt;90%, and 159 (80%) &lt;100% AT activity. Low AT activity (&lt;80%) was associated with longer hospital length of stay (<em>P</em> &lt; .0001), intensive care unit admission (<em>P</em> = .0085), and adverse clinical outcomes (<em>P</em> = .0042), but not subtherapeutic anticoagulation.</div></div><div><h3>Conclusion</h3><div>Acquired AT deficiency is common after acute PE, occurring in at least one-quarter of all patients. Low AT levels are associated with adverse clinical outcomes, intensive care unit admission, and longer hospital length of stay, but whether this is related to subtherapeutic anticoagulation is not clear.</div></div>","PeriodicalId":20893,"journal":{"name":"Research and Practice in Thrombosis and Haemostasis","volume":"10 1","pages":"Article 103367"},"PeriodicalIF":3.4,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147309135","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Assessment of clinical probability scores for pulmonary embolism diagnosis during pregnancy and postpartum in women with a history of venous thromboembolism: a Highlow ancillary study","authors":"Fanny Collange ,&nbsp;Ingrid M. Bistervels ,&nbsp;Andrea Buchmuller ,&nbsp;Hanke M.G. Wiegers ,&nbsp;Fionnuala Ní Áinle ,&nbsp;Peter Verhamme ,&nbsp;Anne F. Jacobsen ,&nbsp;Anette T. Hansen ,&nbsp;Marc A. Rodger ,&nbsp;Maria T. DeSancho ,&nbsp;Roman G. Shmakov ,&nbsp;Luuk J.J. Scheres ,&nbsp;Celine Chauleur ,&nbsp;Saskia Middeldorp ,&nbsp;Bernard Tardy","doi":"10.1016/j.rpth.2025.103281","DOIUrl":"10.1016/j.rpth.2025.103281","url":null,"abstract":"<div><h3>Background</h3><div>The value of pretest clinical probability scores in the diagnosis of pulmonary embolism (PE) during pregnancy and postpartum is unknown in women with a history of venous thromboembolism (VTE).</div></div><div><h3>Objectives</h3><div>We evaluate the modified Wells, revised Geneva, and pregnancy-adapted Geneva (PAG) scores for the diagnosis of PE during pregnancy and the postpartum period in women with a history of VTE.</div></div><div><h3>Methods</h3><div>Data from a multicenter randomized trial (Highlow) including 1110 pregnant women with a history of VTE and treated with either weight-adjusted intermediate-dose or fixed low-dose low-molecular-weight heparin subcutaneously once daily until 6 weeks postpartum were used. The modified Wells, revised Geneva, and PAG scores were calculated retrospectively in all women with a clinical suspicion of PE, and their discriminative capacity was assessed. Receiver operating characteristic (ROC) curve analysis was performed for quantitative variables and the optimal threshold defined.</div></div><div><h3>Results</h3><div>There were 102 suspected cases of PE, of which 12 were confirmed events. During pregnancy, the ROC curves showed an area under the curve of 0.68, 0.33, and 0.36 for the Wells, Geneva, and PAG scores, respectively. During postpartum, the ROC curves showed an area under the curve of 0.75, 0.55, and 0.52 for the Wells, Geneva, and PAG scores, respectively.</div></div><div><h3>Conclusion</h3><div>The 3 pretest clinical scores have modest discriminatory power, during both the antepartum and the postpartum period, to classify patients into 3 categories of pretest clinical probability. Further work is required to develop clinical-decision tools to exclude imaging in pregnant women with prior VTE with suspected PE in pregnancy.</div></div>","PeriodicalId":20893,"journal":{"name":"Research and Practice in Thrombosis and Haemostasis","volume":"10 1","pages":"Article 103281"},"PeriodicalIF":3.4,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145927165","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Prevalence of abnormal uterine bleeding and quality of life after venous thromboembolism by oral anticoagulant use: the GENB-OAC Study","authors":"Gabrielle Sarlon-Bartoli ,&nbsp;Barbara Leclercq ,&nbsp;Nathalie Trillot ,&nbsp;Isabelle Mahé ,&nbsp;Marie Daoud-Elias ,&nbsp;Andrea Buchmuller ,&nbsp;Geraldine Poenou ,&nbsp;Antoine Elias ,&nbsp;Jean Noel Poggi ,&nbsp;Francis Couturaud ,&nbsp;Noemie Resseguier ,&nbsp;Martin Postzich ,&nbsp;Lylia Hammoudi ,&nbsp;Yasmine Benredouane ,&nbsp;Florence Bretelle ,&nbsp;Louisa Goumidi ,&nbsp;Pierre Suchon ,&nbsp;Sarah Jidal ,&nbsp;Antonia Perez-Martin ,&nbsp;Clementine Rousselin ,&nbsp;Pierre Emmanuel Morange","doi":"10.1016/j.rpth.2025.103328","DOIUrl":"10.1016/j.rpth.2025.103328","url":null,"abstract":"<div><h3>Background</h3><div>Anticoagulants cause abnormal uterine bleeding (AUB) in women of reproductive age with venous thromboembolism, but the safety profiles of oral anticoagulants (OACs) in this setting are unclear.</div></div><div><h3>Objectives</h3><div>To analyze and compare the prevalence of AUB and quality of life (QoL) in 4 groups (rivaroxaban, apixaban, vitamin K antagonists [VKAs], and controls).</div></div><div><h3>Methods</h3><div>The GENital Bleeding Oral AntiCoagulant (GENB-OAC) study was a national, multicenter, observational, cross-sectional study conducted in 10 French hospitals from 2018 to 2022. The primary outcome was the proportion of women with major genital bleeding and/or clinically relevant non-major genital bleeding and/or pictorial blood loss assessment chart score &gt;100.</div></div><div><h3>Results</h3><div>Overall, 445 women were included: 122 on apixaban, 123 on rivaroxaban, 81 taking VKAs, and 119 healthy controls. The primary genital bleeding endpoint was significantly higher in OAC vs control group (94.8% vs 82.4%; <em>P</em> &lt; .001) and the rivaroxaban or VKA vs apixaban group (96.7% or 97.5% vs 90.1%; <em>P</em> = .04 and <em>P</em> = .047). Major genital bleeding was similar in the apixaban and rivaroxaban groups, but menstruation ≥8 days, clinically relevant non-major bleeding, and pictorial blood loss assessment chart score &gt;100 were significantly higher in the rivaroxaban vs apixaban group. QoL was significantly lower in the OAC than in the control group but was similar in the 3 OAC groups.</div></div><div><h3>Conclusion</h3><div>AUB is frequent in women of reproductive age. OACs increase AUB and impact women’s QoL. Apixaban is associated with less AUB than rivaroxaban or VKAs with no difference in QoL. An international consensus is necessary to help clinicians detect and treat AUB in OAC users.</div></div>","PeriodicalId":20893,"journal":{"name":"Research and Practice in Thrombosis and Haemostasis","volume":"10 1","pages":"Article 103328"},"PeriodicalIF":3.4,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146078262","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The incidence of early recurrent venous thromboembolism: a systematic review and meta-analysis","authors":"Lisbeth Eischer ,&nbsp;Paul A. Kyrle ,&nbsp;Alexandra Kaider ,&nbsp;Anton Schmidt ,&nbsp;Brigitte Wildner ,&nbsp;Anja Boc ,&nbsp;Charlotte Bradbury ,&nbsp;Anetta Undas ,&nbsp;Francis Couturaud ,&nbsp;Matteo Nicola Dario Di Minno ,&nbsp;Geert-Jan Geersing ,&nbsp;David Jimenez ,&nbsp;Sameer Parpia ,&nbsp;Gualtiero Palareti ,&nbsp;Daniela Poli ,&nbsp;Daniel P. Potaczek ,&nbsp;Paolo Prandoni ,&nbsp;Sam Schulman ,&nbsp;Astrid van Hylckama Vlieg ,&nbsp;Michal Zabczyk ,&nbsp;Sabine Eichinger","doi":"10.1016/j.rpth.2025.103317","DOIUrl":"10.1016/j.rpth.2025.103317","url":null,"abstract":"<div><h3>Background</h3><div>Patients with venous thromboembolism (VTE) receive anticoagulation for at least 3 months. To evaluate recurrence risk thereafter, some strategies include D-dimer testing after discontinuing anticoagulation, which raises concern about early recurrence.</div></div><div><h3>Objectives</h3><div>To assess the incidence of recurrent VTE within 30 days after stopping anticoagulation.</div></div><div><h3>Methods</h3><div>We conducted a systematic review of EMBASE, CENTRAL, and MEDLINE to identify controlled trials and cohort studies of adult noncancer patients with deep vein thrombosis of the leg and/or pulmonary embolism treated with anticoagulants for ≥3 months. The primary outcome was symptomatic VTE within 30 days. The risk of bias was assessed using a modified version of the Newcastle-Ottawa Scale. Pooled recurrence rates were calculated using fixed random-effects meta-analyses.</div></div><div><h3>Results</h3><div>Of 42 studies, 24 (57%) provided data, encompassing 11,407 patients. Early recurrence occurred in 115 patients (1.01%), with a pooled incidence of 1.04% (95% CI, 0.8%-1.4%). Men had a risk similar to that of women (risk ratio, 1.2; 95% CI, 0.6-2.3; <em>P</em> = .7). Unprovoked VTE was associated with a 2.6-fold increase in risk (95% CI, 1.4-4.6; <em>P</em> &lt; .001) compared with provoked VTE. Patients with deep vein thrombosis at presentation had a similar risk of recurrence compared with those with an incident pulmonary embolism (risk ratio, 0.6; 95% CI: 0.3-1.2; <em>P</em> = .1). Findings regarding age were inconsistent. None of the recurrences was fatal. The overall risk of bias was low.</div></div><div><h3>Conclusion</h3><div>The incidence of early VTE recurrence after stopping anticoagulation is low. Temporarily discontinuing therapy to assess recurrence risk, therefore, appears safe and may aid in guiding treatment duration.</div></div>","PeriodicalId":20893,"journal":{"name":"Research and Practice in Thrombosis and Haemostasis","volume":"10 1","pages":"Article 103317"},"PeriodicalIF":3.4,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146078390","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The public health impact of cancer-associated venous thromboembolism: looking to the future","authors":"Alok A. Khorana","doi":"10.1016/j.rpth.2025.103299","DOIUrl":"10.1016/j.rpth.2025.103299","url":null,"abstract":"","PeriodicalId":20893,"journal":{"name":"Research and Practice in Thrombosis and Haemostasis","volume":"10 1","pages":"Article 103299"},"PeriodicalIF":3.4,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145885115","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Activated charcoal neutralization restores accurate Model for End-Stage Liver Disease and Child-Pugh scores in patients with cirrhosis on direct oral anticoagulant therapy","authors":"Capucine Habay ,&nbsp;Alix Riescher Tuczkiewicz ,&nbsp;Imen Ben Salah ,&nbsp;Catherine Trichet ,&nbsp;Juliette Gay ,&nbsp;François Durand ,&nbsp;Pierre-Emmanuel Rautou ,&nbsp;Olivier Roux ,&nbsp;Emmanuelle De Raucourt","doi":"10.1016/j.rpth.2025.103289","DOIUrl":"10.1016/j.rpth.2025.103289","url":null,"abstract":"<div><h3>Background</h3><div>The use of direct oral anticoagulants (DOACs) is increasingly common, including among patients with cirrhosis. These treatments interfere with coagulation tests, altering the Model for End-Stage Liver Disease (MELD) and Child-Pugh scores, which are critical for assessing disease severity and prioritizing patients on liver transplant waiting lists.</div></div><div><h3>Objective</h3><div>To evaluate the impact of rivaroxaban and apixaban on MELD and Child-Pugh scores and assess charcoal-based neutralization.</div></div><div><h3>Methods</h3><div>We investigated the <em>in vitro</em> impact of rivaroxaban and apixaban, at concentrations corresponding to peak plasma levels (300 ng/mL and 150 ng/mL, respectively), on the calculation of these scores. A total of 35 plasma samples from patients with cirrhosis (prothrombin level [PT%]: 13%-104%) were analyzed. INR (international normalized ratio) and PT% were measured before supplementation, after supplementation with rivaroxaban or apixaban, and after DOAC neutralization using activated charcoal (DOAC-Stop).</div></div><div><h3>Results</h3><div>Rivaroxaban and apixaban supplementation led to an increase in INR (median: 2.81 and 0.70, respectively), resulting in a median overestimation of the MELD score by 12 and 4 points, respectively. PT% was underestimated (median: 70% for rivaroxaban and 48% for apixaban), which impacted the Child-Pugh classification in 4 and 2 patients, respectively. Neutralization of rivaroxaban and apixaban with activated charcoal resulted in INR and PT% values that were comparable to baseline measurements and remained within the analytical variability of the method.</div></div><div><h3>Conclusion</h3><div>These findings highlight the importance of identifying patients on DOAC therapy and implementing neutralization techniques to avoid overestimating disease severity. DOAC-Stop effectively eliminates rivaroxaban- and apixaban-related interference, even in this specific population of patients with cirrhosis who sometimes have profoundly decreased PT% values. Failure to account for DOAC interference could lead to mismanagement and errors in prioritizing patients for liver transplantation.</div></div>","PeriodicalId":20893,"journal":{"name":"Research and Practice in Thrombosis and Haemostasis","volume":"10 1","pages":"Article 103289"},"PeriodicalIF":3.4,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145885199","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Malignancy and gene therapy in hemophilia","authors":"Radoslaw Kaczmarek","doi":"10.1016/j.rpth.2025.103283","DOIUrl":"10.1016/j.rpth.2025.103283","url":null,"abstract":"<div><div>Despite the misconception that adeno-associated virus (AAV) gene therapy vectors are nonintegrating, they can integrate into the host genome at a low but nonnegligible frequency, posing a theoretical risk of tumorigenesis. While AAV integration can trigger hepatocellular carcinoma in mice, no such association has been established in humans. None of the 10 cancer cases reported in AAV vector recipients so far has shown evidence that AAV integration drives tumorigenesis. However, the strength of the evidence from molecular analyses differed significantly across these cases. The scope and conclusiveness of causality assessments depended on sample quality and cross-validation using complementary analytical methods. For example, poor sample quality precluded a conclusive analysis in a case of a spinal cord tumor. Conversely, comprehensive analyses provided strong evidence that AAV integration was not the causative factor in a case of hepatocellular carcinoma. These findings underscore the need for standardization, global long-term follow-up, and careful communication of outcomes.</div></div>","PeriodicalId":20893,"journal":{"name":"Research and Practice in Thrombosis and Haemostasis","volume":"10 1","pages":"Article 103283"},"PeriodicalIF":3.4,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145885202","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Raising the D-dimer bar: a narrative review of the age-adjusted D-dimer threshold","authors":"Tayssir Fatah ,&nbsp;Judith Catella ,&nbsp;Christophe Nougier ,&nbsp;Hamdi Rezigue","doi":"10.1016/j.rpth.2025.103255","DOIUrl":"10.1016/j.rpth.2025.103255","url":null,"abstract":"<div><div>D-dimers play a key role in diagnosing venous thromboembolism (VTE) due to high negative predictive value in excluding VTE in patients with a nonhigh clinical probability. However, D-dimer levels naturally increase with age, complicating their interpretation in elderly patients. To address this, an age-adjusted threshold multiplying the patient’s age by 10 (μg/L), starting from age 50 years, has been proposed in several studies, to exclude the diagnosis of VTE in patients over 50 years with a nonhigh clinical probability. This narrative review discusses the establishment as well as the efficiency and safety of the age-adjusted threshold multiplying the patient’s age by 10 (μg/L), with a focus on the HemosIL D-dimer assays. Overall, the age-adjusted D-dimer threshold has demonstrated enhanced specificity without compromising sensitivity in excluding VTE in patients with suspected pulmonary embolism and nonhigh clinical probability in emergency department settings. By improving specificity, reducing imaging reliance, and lowering costs, the age-adjusted threshold offers a cost-effective and efficient strategy for optimizing VTE management. However, real-world diagnostic strategy studies remain limited, particularly for deep vein thrombosis. Retrospective studies dominate this area, and the cautious stance of scientific societies reflects the absence of large-scale, prospective trials. Emerging evidence suggests the age-adjusted threshold may be as safe and efficient as the conventional approach for deep vein thrombosis exclusion. More than 30 commercial assays are available for D-dimer testing, and the age-adjusted threshold is not validated with all commercially available D-dimer techniques. This underscores the critical need for assay-specific validation before age-adjusted thresholds can be reliably integrated into routine clinical practice.</div></div>","PeriodicalId":20893,"journal":{"name":"Research and Practice in Thrombosis and Haemostasis","volume":"10 1","pages":"Article 103255"},"PeriodicalIF":3.4,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145789244","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}