Research and Practice in Thrombosis and Haemostasis最新文献

{"title":"Anti-emicizumab antibodies and their relevance in clinical practice","authors":"Carla Valsecchi ,&nbsp;Lucia Schiavone ,&nbsp;Sara Arcudi ,&nbsp;Adriana Torri ,&nbsp;Cristina Novembrino ,&nbsp;Flora Peyvandi","doi":"10.1016/j.rpth.2025.103282","DOIUrl":"10.1016/j.rpth.2025.103282","url":null,"abstract":"<div><h3>Background</h3><div>Emicizumab is licensed for treatment of people with hemophilia A (HA) of all ages, with and without factor (F)VIII inhibitors. It is well tolerated, and most of the treatment-related adverse events are of mild intensity and transient. As for other therapeutic proteins, the potential of emicizumab to induce anti-drug antibodies (ADAs) should be considered when a decrease in treatment efficacy is observed. Data from 7 phase 3/3b pivotal studies showed that 5.1% of treated patients developed ADAs, &lt;1% being activity neutralizing. Among them, 1 case required discontinuation of emicizumab due to loss of treatment efficacy. To date, among several thousands of patients treated with emicizumab, 5 cases of ADAs requiring treatment discontinuation have been reported.</div></div><div><h3>Objectives</h3><div>Monitoring anti-emicizumab antibodies in 67 subjects with congenital HA who switched to emicizumab prophylaxis from FVIII products or bypassing agents.</div></div><div><h3>Methods</h3><div>The anti-emicizumab antibodies were tested, depending on patient availability, at baseline and longitudinally at 5, 10, 20, and 50 weeks after the first dose, as well as when clinically required.</div></div><div><h3>Results</h3><div>ADAs were detected in 4 of 67 cases (5.9%) on at least 2 occasions and were not necessarily associated to significant decreased emicizumab concentration, activated partial thromboplastin time prolongation or bleeding episodes. Only 1 of 4 ADA-positive patients required emicizumab discontinuation due to treatment failure.</div></div><div><h3>Conclusion</h3><div>The present findings confirm that the development of anti-emicizumab antibodies is a rare event, particularly those with neutralizing activity. Routine monitoring should be reserved only for patients with clinical manifestations of bleeding when therapy failure is suspected.</div></div>","PeriodicalId":20893,"journal":{"name":"Research and Practice in Thrombosis and Haemostasis","volume":"10 1","pages":"Article 103282"},"PeriodicalIF":3.4,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145885198","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":"Platelet function abnormalities in acquired hemophilia A","authors":"Raffaella Rossio ,&nbsp;Anna Lecchi ,&nbsp;Silvia La Marca ,&nbsp;Lidia Padovan ,&nbsp;Roberta Gualtierotti ,&nbsp;Cristina Novembrino ,&nbsp;Chiara Suffritti ,&nbsp;Sara Arcudi ,&nbsp;Alessandro Ciavarella ,&nbsp;Federico Boggio ,&nbsp;Simona Maria Siboni ,&nbsp;Flora Peyvandi","doi":"10.1016/j.rpth.2025.103293","DOIUrl":"10.1016/j.rpth.2025.103293","url":null,"abstract":"<div><h3>Background</h3><div>The bleeding pattern in acquired hemophilia A (AHA) differs from that of inherited hemophilia, being characterized by soft tissue and muscle hematomas, mucocutaneous bleeding, but seldom joint bleeding. Platelet function disorders are inherited or acquired. The acquired forms may appear in association with medications, medical conditions, and autoimmune disorders.</div></div><div><h3>Objectives</h3><div>We chose to investigate platelet function in a series of patients with AHA due to autoantibodies inactivating coagulation factor (F)VIII.</div></div><div><h3>Methods</h3><div>Platelet function disorders were assessed at AHA diagnosis in platelet-rich plasma according to the Scientific Subcommittee of the International Society on Thrombosis and Haemostasis recommendations. In addition, the δ- and α-granule platelet content—that is, adenine nucleotides (ADP and ATP), serotonin and β-thromboglobulin—were measured. CD40L and soluble P-selectin were also measured in plasma to investigate <em>in vivo</em> platelet activation.</div></div><div><h3>Results</h3><div>In 11 cases with AHA and a median age of 67 years, FVIII coagulant activity was unmeasurable, the inhibitor titer was &lt;20 Bethesda Units in 5 cases (45%) and higher than 20 Bethesda Units in 6 cases (55%). All patients showed reduced platelet aggregation and secretion. Furthermore, 4 cases with monoclonal gammopathy of undetermined significance had worse aggregation responses and an abnormal δ-granule platelet content, supporting a diagnosis of δ storage pool disease. Following remission the intraplatelet levels of ADP and serotonin improved.</div></div><div><h3>Conclusion</h3><div>This study demonstrates that acquired platelet function abnormalities may be present in patients with AHA and perhaps contribute to the severity of their bleeding tendency.</div></div>","PeriodicalId":20893,"journal":{"name":"Research and Practice in Thrombosis and Haemostasis","volume":"10 1","pages":"Article 103293"},"PeriodicalIF":3.4,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145927163","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":"Factor VIII and von Willebrand factor activity levels during long-term prophylaxis with wilate—Analyses from the WIL-31 study","authors":"Robert F. Sidonio Jr. ,&nbsp;Ana Boban ,&nbsp;Claudia Djambas Khayat ,&nbsp;WIL-31 Study Investigators","doi":"10.1016/j.rpth.2025.103327","DOIUrl":"10.1016/j.rpth.2025.103327","url":null,"abstract":"<div><h3>Background</h3><div>Long-term von Willebrand factor (VWF) prophylaxis is recommended for people with von Willebrand disease (VWD) who experience frequent and severe bleeds. However, repeated administration of VWF-containing concentrates may lead to VWF and/or factor (F)VIII accumulation, with an increased thrombotic risk. Data on FVIII and VWF accumulation during prophylaxis in VWD are lacking.</div></div><div><h3>Objectives</h3><div>This study analyzed FVIII and VWF activity levels during long-term prophylaxis with wilate, a plasma-derived VWF/FVIII concentrate containing VWF and FVIII in a physiological 1:1 activity ratio, in the prospective WIL-31 study.</div></div><div><h3>Methods</h3><div>Preinjection and postinjection FVIII and VWF activity levels were measured in plasma at baseline and after 1, 2, 3, 6, 9, and 12 months of wilate in the 33 patients who completed WIL-31. Analyses were descriptive and included stratification by age and VWD type.</div></div><div><h3>Results</h3><div>VWF and FVIII activity levels (IU/dL) remained stable during 12 months of prophylaxis. Mean (SD) VWF activity levels preinjection and postinjection were 6.7 (4.0) and 59.0 (28.7) at baseline and 8.6 (7.6) and 44.4 (20.5) at 12 months, respectively. For FVIII, levels were 13.2 (18.9) and 75.5 (31.3) at baseline and 27.5 (25.6) and 83.6 (30.0) at 12 months, respectively. Similarly, when stratified by age and VWD type, no accumulation of either factor was observed. No thrombotic events were reported.</div></div><div><h3>Conclusions</h3><div>During 12 months of wilate prophylaxis, there was no accumulation of FVIII or VWF regardless of age and VWD type, and no thrombotic events were reported. These findings from WIL-31 confirm and extend wilate’s existing safety data.</div></div>","PeriodicalId":20893,"journal":{"name":"Research and Practice in Thrombosis and Haemostasis","volume":"10 1","pages":"Article 103327"},"PeriodicalIF":3.4,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145978193","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":"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":"The Ottawa score for prediction of recurrent venous thromboembolism in cancer patients treated with tinzaparin: an individual patient data meta-analysis","authors":"Céline Chapelle ,&nbsp;Philippe Girard ,&nbsp;Luis Jara-Palomares ,&nbsp;Agnès Y.Y. Lee ,&nbsp;Olivier Sanchez ,&nbsp;Guy Meyer ,&nbsp;Géraldine Poenou ,&nbsp;Patrick Mismetti ,&nbsp;Isabelle Mahé ,&nbsp;Silvy Laporte","doi":"10.1016/j.rpth.2025.103278","DOIUrl":"10.1016/j.rpth.2025.103278","url":null,"abstract":"<div><h3>Background</h3><div>Risk of venous thromboembolism (VTE) recurrence remains high in patients with cancer-associated thrombosis (CAT), despite therapeutic anticoagulation. Identifying patients at risk of treatment failure is still a challenge.</div></div><div><h3>Objectives</h3><div>We aimed to assess the performance of the Ottawa score in predicting VTE recurrence in a large homogeneous population of patients with CAT treated with the same anticoagulant, tinzaparin, for at least 3 months.</div></div><div><h3>Methods</h3><div>Individual patient data from 3 prospective cohort studies and 1 randomized controlled trial were pooled (PROSPERO: CRD42019119907). Clinical events of interest were adjudicated by independent central adjudication committees in all 4 studies.</div></div><div><h3>Results</h3><div>Among the 1413 patients included, the Ottawa score could be calculated for 1088 of whom 646 (59.4%) were classified at high risk of recurrence (Ottawa score ≥ 1). The 6-month cumulative incidence of recurrent VTE was 5.0% (95% CI, 3.2-7.8) in the Ottawa low-risk group and 8.5% (95% CI, 6.6-10.8) in the high-risk group. The area under the receiver operating characteristic curve was 0.56 (95% CI, 0.51-0.62). The sensitivity of the dichotomized Ottawa score (score ≥ 1) was 72.8% (95% CI, 62.6%-83.0%), the specificity was 41.9% (95% CI, 37.8%-45.9%), the positive predictive value was 8.6% (95% CI, 6.4%-10.8%), and the negative predictive value was 95.3% (95% CI, 93.3%-97.4%). Introducing additional predictive factors failed to significantly improve the score’s performance.</div></div><div><h3>Conclusions</h3><div>Despite the large number of patients and anticoagulant treatment standardization, the Ottawa score failed to accurately predict recurrent VTE in patients with CAT treated with tinzaparin.</div></div>","PeriodicalId":20893,"journal":{"name":"Research and Practice in Thrombosis and Haemostasis","volume":"10 1","pages":"Article 103278"},"PeriodicalIF":3.4,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145978191","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":"High-density lipoprotein subfractions and risk of future venous thromboembolism—the HUNT study","authors":"Inga A. Røstvold ,&nbsp;Ben Brumpton ,&nbsp;Kristian Hveem ,&nbsp;Bjørn Olav Åsvold ,&nbsp;Guro F. Giskeødegård ,&nbsp;George Davey Smith ,&nbsp;Nicholas J. Timpson ,&nbsp;Kaitlin H. Wade ,&nbsp;John-Bjarne Hansen ,&nbsp;Sigrid K. Brækkan","doi":"10.1016/j.rpth.2025.103295","DOIUrl":"10.1016/j.rpth.2025.103295","url":null,"abstract":"<div><h3>Background</h3><div>Previous studies on high-density lipoprotein (HDL) cholesterol levels and the risk of venous thromboembolism (VTE) have shown conflicting results, and it has been suggested that specific HDL subfractions and lipid composition may be more informative with regards to VTE risk.</div></div><div><h3>Objectives</h3><div>We aimed to investigate the association between HDL subfractions (including particle size, concentration, and lipid composition) and risk of VTE in a population-based cohort.</div></div><div><h3>Methods</h3><div>The study included 17,032 participants from the Trøndelag Health Study (HUNT3) cohort conducted in 2006-2008 who were followed up until December 31, 2019. HDL subfractions were analyzed in serum using nuclear magnetic resonance spectroscopy. All incident VTEs during follow-up were validated and recorded. Cox proportional hazards regression models estimated hazard ratios (HRs) for the association between HDL metrics and incident VTE, adjusting for age, sex, and body mass index.</div></div><div><h3>Results</h3><div>During a median follow-up of 12.0 years, 342 incident VTE cases were confirmed. No associations were found among HDL particle size, HDL concentration, HDL lipid composition, apolipoprotein (Apo)A1 levels, and VTE risk. All HRs per 1-SD increase in HDL metrics were within the range of 0.83 to 1.16 and had 95% CIs that included 1. Furthermore, quartile analyses of HDL particles (Q4 vs Q1—HR, 0.89; 95% CI, 0.65-1.21) and ApoA1 (Q4 vs Q1—HR, 0.94; 95% CI, 0.68-1.29) showed no associations with VTE risk.</div></div><div><h3>Conclusion</h3><div>HDL subfractions, including particle size, concentration, lipid composition, and ApoA1, were not associated with the risk of a first-lifetime VTE event.</div></div>","PeriodicalId":20893,"journal":{"name":"Research and Practice in Thrombosis and Haemostasis","volume":"10 1","pages":"Article 103295"},"PeriodicalIF":3.4,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145885114","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":"Safety and efficacy of direct oral anticoagulants in patients with liver cirrhosis: a meta-analysis","authors":"Daniel Tham ,&nbsp;Wenhui Yu ,&nbsp;Lucy Zhao ,&nbsp;Roger Kou ,&nbsp;Jayhan Kherani ,&nbsp;Pei Yi Li ,&nbsp;Shreyas Sreeraman ,&nbsp;Ali Eshaghpour ,&nbsp;Allen Li ,&nbsp;Mark A. Crowther","doi":"10.1016/j.rpth.2025.103296","DOIUrl":"10.1016/j.rpth.2025.103296","url":null,"abstract":"<div><h3>Background</h3><div>Direct oral anticoagulants (DOACs) are the standard of care for treatment of venous thromboembolism and stroke prophylaxis in atrial fibrillation. Since patients with Child-Pugh (CP) B or C liver cirrhosis are underrepresented in trials, the safety of DOACs in this population is unclear.</div></div><div><h3>Objectives</h3><div>This study synthesized primary evidence on the safety profile of DOACs in patients with advanced liver cirrhosis.</div></div><div><h3>Methods</h3><div>A literature search of MEDLINE and Embase from inception to October 2025 identified randomized and nonrandomized cohort studies comparing DOAC with vitamin K antagonists or low-molecular-weight heparin in patients with liver cirrhosis. Screening and data collection were conducted in duplicate. The primary outcome was major bleeding defined by International Society on Thrombosis and Haemostasis criteria, stratified by CP class. Data were meta-analyzed using a random-effects model, presented as odds ratios (OR) with corresponding 95% CIs.</div></div><div><h3>Results</h3><div>Of 797 articles captured in the literature search, 15 nonrandomized (<em>n</em> = 17,387) and 1 randomized (<em>n</em> = 70) study were included. DOACs reduced major bleeding in both CP class B and C exclusive subgroup and a subgroup with unspecified CP stages of liver cirrhosis (CP B and C: OR, 0.53; 95% CI, 0.36-0.80; CP unspecified: OR, 0.66; 95% CI, 0.46-0.98).</div></div><div><h3>Conclusion</h3><div>Based on the findings of this meta-analysis, DOACs may be associated with a reduced risk of major bleeding compared with vitamin K antagonists or low-molecular-weight heparin in patients with liver cirrhosis, including those with CP class B and C cirrhosis. The results of this meta-analysis should be interpreted in the context of methodological limitations. Future analysis should evaluate the impact of specific DOACs and dosage on safety outcomes in this patient population.</div></div>","PeriodicalId":20893,"journal":{"name":"Research and Practice in Thrombosis and Haemostasis","volume":"10 1","pages":"Article 103296"},"PeriodicalIF":3.4,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145885196","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}