Journal of Thrombosis and Haemostasis最新文献

{"title":"Anticoagulant drugs targeting factor XI/XIa and coagulation tests: we urgently need reliable pharmacodynamic data","authors":"Isabelle Gouin-Thibault ,&nbsp;Thomas Lecompte ,&nbsp;Dominique Lasne","doi":"10.1016/j.jtha.2025.02.025","DOIUrl":"10.1016/j.jtha.2025.02.025","url":null,"abstract":"<div><div>Antifactor (F)XI/FXIa anticoagulants under development include antisense oligonucleotides, monoclonal antibodies, and small molecules. They do not require routine monitoring, but knowledge of their impact on coagulation tests is essential in view of their expected widespread use. A concentration-dependent prolongation of activated partial thromboplastin time has been shown but varies according to reagents, and the lack of comprehensive data makes interpretation of this test difficult. Measurement of FXI clotting activity is relevant only in case of treatment with antisense oligonucleotides. Measurement of contact pathway factors, if required, should be performed after multiple dilutions of the plasma sample to overcome any inhibitory effect of the anticoagulant. All other tests used in clinical trials (FXIa, FXI antigenic method, and specific thrombin generation assay) are not implemented in clinical laboratories.</div><div>More comprehensive information on the effect of anti-FXI/FXIa anticoagulants on coagulation tests is urgently needed to anticipate the use of these drugs once they are approved.</div></div>","PeriodicalId":17326,"journal":{"name":"Journal of Thrombosis and Haemostasis","volume":"23 5","pages":"Pages 1464-1468"},"PeriodicalIF":5.5,"publicationDate":"2025-03-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143586174","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":"Activated factor XI-antithrombin and thrombin-antithrombin complexes in the prediction of venous thromboembolism and mortality in patients with non-small-cell lung cancer.","authors":"Patricia Gomez-Rosas, Magdolna Nagy, Henry M H Spronk, Laura Russo, Sara Gamba, Carmen Julia Tartari, Silvia Bolognini, Chiara Ticozzi, Francesca Schieppati, Roberta Sarmiento, Filippo De Braud, Giovanna Masci, Carlo Tondini, Fausto Petrelli, Francesco Giuliani, Andrea D'Alessio, Armando Santoro, Giampietro Gasparini, Roberto Labianca, Hugo Ten Cate, Anna Falanga, Marina Marchetti","doi":"10.1016/j.jtha.2025.02.029","DOIUrl":"10.1016/j.jtha.2025.02.029","url":null,"abstract":"<p><strong>Background: </strong>Patients with non-small cell lung cancer (NSCLC) are at high risk of venous thromboembolism (VTE), especially during chemotherapy. Even though the contact system is implicated in the pathogenesis of thrombosis, limited data are available on the role of contact system activation in NSCLC-associated VTE.</p><p><strong>Objectives: </strong>In a prospective cohort of patients with NSCLC starting chemotherapy, contact system activation and thrombin generation biomarkers were assessed in relation to 6-month VTE occurrence and mortality.</p><p><strong>Methods: </strong>Prechemotherapy plasma samples of 719 newly diagnosed patients with NSCLC were tested for in vivo biomarkers of contact system activation (ie, kallikrein [pKa]:antithrombin [AT; PKa:AT], activated factor [F]XI:AT [FXIa:AT], FXIa:C1-esterase inhibitor C1Inh [FXIa:C1Inh], activated FIX:AT [FIXa:AT]), and thrombin generation (ie, prothrombin fragment 1+2 [F1+2] and thrombin-antithrombin complex [TAT]). Clinical data, VTE, and mortality were recorded prospectively.</p><p><strong>Results: </strong>The 6-month VTE and mortality cumulative incidences were 11% and 27%, respectively. Basal levels of FXIa:AT complexes, F1+2, and TAT were higher in patients who developed VTE than those in VTE-free patients. Differently, PKa:AT, FIXa:AT, and TAT were lower in survivors than those in nonsurvivors. The multivariable analysis identified FXIa:AT (subdistribution hazard ratio, 1.17; 95% CI, 1.00-1.37) and TAT (subdistribution hazard ratio, 1.28; 95% CI, 1.10-1.50) as VTE-independent risk factors during chemotherapy. A score based on these biomarkers was generated, which was able to discriminate patients at significantly higher rates of VTE and mortality.</p><p><strong>Conclusion: </strong>Elevated in vivo contact pathway activation and thrombin generation were observed in patients with NSCLC who developed VTE. Furthermore, a score based on both FXIa:AT and TAT levels was developed to identify those patients at higher risk of VTE and mortality.</p>","PeriodicalId":17326,"journal":{"name":"Journal of Thrombosis and Haemostasis","volume":" ","pages":""},"PeriodicalIF":5.5,"publicationDate":"2025-03-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143586168","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 glycoprotein VI signaling defect in newly formed platelets generated in stress thrombopoiesis.","authors":"Stephanie R Hyslop, Jason Corbin, Pradnya Gangatirkar, Marion Lebois, Amanda E Au, Diane Moujalled, Irina Pleines, Kate D Sutherland, Robert K Andrews, Elizabeth E Gardiner, Warren S Alexander, Emma C Josefsson","doi":"10.1016/j.jtha.2025.02.035","DOIUrl":"10.1016/j.jtha.2025.02.035","url":null,"abstract":"<p><strong>Background: </strong>Newly produced platelets are thought to be more functional than their older counterparts. However, recent work suggests that murine platelets formed following immune-mediated thrombocytopenia possess a transient glycoprotein (GP) VI signaling defect.</p><p><strong>Objectives: </strong>In this study, we explored whether other models of stress thrombopoiesis would generate platelets that display a functional defect.</p><p><strong>Methods: </strong>Platelet function was assessed by light transmission aggregometry and/or flow cytometry in genetic and disease models of thrombocytopenia and after chemotherapy-induced thrombocytopenia.</p><p><strong>Results: </strong>We evaluated platelet function in mice bearing a point mutation in Bcl-x and in 2 cancer models, all presenting with thrombocytopenia and a high proportion of reticulated platelets. Flow cytometric analysis of platelet degranulation and integrin activation revealed a significantly diminished response to the GPVI agonist convulxin in all models, but not thrombin. Likewise, platelet aggregation and Syk phosphorylation downstream of GPVI, in response to convulxin, was significantly reduced. Furthermore, a rebound from carboplatin-induced or immune-mediated thrombocytopenia caused a transient GPVI defect. The Mpl^-/- model of thrombocytopenia (with a normal proportion of reticulated platelets) was included as a negative control. In response to convulxin, Mpl^-/- platelets exhibited normal degranulation and integrin activation.</p><p><strong>Conclusion: </strong>In this study, we report a functional defect in platelet GPVI signaling present in multiple models of thrombocytopenia that are accompanied by an increased proportion of rapidly generated young platelets. These results indicate that during stress thrombopoiesis, the GPVI receptor becomes entirely functional only after spending some time in circulation.</p>","PeriodicalId":17326,"journal":{"name":"Journal of Thrombosis and Haemostasis","volume":" ","pages":""},"PeriodicalIF":5.5,"publicationDate":"2025-03-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143586165","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":"Discrepancy between one-stage clotting and chromogenic factor VIII activity in women with hemophilia A and hemophilia A carriers: a retrospective clinical study.","authors":"Stephanie Desage, Anne Lienhart, Maissaa Janbain, Hamdi Rezigue, Alexandre Leuci, Yesim Dargaud","doi":"10.1016/j.jtha.2025.02.031","DOIUrl":"10.1016/j.jtha.2025.02.031","url":null,"abstract":"<p><strong>Background: </strong>For every man diagnosed with hemophilia, approximately 1.6 women are expected to be carriers. Carriers are classified based on their factor (F) VIII levels and symptoms, ranging from asymptomatic to mild, either moderate or severe symptoms. Close monitoring is critical for carriers with low FVIII levels or bleeding symptoms, as the bleeding risk is difficult to assess due to inconsistent correlations with routine one-step assay (OSA) measurements.</p><p><strong>Objectives: </strong>This study hypothesized that the chromogenic FVIII assay (CSA) may provide valuable information for estimating the bleeding risk in some hemophilia carriers.</p><p><strong>Methods: </strong>This retrospective study included 109 hemophilia A carriers from 2 centers.</p><p><strong>Results: </strong>Among them, 23% had FVIII levels <40 IU/dL when assessed using OSA, while 41% showed discrepancies when assessed using CSA. von Willebrand factor activity and antigen levels were normal, with mean values of 84 IU/dL and 107, respectively. There was a significant correlation between OSA and CSA FVIII results, although 20 women had discordant results between the 2 methods. Bleeding events were reported in 49 women, including 18 surgical complications, 1 joint bleeding episode, and 30 cases of heavy menstrual bleeding, all occurring with normal von Willebrand factor levels. There were 157 pregnancies in which 14 cases of postpartum hemorrhage were observed, 3 of which required transfusion or surgery.</p><p><strong>Conclusion: </strong>This study highlights the significant discrepancies between OSA and CSA in FVIII results, with implications for diagnosis and bleeding risk assessment. It emphasizes the need to use both methods to identify women at a higher risk of bleeding, especially before surgery.</p>","PeriodicalId":17326,"journal":{"name":"Journal of Thrombosis and Haemostasis","volume":" ","pages":""},"PeriodicalIF":5.5,"publicationDate":"2025-03-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143586195","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":"An engineered Treg selective immunocytokine induces sustained immune modulation in a preclinical model of hemophilia A.","authors":"Jyoti Rana, Derek VanDyke, Maite Muñoz-Melero, Charina S Fabilane, Senthilkumar Thirumurugan, Sreevani Arisa, Baohua Zhou, Jamie B Spangler, Moanaro Biswas","doi":"10.1016/j.jtha.2025.02.032","DOIUrl":"10.1016/j.jtha.2025.02.032","url":null,"abstract":"<p><strong>Background: </strong>The development of inhibitory antibodies (inhibitors) is a serious complication in the treatment of hemophilia A with clotting factor (F)VIII replacement therapy. Inhibitor formation critically depends on T cell help and modulation by regulatory T cells (Tregs).</p><p><strong>Objectives: </strong>In this study, we evaluated the F5111 immunocytokine (IC), a single-chain fusion between the human interleukin (IL)-2 cytokine and an IL-2 antibody that biases cytokine activity toward cells with high IL-2 receptor (IL-2R)α expression, leading to extended IL-2 half-life and selective expansion of Tregs.</p><p><strong>Methods: </strong>A transient F5111 IC administration regimen was applied to a hemophilia A murine model of FVIII replacement therapy. Inhibitory antibody development to FVIII was monitored longitudinally by Bethesda assay and ELISA.</p><p><strong>Results: </strong>F5111 IC failed to stimulate cell types that predominantly express the dimeric IL2Rβγ receptor complex such as effector T and natural killer cells. Potent and highly transient Treg expansion was associated with suppression of effector T cells and in vivo conversion into Tregs. When tested in the hemophilia A mouse model, F5111 IC completely prevented the formation of inhibitors against FVIII for up to 4 months, long after Treg numbers returned to baseline levels.</p><p><strong>Conclusion: </strong>These results demonstrate that F5111 IC induces a superior and prolonged tolerogenic response compared with an unbiased control IC. Overall, this study presents a novel and effective strategy for preventing inhibitory antibodies that hinder the effectiveness of FVIII replacement therapy in hemophilia A.</p>","PeriodicalId":17326,"journal":{"name":"Journal of Thrombosis and Haemostasis","volume":" ","pages":""},"PeriodicalIF":5.5,"publicationDate":"2025-03-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143586171","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":"Patients with cirrhosis have a disbalance between coagulation and fibrinolysis resulting in a prothrombotic phenotype.","authors":"Ruth Anne Laura Willems, Alberto Zanetto, Elena Campello, Ilaria de Simone, Cristiana Bulato, Joke Konings, Matthijs Kramer, Samia Tufaha, Francesco Paolo Russo, Marco Senzolo, Patrizia Burra, Hugo Ten Cate, Judith de Vos-Geelen, Mark Roest, Paolo Simioni, Bas de Laat, Dana Huskens","doi":"10.1016/j.jtha.2025.02.034","DOIUrl":"10.1016/j.jtha.2025.02.034","url":null,"abstract":"<p><strong>Background: </strong>Patients with cirrhosis develop multiple hemostatic alterations. Although fibrinolysis is also affected by liver disease, studies have produced conflicting results, highlighting the need for a reliable fibrinolysis assay. Assessing the kinetics of plasmin generation (PG) is a new method to study the fibrinolytic state of cirrhosis patients.</p><p><strong>Objectives: </strong>This study aimed to compare fibrinolysis between patients with cirrhosis and healthy subjects.</p><p><strong>Methods: </strong>This single-center cohort study included cirrhosis patients from the Padova University Hospital. Fibrinolysis and hemostasis were assessed with PG, thrombin generation (TG), and clot lysis time. To quantify malalignment between TG and PG, ratios were calculated.</p><p><strong>Results: </strong>In total, 101 patients with cirrhosis (Child-Pugh A/B/C: 36/24/41) and 20 healthy subjects were included. Compared with healthy subjects, patients showed a significantly lower endogenous plasmin potential and plasmin peak. The PG capacity decreased with liver disease severity. The lag time to PG was prolonged in patients. No differences in endogenous thrombin potential and lag time were found when comparing TG profiles. Patients had a shorter clot lysis time. Increased TG/PG ratios for the endogenous plasmin potential and plasmin peak were found in patients compared with that in controls. TG/PG ratios increased with liver disease severity.</p><p><strong>Conclusion: </strong>Patients with cirrhosis have a complex fibrinolytic profile, with a delayed and decreased capacity to generate plasmin and a more rapid clot lysis. A disbalance was found between coagulation and fibrinolysis, with a normal-to-increased TG capacity and a decreased PG capacity. These results support the theory that cirrhosis patients are in a prothrombotic state.</p>","PeriodicalId":17326,"journal":{"name":"Journal of Thrombosis and Haemostasis","volume":" ","pages":""},"PeriodicalIF":5.5,"publicationDate":"2025-03-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143586202","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":"Discrepancy between parallel anti-Xa and activated partial thromboplastin time is related to mortality in patients with Impella-supported cardiogenic shock.","authors":"Charlotte J Van Edom, Francesca Fiorelli, Tim Balthazar, Maria Monteagudo-Vela, Thomas Vanassche, Vasileios F Panoulas, Christophe Vandenbriele","doi":"10.1016/j.jtha.2025.02.028","DOIUrl":"10.1016/j.jtha.2025.02.028","url":null,"abstract":"<p><strong>Background: </strong>Managing unfractionated heparin (UFH) during percutaneous mechanical circulatory support for cardiogenic shock (CS) is challenging due to potential discrepancies between coagulation tests.</p><p><strong>Objectives: </strong>To study the causes and consequences of discrepancies between anti-Xa and activated partial thromboplastin time (APTT) for UFH monitoring during microaxial flow pump support (Impella) for CS.</p><p><strong>Methods: </strong>We assessed patients in CS supported with Impella in 2 tertiary care centers over 62 months. UFH was titrated based on anti-Xa levels with parallel APTT measurements. In-range anti-Xa levels were considered between 0.20 and 0.30 IU/mL or 0.31 and 0.50IU/mL, and the corresponding APTT values were 40 to 55 seconds and 56 to 80 seconds, respectively. Pearson correlation was calculated between anti-Xa and APTT. Samples with in-range anti-Xa but prolonged APTT were analyzed for abnormalities in international normalized ratio (INR; ≥1.5) and/or fibrinogen (<1.5g/L). Mortality during Impella support was then compared in those with and without additional coagulation abnormalities (chi-squared test).</p><p><strong>Results: </strong>Correlation between anti-Xa and APTT was weak (r = 0.50, P < .001, N = 2447). When anti-Xa was in range (N = 1914 samples), 24% had short, 52% had in-range, and 24% had prolonged APTT. Of the 57 patients with prolonged APTT, 28 had abnormal same-day INR and/or fibrinogen, whereas 29 had normal fibrinogen and INR. Mortality was higher in patients with abnormal INR and/or fibrinogen than in those with normal fibrinogen and INR (32% vs 10%; P = .043).</p><p><strong>Conclusion: </strong>Anti-Xa/APTT discrepancies are frequent during percutaneous mechanical circulatory support for CS, highlighting the importance of a multiple testing strategy. Outcomes of patients with prolonged APTT were related to the presence of abnormal INR and/or fibrinogen, suggesting a serious concomitant underlying disease.</p>","PeriodicalId":17326,"journal":{"name":"Journal of Thrombosis and Haemostasis","volume":" ","pages":""},"PeriodicalIF":5.5,"publicationDate":"2025-03-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143586197","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 and radiologic characteristics of chronic thromboembolic pulmonary hypertension patients without a history of acute venous thromboembolism.","authors":"Coen van Kan, Josien van Es, Hachim El Idrissi, Dieuwertje Ruigrok, Esther J Nossent, Jurjan Aman, Frederikus A Klok, Harm Jan Bogaard, Lilian J Meijboom, Anton Vonk-Noordegraaf","doi":"10.1016/j.jtha.2025.02.033","DOIUrl":"10.1016/j.jtha.2025.02.033","url":null,"abstract":"<p><strong>Background: </strong>Chronic thromboembolic pulmonary hypertension (CTEPH) is thought to result from incomplete resolution of vascular obstruction following acute pulmonary embolism. However, at least 25% of patients with CTEPH do not have a documented episode of acute venous thromboembolism (VTE).</p><p><strong>Objectives: </strong>We hypothesized that patients without a VTE in their past medical history have different clinical and radiologic characteristics compared with patients with CTEPH with previous acute VTE.</p><p><strong>Methods: </strong>Baseline data and the history of VTE were retrospectively retrieved from the charts of all patients with CTEPH included between 2014 and 2022 in the Amsterdam University Medical Center CTEPH registry. Computed tomography pulmonary angiography, right heart catheterization, and pulmonary function tests were performed in all patients. Subsegmental disease was defined by the presence of a contrast defect in the pulmonary arterial vessels after the first arterial branch division.</p><p><strong>Results: </strong>A total of 262 patients with CTEPH were included; 47 patients (18%) did not have previous acute VTE. Baseline radiologic assessment showed that subsegmental disease was more frequent in patients without previous VTE (n = 16/43; 35%, 95% CI: 22-49) than in patients with previous VTE (n = 27/214; 13% [95% CI: 9.0-18], OR: 2.6 [95% CI: 1.2-5.7]). The patients without previous VTE were less frequently assigned to pulmonary endarterectomy than patients with acute VTE (30% [95% CI: 18-44] vs 56% [95% CI: 49-62]; OR: 0.5 [95% CI: 0.2-0.9]). Comorbidities, pulmonary function, and hemodynamics were not different.</p><p><strong>Conclusion: </strong>Patients with CTEPH without previous VTE had more distally located disease on imaging than patients with CTEPH with previous VTE and were less often subjected to pulmonary endarterectomy.</p>","PeriodicalId":17326,"journal":{"name":"Journal of Thrombosis and Haemostasis","volume":" ","pages":""},"PeriodicalIF":5.5,"publicationDate":"2025-03-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143586180","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":"Bleeding symptoms in persons with rare bleeding disorders and a heterozygous genotype: data from the Rare Bleeding Disorders in the Netherlands study.","authors":"Sterre P E Willems, Marjon H Cnossen, Nick van Es, Paul L den Exter, Ilmar C Kruis, Dominique P M S M Maas, Karina Meijer, Laurens Nieuwenhuizen, Sanna Rijpma, Joline L Saes, Annet Simons, Roger E G Schutgens, Marjan Weiss, Nicole M A Blijlevens, Waander L van Heerde, Saskia E M Schols","doi":"10.1016/j.jtha.2025.02.030","DOIUrl":"10.1016/j.jtha.2025.02.030","url":null,"abstract":"<p><strong>Background: </strong>Limited data exist on persons with rare bleeding disorders possessing a heterozygous genotype, as most studies focus on biallelic genotypes and more severe coagulation factor deficiencies. A growing body of evidence suggests that persons with a heterozygous genotype experience clinically relevant bleeding symptoms.</p><p><strong>Objectives: </strong>This study aimed to explore the incidence of bleeding symptoms and postoperative bleeding in persons with a heterozygous genotype.</p><p><strong>Methods: </strong>This cross-sectional substudy of the Rare Bleeding Disorders in the Netherlands study (2017-2019) included persons with rare coagulation factor deficiencies and disorders of fibrinolysis with a heterozygous or biallelic genotype. Clinical data and laboratory samples were collected during a single study visit along with questionnaires.</p><p><strong>Results: </strong>In total, 86 persons with a heterozygous genotype and 55 with a biallelic genotype were included. Median factor activity levels in persons with a heterozygous genotype approached 50% with considerable heterogeneity (range, 11%-93%). In 75%, persons with a heterozygous genotype reported bleeding severity of grade II or III. Female-specific bleeding was common. In total, 425 surgical procedures were performed. Persons with a heterozygous genotype were less likely to receive periprocedural treatment, and omission of periprocedural treatment was associated with postoperative bleeding in procedures with intermediate-high bleeding risk. Postoperative bleeding was comparable for persons with a heterozygous genotype (35%; 59/171) and a biallelic genotype (35%; 86/247; P = .926).</p><p><strong>Conclusion: </strong>In our population with rare bleeding disorders, the majority of persons possessing a heterozygous genotype exhibited spontaneous bleeding symptoms. Especially in intermediate-high risk procedures, a proactive approach to periprocedural hemostatic treatment in persons with a heterozygous genotype seems beneficial.</p>","PeriodicalId":17326,"journal":{"name":"Journal of Thrombosis and Haemostasis","volume":" ","pages":""},"PeriodicalIF":5.5,"publicationDate":"2025-03-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143586177","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 and outcomes after on-treatment recurrent venous thromboembolism in patients with cancer: a post hoc analysis of the Hokusai venous thromboembolism cancer study.","authors":"Vincent R Lanting, Kika van Bergen En Henegouwen, Floris T M Bosch, Michael A Grosso, Annelise Segers, Gary E Raskob, T Pieter Willem Kamphuisen, Harry R Büller, Peter Verhamme, Jeffrey I Weitz, Marcello Di Nisio, Marc Carrier, Nick van Es, Tzu-Fei Wang","doi":"10.1016/j.jtha.2025.02.022","DOIUrl":"10.1016/j.jtha.2025.02.022","url":null,"abstract":"<p><strong>Background: </strong>The management of recurrent venous thromboembolism (VTE) despite anticoagulant treatment in patients with cancer is uncertain. To address this, we used data from the Hokusai VTE Cancer trial, which compared edoxaban with dalteparin to treat cancer-associated VTE.</p><p><strong>Objectives: </strong>To characterize and evaluate anticoagulant treatment strategies during and after on-treatment recurrent VTE, including the type and dose of anticoagulant.</p><p><strong>Methods: </strong>In this post hoc analysis, all patients with adjudicated on-treatment recurrent VTE within 12 months after randomization were included. Outcomes were second recurrent VTE and major bleeding within 3 months after the first recurrent VTE.</p><p><strong>Results: </strong>A total of 67 patients developed on-treatment recurrent VTE while receiving therapeutic-dose edoxaban (31%), therapeutic-dose low-molecular-weight heparin (LMWH) (34%), maintenance-dose LMWH (21%), or other therapies (14%). After the recurrent event, 28 patients (42%) received an increased dose, 35 (52%) a comparable dose, and 4 (6%) a reduced dose or stopped anticoagulants. Common treatment regimens included supratherapeutic-dose LMWH (21%), therapeutic-dose LMWH (51%), direct oral anticoagulants (16%), or another treatment strategy (12%). In the 3 months after recurrent VTE, 6 (9%) patients had a second recurrence and 7 (10%) had major bleeding.</p><p><strong>Conclusion: </strong>Treatment strategies for recurrent VTE in patients with cancer are heterogeneous. The risk of a second recurrence and major bleeding are considerable. More studies are needed to determine the optimal treatment strategy for recurrent cancer-associated thrombosis.</p>","PeriodicalId":17326,"journal":{"name":"Journal of Thrombosis and Haemostasis","volume":" ","pages":""},"PeriodicalIF":5.5,"publicationDate":"2025-03-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143573382","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}