Research and Practice in Thrombosis and Haemostasis最新文献

{"title":"No correlation between thrombin generation and emicizumab levels: implications for monitoring emicizumab therapy","authors":"Konrad van der Zwet ,&nbsp;Mark Roest ,&nbsp;Dana Huskens ,&nbsp;Roger E.G. Schutgens ,&nbsp;Lize F.D. van Vulpen ,&nbsp;Kathelijn Fischer ,&nbsp;Rolf T. Urbanus","doi":"10.1016/j.rpth.2024.102658","DOIUrl":"10.1016/j.rpth.2024.102658","url":null,"abstract":"<div><h3>Background</h3><div>Emicizumab, a bispecific antibody that mimics factor (F)VIII, has significantly improved hemophilia A management. Although emicizumab levels can be measured, tools for estimating the hemostatic efficacy of emicizumab are lacking. Thrombin generation (TG) assays can distinguish bleeding phenotypes in persons with hemophilia A on FVIII prophylaxis and may also be used during emicizumab therapy.</div></div><div><h3>Objectives</h3><div>To assess the association between TG parameters, emicizumab levels, and bleeding in patients on emicizumab therapy.</div></div><div><h3>Methods</h3><div>A single-center longitudinal cohort study was conducted, with samples collected during the steady-state phase of emicizumab therapy. TG was measured using tissue factor (TF; TF-TG, 1 pM) and FXIa (FXIa-TG, 200 pM). Emicizumab concentrations were determined with mass spectrometry. Only treated bleeds were recorded. Pearson correlations (rho, <em>r</em>) were reported.</div></div><div><h3>Results</h3><div>Eighty-five samples from 49 patients were analyzed during a median of 1 year of emicizumab therapy. Most bleeds were traumatic (97%; <em>n</em> = 30), whereas 1 bleed was spontaneous. At 12 months, TF-TG (<em>r</em> = 0.42) showed a borderline correlation, and FXIa-TG (<em>r</em> = 0.15) showed no correlation with emicizumab concentrations. Although FXIa-TG showed a 9% higher endogenous thrombin potential in patients with zero vs ≥1 treated bleed (endogenous thrombin potential: 957 vs 878 nM/min, <em>P</em> = .045), neither the FXIa-peak height nor TF-TG showed any association with traumatic bleeding.</div></div><div><h3>Conclusion</h3><div>TG parameters showed no clinically relevant correlations with emicizumab plasma concentrations, were not associated with traumatic bleeding, and showed considerable intrapatient variability. Therefore, TG was not considered useful for monitoring coagulation potential in patients on steady-state emicizumab prophylaxis.</div></div>","PeriodicalId":20893,"journal":{"name":"Research and Practice in Thrombosis and Haemostasis","volume":"9 1","pages":"Article 102658"},"PeriodicalIF":3.4,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11754509/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143029455","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A cell-based model to study mechanisms of endothelial-dependent thrombin generation in response to inflammation and its modulation by hydroxychloroquine","authors":"Deepa J. Arachchillage ,&nbsp;Golzar Mobayen ,&nbsp;Mike Laffan ,&nbsp;Anna M. Randi ,&nbsp;Josefin Ahnström ,&nbsp;Charis Pericleous","doi":"10.1016/j.rpth.2024.102665","DOIUrl":"10.1016/j.rpth.2024.102665","url":null,"abstract":"<div><h3>Background</h3><div>Inflammation is a driver of thrombosis, but the phenomenon of thromboinflammation has been defined only recently, bringing together the multiple pathways involved. <em>In vitro</em> models can support the development of new therapeutics targeting the endothelium and also assess the existing immunomodulatory drugs, such as hydroxychloroquine, in modulating the inflammation-driven endothelial prothrombotic phenotype.</div></div><div><h3>Objectives</h3><div>To develop a model for thrombin generation (TG) on the surface of human endothelial cells (ECs) to assess pro/antithrombotic properties in response to inflammation. Furthermore, to elucidate the mechanisms of TG regulation and its modulation by immunomodulatory therapies.</div></div><div><h3>Methods</h3><div>Cytokine-induced (tumor necrosis factor [TNF]-α, interleukin [IL]-1β, and interferon-γ) effects on ECs isolated from umbilical veins or human aortic tissue were assessed using calibrated automated thrombography in platelet-poor plasma. The expression of key coagulant and inflammatory regulators was measured at the mRNA level. Tissue factor (TF) protein levels were further assessed by flow cytometry.</div></div><div><h3>Results</h3><div>Endothelial stimulation with TNF-α or IL-1β caused ECs to trigger TG without the addition of exogenous TF, with higher TG observed after 6 hours of stimulation than 24 hours. IL-1β induced higher peak thrombin (170 ± 5.9 nM vs 115 ± 4.9 nM), endogenous thrombin potential (1632 ± 35 nM ∗ min vs 1370 ± 23 nM ∗ min) presented as mean ± SD, and TF expression (∼2.8-fold higher) compared with TNF-α at 6 hours. Interferon-γ stimulation failed to induce TG and TF expression. The immunomodulatory drug, hydroxychloroquine, reduced cytokine-induced TG and downregulated TF expression.</div></div><div><h3>Conclusion</h3><div>We provide detailed optimization of a robust <em>in vitro</em> model to assess the induction of an inflammation-driven endothelial prothrombotic phenotype that is also sensitive to immunomodulatory therapies, providing a tool for investigating mechanisms of disease and new drugs.</div></div>","PeriodicalId":20893,"journal":{"name":"Research and Practice in Thrombosis and Haemostasis","volume":"9 1","pages":"Article 102665"},"PeriodicalIF":3.4,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11772944/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143060628","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Carbon dioxide alleviates platelet storage lesions via stimulating fatty acid metabolism and reducing platelet glucose consumption","authors":"Shunli Gu,&nbsp;Jinmei Xu,&nbsp;Erxiong Liu,&nbsp;Xuejia Hou,&nbsp;Ning An,&nbsp;Yaozhen Chen,&nbsp;Zhixin Liu,&nbsp;Wenting Wang,&nbsp;Xingbin Hu,&nbsp;Wen Yin","doi":"10.1016/j.rpth.2025.102681","DOIUrl":"10.1016/j.rpth.2025.102681","url":null,"abstract":"<div><h3>Background</h3><div>The timely administration of platelet transfusions is critical for patient survival, and the clinical demand for platelet transfusions has been steadily increasing. However, platelet storage lesions (PSLs) that develop during <em>in vitro</em> preservation exacerbate these shortages. The PSL is significantly influenced by various factors, including temperature, gas composition, and buffering systems. Strategies to mitigate PSLs and improve platelet storage have been actively explored in recent years.</div></div><div><h3>Objectives</h3><div>This study aimed to investigate whether elevated carbon dioxide (CO₂) levels improve platelet quality and functionality during storage.</div></div><div><h3>Methods</h3><div>Platelet concentrates from 28 donors were stored under control or 3% CO₂ conditions at 22 ± 2 °C for up to 7 days. Platelet quality was evaluated through scanning electron microscopy, adhesion, aggregation, clot contraction, activation, apoptosis assays, blood gas, adenosine triphosphate, metabolomics analyses, and <em>in vivo</em> thrombosis and survival tests.</div></div><div><h3>Results</h3><div>Our findings indicate that increasing the CO₂ concentration in the storage environment mitigates PSLs and improves platelet quality.</div></div><div><h3>Conclusion</h3><div>Our study highlights the potential benefits of utilizing a high CO₂ storage environment to improve platelet preservation, offering a promising method to address clinical platelet shortages.</div></div>","PeriodicalId":20893,"journal":{"name":"Research and Practice in Thrombosis and Haemostasis","volume":"9 1","pages":"Article 102681"},"PeriodicalIF":3.4,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143387615","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Measurement of factor XIII for the diagnosis and management of deficiencies: insights from a retrospective review of 10 years of data on consecutive samples and patients","authors":"Mohammed Abdullah Al Sharif ,&nbsp;Natalie Mathews ,&nbsp;Subia Tasneem ,&nbsp;Karen A. Moffat ,&nbsp;Stephen A. Carlino ,&nbsp;Siraj Mithoowani ,&nbsp;Catherine P.M. Hayward","doi":"10.1016/j.rpth.2025.102689","DOIUrl":"10.1016/j.rpth.2025.102689","url":null,"abstract":"<div><h3>Background</h3><div>Factor XIII (FXIII) deficiency is a challenge in the diagnosis of rare bleeding disorders with inherited and acquired causes.</div></div><div><h3>Objectives</h3><div>We evaluated consecutive cases tested for FXIII deficiency for insights on diagnosis.</div></div><div><h3>Methods</h3><div>With ethics approval, we retrospectively reviewed FXIII tests performed between 2013 and 2023 and local patient records for insights into causes and presentations of FXIII deficiency.</div></div><div><h3>Results</h3><div>Two thousand one hundred ninety-one samples from 1915 patients (ages: 0-90 years; 38% local) were tested. The FXIII activity (FXIII:Act; Berichrom FXIII, Siemens Healthcare) was low in 14%/9.7% of tested samples/patients. FXIII subunit A antigen (FXIII-A:Ag; Werfen HemosIL FXIII antigen; low in 45% of 251 samples) helped characterize FXIII deficiency severity and identify type 2 deficiencies from acquired FXIII inhibitors. Urea clot solubility tests (18.2% requested without FXIII:Act) were largely noninformative as all abnormal samples (<em>n</em> = 7) had undetectable FXIII-A:Ag levels. Excluding FXIII inhibitor patients, FXIII:Act showed strong correlation with FXIII-A:Ag (<em>R</em>² = 0.84, <em>P</em> &lt; .001) and weak correlation with plasma fibrinogen (<em>R</em>² = .005, <em>P</em> &lt; .001). Some patients had combined acquired FXIII and fibrinogen deficiencies from consumption or major bleeding. FXIII-deficient and nondeficient patients had similar bleeding except for more umbilical and gastrointestinal bleeding among deficient patients (<em>P</em> &lt; .05). Most FXIII deficiencies were acquired (92%), and although several were autoimmune, most were from consumption, major bleeds, or severe infections or had uncertain significance, with bleeding sometimes attributable to other causes.</div></div><div><h3>Conclusion</h3><div>Congenital and acquired FXIII deficiency are associated with bleeding. Local practices were changed to ensure that FXIII:Act is used to screen for FXIII deficiency and that deficient patients have FXIII:Act and FXIII-A:Ag quantified and compared.</div></div>","PeriodicalId":20893,"journal":{"name":"Research and Practice in Thrombosis and Haemostasis","volume":"9 1","pages":"Article 102689"},"PeriodicalIF":3.4,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143387616","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Immune tolerance induction for inhibitor eradication in nonsevere hemophilia A: a case series","authors":"Sanober Nusrat ,&nbsp;Niveditha Popuri ,&nbsp;Vishnu Nagalapuram ,&nbsp;Osman Khan","doi":"10.1016/j.rpth.2024.102637","DOIUrl":"10.1016/j.rpth.2024.102637","url":null,"abstract":"<div><h3>Background</h3><div>Persons with hemophilia A are at risk of inhibitor development with repeated exposures to factor (F)VIII concentrates. When persons with nonsevere hemophilia A (NSHA) develop inhibitors, they are at risk of developing severe bleeding manifestations like persons with severe hemophilia A (SHA). Evidence to guide inhibitor eradication in this population is limited as opposed to persons with SHA who develop inhibitors. Hence, inhibitor eradication strategies in NSHA are based on observational and retrospective data and are largely adopted from evidence derived from SHA with inhibitors.</div></div><div><h3>Key Clinical Question</h3><div>Can immune tolerance induction be used for patients with NSHA who develop inhibitors?</div></div><div><h3>Clinical Approach</h3><div>In this case series, we describe our single institutional experience with the management of 5 persons with NSHA who developed FVIII inhibitors, leading to significant bleeding complications, and underwent successful immune tolerance induction with eradication of FVIII inhibitor.</div></div><div><h3>Conclusion</h3><div>More research specific to persons with NSHA with inhibitors is warranted to develop guidelines regarding indications and strategies for inhibitor eradication therapy.</div></div>","PeriodicalId":20893,"journal":{"name":"Research and Practice in Thrombosis and Haemostasis","volume":"9 1","pages":"Article 102637"},"PeriodicalIF":3.4,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11786646/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143080790","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Global prevalence of platelet-type von Willebrand disease","authors":"Omid Seidizadeh ,&nbsp;Andrea Cairo ,&nbsp;Maha Othman ,&nbsp;Flora Peyvandi","doi":"10.1016/j.rpth.2025.102682","DOIUrl":"10.1016/j.rpth.2025.102682","url":null,"abstract":"<div><h3>Background</h3><div>Platelet-type von Willebrand disease (PT-VWD) is a rare autosomal dominant disorder. It is caused by gain-of-function gene variants in the platelet <em>GP1BA</em>, which results in excessive binding between GPIbα and von Willebrand factor (VWF). The prevalence of PT-VWD is unknown.</div></div><div><h3>Objectives</h3><div>To establish the worldwide and within distinct ethnic groups prevalence of PT-VWD.</div></div><div><h3>Methods</h3><div>We used available exome and genome sequencing data of 807,162 (730,947 exomes and 76,215 genomes) subjects from the Genome Aggregation Database (gnomAD-v4.1).</div></div><div><h3>Results</h3><div>Among the 1,614,324 alleles analyzed in the gnomAD population, there were 1397 distinct <em>GP1BA</em> variants. Of them, 4 variants (p.Arg127Gln, p.Leu194Phe, p.Gly249Val, and p.Met255Ile) have been previously reported to cause PT-VWD. Considering these 4 known pathogenic variants, we estimated a global PT-VWD prevalence of 136 cases/10⁶. The highest estimated prevalence of PT-VWD was found in Africans/African Americans (160/10⁶), Finnish (156/10⁶), Europeans (149/10⁶), and South Asians (110/10⁶), followed by Ashkenazi Jewish (68/10⁶) and East Asian (45/10⁶) ethnicities. In the population with no assigned ethnicity, a prevalence of 126/10⁶ was estimated. Since no pathogenic <em>GP1BA</em> variants that were previously reported to cause PT-VWD were found in Admixed American and Middle Eastern ethnicities, we were unable to estimate the PT-VWD prevalence in these 2 populations. We found a global prevalence of 2.5/10⁶ for severe PT-VWD and 134/10⁶ for the mild form.</div></div><div><h3>Conclusion</h3><div>This population-based genetic epidemiology analysis indicates a substantially higher than expected frequency of PT-VWD. This novel finding suggests that a large number of PT-VWD patients are still under- or misdiagnosed.</div></div>","PeriodicalId":20893,"journal":{"name":"Research and Practice in Thrombosis and Haemostasis","volume":"9 1","pages":"Article 102682"},"PeriodicalIF":3.4,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143155814","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Anticoagulant management of cancer-associated thrombosis and thrombocytopenia: a retrospective chart review","authors":"Umaima Abbas ,&nbsp;Robin MacKenzie ,&nbsp;Ushra Khan ,&nbsp;Rija Fatima ,&nbsp;Tzu-Fei Wang ,&nbsp;Rong Luo ,&nbsp;Caroline Hamm ,&nbsp;Andrea Cervi","doi":"10.1016/j.rpth.2025.102684","DOIUrl":"10.1016/j.rpth.2025.102684","url":null,"abstract":"<div><h3>Background</h3><div>Patients with cancer-associated thrombosis (CAT) are at an increased risk of recurrent thrombosis and bleeding, especially if there is treatment- or disease-related thrombocytopenia. While direct oral anticoagulants (DOACs) are used in the management of CAT, low molecular weight heparin (LMWH) continues to be recommended for CAT with thrombocytopenia.</div></div><div><h3>Objectives</h3><div>This study aimed to identify the rates of recurrent venous thromboembolism (VTE) and bleeding in patients with CAT and thrombocytopenia treated with DOACs compared with LMWH.</div></div><div><h3>Methods</h3><div>A retrospective review of patients with CAT and thrombocytopenia (platelet count &lt;100,000/μL) was conducted. Primary outcomes included rates of recurrent VTE and major bleeding over 90 days.</div></div><div><h3>Results</h3><div>Forty-two patients met the inclusion criteria; 20 (47.6%) had a solid organ malignancy while 22 (52.4%) had a hematologic malignancy. Within the first 7 days of VTE, 3 (7.1%) patients had a platelet count &lt;25,000/μL, 9 (21.4%) had 25,000 to 50,000/μL, and 19 (45.2%) had 50,000 to 100,000/μL. Sixteen patients (38.1%) received a DOAC for initial treatment, while 19 (45.2%) received LMWH. Among patients treated with DOACs, there were no recurrent VTEs, 2 clinically relevant nonmajor bleeding events (12.5%) within the first 2 weeks, and 1 minor bleed (6.3%) in the second month, while those treated with LMWH had 1 recurrent VTE (5.3%) in the second month and 2 clinically relevant nonmajor bleeding events (10.5%) within the first 2 months.</div></div><div><h3>Conclusion</h3><div>Rates of thrombosis and major bleeding were similar among thrombocytopenic patients with CAT treated with DOACs and LMWH, although differences in baseline patient characteristics can be confounders. Further prospective research on the optimal anticoagulant management of CAT with thrombocytopenia is needed.</div></div>","PeriodicalId":20893,"journal":{"name":"Research and Practice in Thrombosis and Haemostasis","volume":"9 1","pages":"Article 102684"},"PeriodicalIF":3.4,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143156331","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Reduced- versus full-dose anticoagulants for the extended treatment of cancer-associated venous thromboembolism in Thai patients","authors":"Kawin Vichaidit,&nbsp;Pichika Chantrathammachart,&nbsp;Pimjai Niparuck,&nbsp;Teeraya Puawilai,&nbsp;Pantep Angchaisuksiri MD,&nbsp;Kochawan Boonyawat","doi":"10.1016/j.rpth.2024.102643","DOIUrl":"10.1016/j.rpth.2024.102643","url":null,"abstract":"<div><h3>Background</h3><div>Reduced-dose anticoagulant therapy for extended treatment of cancer-associated venous thromboembolism (VTE) has been used to avoid bleeding. However, it may increase the risk of recurrent VTE.</div></div><div><h3>Objectives</h3><div>To study the rate of recurrent VTE and bleeding complications in Thai patients with cancer-associated VTE who were treated with full-dos/e or reduced-dose anticoagulants.</div></div><div><h3>Methods</h3><div>A retrospective cohort study was conducted in a single-center academic hospital. Electronic medical records were reviewed from 2016-2023. Patients with cancer-associated VTE who received anticoagulants for at least 3 months were evaluated. Reduced-dose anticoagulant was defined as a dose that was lower than the recommended standard dosage. The primary outcome was recurrent VTE. The secondary outcomes were major bleeding and clinically relevant nonmajor bleeding.</div></div><div><h3>Results</h3><div>A total of 229 patients were included. The median age was 65 years (IQR, 54-72). In the reduced-dose group, age and history of previous bleeding were higher than in the full-dose group. There were 169 (74%) patients and 60 (26%) patients who received full- and reduced-dose anticoagulants. The median time to reduce the dose was 3.6 months (IQR, 0.7-5.5). Of a total of 7 (3.1%) recurrent VTEs, 4 (2.4%) occurred in the full-dose and 3 (5.0%) in the reduced-dose groups (<em>P</em> = .4), respectively. The median time to recurrent VTE was 7.2 months (IQR, 3.5-12.4). There were 8 (3.5%) bleeding events, 7 (4.1%) and 1 (1.7%) in the full and reduced-dose anticoagulant groups (<em>P</em> = .35), respectively. The median follow-up time was 1.5 years (IQR, 1-3.1).</div></div><div><h3>Conclusion</h3><div>Older age and a history of previous bleeding were associated with the use of reduced-dose anticoagulants. Patients with cancer-associated VTE receiving reduced-dose anticoagulants had a numerically higher risk of recurrent VTE and lower bleeding outcomes compared with those receiving full-dose anticoagulants.</div></div>","PeriodicalId":20893,"journal":{"name":"Research and Practice in Thrombosis and Haemostasis","volume":"9 1","pages":"Article 102643"},"PeriodicalIF":3.4,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11699720/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142932615","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Andexanet alfa: trials just leave us with more questions","authors":"Richard J. Buka","doi":"10.1016/j.rpth.2024.102628","DOIUrl":"10.1016/j.rpth.2024.102628","url":null,"abstract":"<div><div>Andexanet Alfa in Acute Intracranial Hemorrhage in Patients Receiving an Oral Factor Xa Inhibitor (ANNEXA-I), the first ever randomized controlled trial of a reversal agent for direct oral anticoagulants, was published in 2024. The trial, which randomized patients with intracranial hemorrhage to andexanet alfa or usual care, was mandated by the United States Food and Drug Administration as part of its conditional approval in 2018. This approval was originally based on the single-arm trial, The Andexanet Alfa, a Novel Antidote to the Anticoagulation Effects of Factor Xa Inhibitors (ANNEXA-4). ANNEXA-I was stopped early for benefit and showed a reduction in the number of patients with significant hematoma expansion. However, the study was not powered for clinical endpoints such as disability or death and showed no difference in these outcomes. It did, however, show an increased risk of thrombosis, predominantly stroke with andexanet alfa. In this perspective, I reflect on some of the key criticisms of the trial and the implications for its interpretation.</div></div>","PeriodicalId":20893,"journal":{"name":"Research and Practice in Thrombosis and Haemostasis","volume":"9 1","pages":"Article 102628"},"PeriodicalIF":3.4,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11760292/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143047731","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Transfusion in trauma: empiric or guided therapy?","authors":"Liam Barrett ,&nbsp;Nicola Curry","doi":"10.1016/j.rpth.2024.102663","DOIUrl":"10.1016/j.rpth.2024.102663","url":null,"abstract":"<div><div>A state of the art lecture titled “Transfusion therapy in trauma—what to give? Empiric vs guided” was presented at the International Society on Thrombosis and Haemostasis Congress in 2024. Uncontrolled bleeding is the commonest preventable cause of death after traumatic injury. Hemostatic resuscitation is the foundation of contemporary transfusion practice for traumatic bleeding and has 2 main aims: to immediately support the circulating blood volume and to treat/prevent the associated trauma-induced coagulopathy. There are 2 broad types of hemostatic resuscitation strategy: empiric ratio-based therapy, often using red blood cells and fresh frozen plasma in a 1:1 ratio, and targeted therapy where the use of platelets, plasma, or fibrinogen is guided by laboratory or viscoelastic hemostatic tests. There are benefits, and limitations, to each strategy and neither approach has yet been shown to improve outcomes across all patient groups. Questions remain, and future directions for improving transfusion therapy are likely to require novel approaches that have greater flexibility to evaluate and treat heterogeneous trauma cohorts. Such approaches may include the integration of machine learning technologies in clinical systems, with real-time linkage of clinical and laboratory data, to aid early recognition of patients at the greatest risk of bleeding and to direct and individualize transfusion therapies. Greater mechanistic understanding of the underlying pathobiology of trauma-induced coagulopathy and the direct effects of common treatments on this process will be of equal importance to the development of new treatments. Finally, we summarize relevant new data on this topic presented at the 2024 ISTH Congress.</div></div>","PeriodicalId":20893,"journal":{"name":"Research and Practice in Thrombosis and Haemostasis","volume":"9 1","pages":"Article 102663"},"PeriodicalIF":3.4,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11774821/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143067431","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}