Research and Practice in Thrombosis and Haemostasis最新文献

{"title":"Hemostatic conditions following autologous transfusion of fresh vs stored platelets in experimental endotoxemia: an open-label randomized controlled trial with healthy volunteers","authors":"Stefan F. van Wonderen ,&nbsp;Floor L.F. van Baarle ,&nbsp;Anita M. Tuip-de Boer ,&nbsp;Chantal A. Polet ,&nbsp;Robin van Bruggen ,&nbsp;Christie Vermeulen ,&nbsp;Thomas R.L. Klei ,&nbsp;Chi M. Hau ,&nbsp;Rienk Nieuwland ,&nbsp;Cornelis van ’t Veer ,&nbsp;Anna L. Peters ,&nbsp;Sanne de Bruin ,&nbsp;Alexander P.J. Vlaar ,&nbsp;Bart J. Biemond ,&nbsp;Marcella C.A. Müller","doi":"10.1016/j.rpth.2024.102612","DOIUrl":"10.1016/j.rpth.2024.102612","url":null,"abstract":"<div><h3>Background</h3><div>Platelet increment is reportedly lower for maximum stored platelet concentrates (PCs) and during pyrexia, and <em>in vitro</em> function differs between fresh and stored PCs. However, little is known about the function of fresh and stored platelets during inflammation.</div></div><div><h3>Objectives</h3><div>The aim was to study differences in hemostatic function after transfusion of fresh or stored PCs in a human model of experimental endotoxemia.</div></div><div><h3>Methods</h3><div>Thirty-six healthy male subjects received either 2 ng/kg lipopolysaccharide (LPS) or a control (physiological saline 0.9%) and were randomly assigned to subsequently receive an autologous transfusion of either fresh (2-days-old) or stored (7-days-old) platelets, or saline control. Extracellular vesicles (EVs) were determined using flow cytometry, thrombin–antithrombin complex (TATc) was assessed using enzyme-linked immunosorbent assay, and hemostatic function was assessed using rotational thromboelastometry (ROTEM).</div></div><div><h3>Results</h3><div>LPS infusion caused a marked increase in TATc, EVs and fibrinolysis. Thromboelastometry data revealed that following infusion of LPS, subjects exhibited in general a hypocoagulable state compared with those not receiving LPS. Platelet transfusions led to a reduced clotting time and an augmentation in clot strength, indicated by maximum clot firmness, solely among subjects undergoing endotoxemia. There were no significant differences in TATc or amount of EVs release after transfusion of fresh or stored platelets.</div></div><div><h3>Conclusion</h3><div>A significant increase in TATc and EVs as well as a difference in hemostatic function after endotoxemia were observed. During endotoxemia, platelet transfusion resulted in enhanced coagulation and hemostatic function; however, no substantial differences were observed between transfusion of fresh or stored PCs.</div></div>","PeriodicalId":20893,"journal":{"name":"Research and Practice in Thrombosis and Haemostasis","volume":"8 8","pages":"Article 102612"},"PeriodicalIF":3.4,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142702349","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":"Utilizing artificial intelligence for the detection of hemarthrosis in hemophilia using point-of-care ultrasonography","authors":"Pascal N. Tyrrell ,&nbsp;María Teresa Alvarez-Román ,&nbsp;Nihal Bakeer ,&nbsp;Brigitte Brand-Staufer ,&nbsp;Victor Jiménez-Yuste ,&nbsp;Susan Kras ,&nbsp;Carlo Martinoli ,&nbsp;Mauro Mendez ,&nbsp;Azusa Nagao ,&nbsp;Margareth Ozelo ,&nbsp;Janaina B.S. Ricciardi ,&nbsp;Marek Zak ,&nbsp;Johannes Roth","doi":"10.1016/j.rpth.2024.102602","DOIUrl":"10.1016/j.rpth.2024.102602","url":null,"abstract":"<div><h3>Background</h3><div>Recurrent hemarthrosis and resultant hemophilic arthropathy are significant causes of morbidity in persons with hemophilia, despite the marked evolution of hemophilia care. Prevention, timely diagnosis, and treatment of bleeding episodes are key. However, a physical examination or a patient’s assessment of musculoskeletal pain may not accurately identify a joint bleed. This difficulty is compounded as hemophilic arthropathy progresses.</div></div><div><h3>Objectives</h3><div>Our system aims to utilize artificial intelligence and ultrasonography (US; point-of-care and handheld) to enable providers, and ultimately patients, to detect joint bleeds at the bedside and at home. We aimed to develop and assess the reliability of artificial intelligence algorithms in detecting and segmenting synovial recess distension (SRD; an indicator of disease activity) on US images of adult and pediatric knee, elbow, and ankle joints.</div></div><div><h3>Methods</h3><div>A total of 12,145 joint exams, comprising 61,501 US images from 7 international healthcare centers, were collected. The dataset included healthy participants and adult and pediatric persons with hemophilia, with and without SRD. Images were manually labeled by 2 experts and used to train binary convolutional neural network classifiers and segmentation models. Metrics to evaluate performance included accuracy, sensitivity, specificity, and area under the curve.</div></div><div><h3>Results</h3><div>The algorithms exhibited high performance across all joints and all cohorts. Specifically, the knee model showed an accuracy of 97%, sensitivity of 96%, specificity of 97%, and an area under the curve of 0.97 in SRD. High Dice coefficients (80%-85%) were achieved in segmentation tasks across all joints.</div></div><div><h3>Conclusion</h3><div>This technology could assist with the early detection and management of hemarthrosis in hemophilia.</div></div>","PeriodicalId":20893,"journal":{"name":"Research and Practice in Thrombosis and Haemostasis","volume":"8 8","pages":"Article 102602"},"PeriodicalIF":3.4,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142723701","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":"Impact of self-reported race on Villalta Scale postthrombotic syndrome scores and correlation with venous disease-specific quality of life: an exploratory analysis of the Acute Venous Thrombosis: Thrombus Removal with Adjunctive Catheter-Directed Thrombolysis Trial","authors":"James Shih MD ,&nbsp;Chu-Shu Gu PhD ,&nbsp;Suresh Vedantham MD ,&nbsp;John Kaufman MD ,&nbsp;Susan R. Kahn MD","doi":"10.1016/j.rpth.2024.102609","DOIUrl":"10.1016/j.rpth.2024.102609","url":null,"abstract":"<div><h3>Background</h3><div>The Villalta Scale (VS) to diagnose postthrombotic syndrome (PTS) consists of 5 patient-reported leg symptoms and 6 clinician-rated leg signs. It is unknown how the scale performs across racial groups.</div></div><div><h3>Objectives</h3><div>Our study explored if there were differences in VS scores, particularly clinician-rated signs components, according to self-reported race.</div></div><div><h3>Methods</h3><div>Exploratory analysis of the ATTRACT trial, a randomized controlled trial conducted at 56 US sites that investigated pharmacomechanical catheter-directed thrombolysis to prevent PTS after proximal deep vein thrombosis (DVT). At the 6-month visit after randomization, we compared self-reported Black (n = 123) and White (n = 541) participants for mean total VS score, VS symptoms score, VS signs score, individual signs scores, and correlation coefficients between VS signs and VS symptoms scores and between VS signs and Venous Insufficiency Epidemiological and Economic Study Quality of Life (VEINES-QOL) scores (a self-reported venous disease-specific quality of life measure).</div></div><div><h3>Results</h3><div>Mean total VS score (4.67 vs. 4.12, <em>P</em> = .54),VS signs score (1.66 vs. 2.00, <em>P</em> = .07), and VS symptoms score (2.83 vs. 2.04, <em>P</em> = .10) were similar between Black and White participants. The mean score for one individual VS sign, venous ectasia, was lower in Black vs. White participants (0.24 vs. 0.63, <em>P</em>&lt; .01). There was similar, modest correlation in Black and White participants between VS signs and VS symptoms scores (<em>r</em>_black = 0.19; <em>r</em>_white = 0.23) and between VS signs and VEINES-QOL scores (<em>r</em>_black = −0.32; <em>r</em>_white = −0.30). Results were adjusted for ATTRACT trial treatment group, age, sex, body mass index, DVT extent, hypertension, diabetes, dyslipidemia, and congestive heart failure.</div></div><div><h3>Conclusion</h3><div>The findings suggest that some differences in VS scores exist according to self-reported race. It is unclear whether these reflect clinicians’ underrating of some VS signs and/or differences in PTS severity. Further work is needed to understand how the VS performs across racial groups.</div></div>","PeriodicalId":20893,"journal":{"name":"Research and Practice in Thrombosis and Haemostasis","volume":"8 8","pages":"Article 102609"},"PeriodicalIF":3.4,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142702286","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":"Inhibitor development upon switching from plasma-derived to recombinant factor VIII in previously untreated patients with severe hemophilia A: the PUP-SWITCH study","authors":"Syna Miri ,&nbsp;Frits R. Rosendaal ,&nbsp;Kaan Kavakli ,&nbsp;Peyman Eshghi ,&nbsp;Soha Mohammadi Moghaddam ,&nbsp;Sara Scardo ,&nbsp;Behnaz Habibpanah ,&nbsp;Mohsen Elalfy ,&nbsp;Susan Halimeh ,&nbsp;Gabriella Nicolò ,&nbsp;Dilek Gökçebay ,&nbsp;Namık Özbek ,&nbsp;Tiraje Celkan ,&nbsp;Ahmad Mohammadi ,&nbsp;Mehran Karimi ,&nbsp;Amin Shahsavani ,&nbsp;Bariş Yılmaz ,&nbsp;Canan Albayrak ,&nbsp;Burcak Gunes ,&nbsp;Zühre Kaya ,&nbsp;Flora Peyvandi","doi":"10.1016/j.rpth.2024.102595","DOIUrl":"10.1016/j.rpth.2024.102595","url":null,"abstract":"<div><h3>Background</h3><div>The SIPPET randomized clinical trial showed that in previously untreated patients (PUPs) with severe hemophilia A, treatment with plasma-derived factor (F)VIII (pdFVIII) within the first 50 exposure days (EDs) was associated with a lower cumulative incidence of inhibitors than with recombinant FVIII (rFVIII). Switching to rFVIII beyond 50 EDs with pdFVIII is a treatment often implemented by many centers. The question is whether or not this switch may induce a risk of inhibitor development.</div></div><div><h3>Objectives</h3><div>We investigated if in PUPs with severe hemophilia A switched after 50 EDs from pdFVIII to rFVIII, a novel inhibitor peak appears.</div></div><div><h3>Methods</h3><div>The PUP-SWITCH observational retrospective study was designed to investigate the cumulative incidence of novel inhibitors after switching PUPs to rFVIII after 50 and before 150 EDs. Hemophilia centers that routinely switched PUPs from pdFVIII to rFVIII within this exposure time frame were invited to participate. Patients were followed up for at least 50 EDs after the switch.</div></div><div><h3>Results</h3><div>Ninety-seven patients were evaluated, and 87 were included according to eligibility criteria between 2020 and 2022. Only one of them developed an inhibitor 20 EDs after switching, so the cumulative incidence was 1.15% (95% CI, 0.03%-6.24%).</div></div><div><h3>Conclusion</h3><div>PUP-SWITCH, a study focusing on PUPs undergoing a product class switch from pdFVIII to rFVIII after 50 EDs, showed that switching appears to be safe pertaining to the risk of development of new inhibitors.</div></div>","PeriodicalId":20893,"journal":{"name":"Research and Practice in Thrombosis and Haemostasis","volume":"8 8","pages":"Article 102595"},"PeriodicalIF":3.4,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142702288","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":"Outcomes of patients with acute pulmonary embolism managed in-house vs those transferred between hospitals: a retrospective observational study","authors":"Priyanka Sridhar ,&nbsp;Hong Yu Wang ,&nbsp;Agostina Velo ,&nbsp;Destiny Nguyen ,&nbsp;Avinash Singh ,&nbsp;Abdul Rehman ,&nbsp;Jason Filopei ,&nbsp;Madeline Ehrlich ,&nbsp;Robert Lookstein ,&nbsp;David J. Steiger","doi":"10.1016/j.rpth.2024.102606","DOIUrl":"10.1016/j.rpth.2024.102606","url":null,"abstract":"<div><h3>Background</h3><div>Interhospital transfer (IHT) for acute pulmonary embolism (PE) is increasingly performed to improve access to advanced reperfusion therapies. It is unclear if outcomes of patients undergoing IHT are comparable with those of patients presenting in-house to hospitals with PE Response Team (PERT) capabilities.</div></div><div><h3>Objectives</h3><div>To determine whether outcomes of patients with acute PE undergoing IHT differ from those of patients presenting in-house.</div></div><div><h3>Methods</h3><div>We retrospectively reviewed 386 patients with acute PE who were treated by PERT at 1 of 3 urban teaching hospitals in the Mount Sinai Health System in New York City from January 2021 to October 2023. Propensity score–weighted analysis was performed to compare the outcomes of patients managed in-house with those of patients undergoing IHT.</div></div><div><h3>Results</h3><div>Two hundred eighty-four patients presented in-house, while 102 were transferred from other hospitals. Median PE Severity Index score was 84, and 3 (0.8%), 80 (20.7%), 237 (61.4%), and 66 (17.1%) had low-risk, intermediate low–risk, intermediate high–risk, and high-risk PE. Odds of receiving systemic thrombolysis (odds ratio [OR], 1.06; <em>P</em> = .06) or advanced therapies (OR, 0.95; <em>P</em> = .003) were not significantly different between the 2 groups. Rates of 30-day mortality, major bleeding, and readmission were 6.9%, 2.9%, and 9.8% for the IHT group and 10.6%, 2.1%, and 13% for the in-house group, respectively. IHT patients had lower odds of 30-day mortality (OR, 0.88; <em>P</em> = .003) and higher odds of major bleeding (OR, 1.03; <em>P</em> = .04).</div></div><div><h3>Conclusion</h3><div>PERT-guided IHT for patients with acute PE was associated with reduced mortality but increased risk of bleeding compared with patients managed in-house at hospitals with PERT capabilities.</div></div>","PeriodicalId":20893,"journal":{"name":"Research and Practice in Thrombosis and Haemostasis","volume":"8 8","pages":"Article 102606"},"PeriodicalIF":3.4,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142748723","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":"Nonneutralizing antibodies in Nordic persons with moderate hemophilia A and B (the MoHem study)","authors":"Ragnhild J. Måseide MD, PhD ,&nbsp;Erik Berntorp MD, PhD ,&nbsp;Jan Astermark MD, PhD ,&nbsp;Anna Olsson MD, PhD ,&nbsp;Maria Bruzelius MD, PhD ,&nbsp;Tony Frisk MD, PhD ,&nbsp;Vuokko Nummi MD, PhD ,&nbsp;Riitta Lassila MD, PhD ,&nbsp;Karin Strandberg MD, PhD ,&nbsp;Geir E. Tjønnfjord MD, PhD ,&nbsp;Pål A. Holme MD, PhD","doi":"10.1016/j.rpth.2024.102611","DOIUrl":"10.1016/j.rpth.2024.102611","url":null,"abstract":"<div><h3>Background</h3><div>The impact of nonneutralizing antibodies (NNAs) in moderate hemophilia is elusive.</div></div><div><h3>Objectives</h3><div>To explore the presence of NNAs in Nordic persons with moderate hemophilia A (MHA) and B (MHB) in relation to treatment modality, clinical outcome, history of inhibitor, and the corresponding factor VIII (FVIII)/factor IX (FIX) gene mutation.</div></div><div><h3>Methods</h3><div>A cross-sectional multicenter study covering persons with MHA and MHB in Sweden, Finland, and Norway. Inhibitors were analyzed with the Bethesda assay, and NNAs were detected by enzyme-linked immunosorbent assay.</div></div><div><h3>Results</h3><div>Plasma samples from 137 MoHem study participants (median age 29 years; Q1-Q3, 15-54) were analyzed. NNAs were present in 11 of 82 (13%) of people with MHA and 7 of 55 (13%) of those with MHB irrespective of prophylactic or on-demand treatment, most frequently after 150 exposure days (EDs). Three NNA positive patients had a history of high-titer inhibitor, but current analyses were negative (&lt;0.6 BU/mL). Baseline FVIII/FIX activity was similar among NNA positive and negative patients. Current bleeding rates were low, but patients with NNAs captured a higher Hemophilia Joint Health Score (7 [median]; Q1-Q3, 3-20 vs. 4; 1-9) (<em>P</em> = .02) and had more frequently undergone arthroplasty or arthrodesis (5 [33%] vs. 15 [13%]) (<em>P</em> = .03).</div></div><div><h3>Conclusion</h3><div>NNAs were detected in 13% of Nordic persons with MHA and MHB, most frequently after 150 EDs. Patients with NNAs had more severe hemophilic arthropathy than patients without NNAs. The relationship between NNAs and clinical outcome in hemophilia should be further explored in a large cohort including pharmacokinetics and longitudinal observations with repeated blood sampling.</div></div>","PeriodicalId":20893,"journal":{"name":"Research and Practice in Thrombosis and Haemostasis","volume":"8 8","pages":"Article 102611"},"PeriodicalIF":3.4,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142702285","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":"The anticoagulant effects of milvexian, a novel small molecule factor XIa inhibitor, are neutralized by activated prothrombin complex concentrates and recombinant factor VIIa in human plasma and whole blood in vitro","authors":"Matthew Bunce,&nbsp;Zheng Huang Devine,&nbsp;Madhu Chintala","doi":"10.1016/j.rpth.2024.102600","DOIUrl":"10.1016/j.rpth.2024.102600","url":null,"abstract":"<div><h3>Background</h3><div>The development of anticoagulants that provide antithrombotic efficacy without a concomitant bleeding risk remains an unmet clinical need in thrombosis. Although direct oral anticoagulants (DOACs) have a reduced incidence of major bleeding compared with warfarin, they still carry a bleeding risk, resulting in a suboptimal therapeutic index. Epidemiologic data suggest that inhibiting activated factor XI (FXIa) may offer an improved safety profile with respect to bleeding risk compared with current-generation DOACs. Additionally, a phase II trial of milvexian in patients undergoing elective total knee replacement demonstrated robust dose-dependent efficacy with no statistically significant increase in bleeding. Nevertheless, the ability to rapidly and effectively correct FXIa inhibitor–induced anticoagulation may still be important in situations where patients experience uncontrolled bleeding or require emergency surgery.</div></div><div><h3>Objectives</h3><div>We assessed the ability to normalize the anticoagulant effects of the novel small-molecule FXIa inhibitor milvexian (BMS-986177/JNJ-70033093) <em>in vitro</em> using commercially available prohemostatic agents.</div></div><div><h3>Methods</h3><div>Milvexian-associated anticoagulation and correction was evaluated in activated partial thromboplastin time clotting assays, thromboelastography, and kaolin-initiated thrombin generation assays.</div></div><div><h3>Results</h3><div>Activated prothrombin complex concentrates (PCCs) and recombinant factor (rF)VIIa corrected the anticoagulant effects of milvexian in activated partial thromboplastin time clotting assays, thromboelastography, and kaolin-initiated thrombin generation assays. In contrast, other agents, including PCCs, rFIX, and rFVIII, demonstrated either modest or no correction of milvexian-associated anticoagulation.</div></div><div><h3>Conclusion</h3><div>This study demonstrated that currently available activated PCCs and rFVIIa normalize the anticoagulation induced by milvexian <em>in vitro</em>. The clinical utility of these agents remains to be established.</div></div>","PeriodicalId":20893,"journal":{"name":"Research and Practice in Thrombosis and Haemostasis","volume":"8 8","pages":"Article 102600"},"PeriodicalIF":3.4,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142748651","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":"Bleeding disorder of unknown cause: an illustrated review on current practice, knowledge gaps, and future perspectives","authors":"Amaury L.L. Monard ,&nbsp;Caroline M.A. Mussert ,&nbsp;Tirsa T. van Duijl ,&nbsp;Marieke J.H.A. Kruip ,&nbsp;Yvonne M.C. Henskens ,&nbsp;Maartje van den Biggelaar ,&nbsp;Roger E.G. Schutgens ,&nbsp;Saskia E.M. Schols ,&nbsp;Karin J. Fijnvandraat ,&nbsp;Karina Meijer ,&nbsp;Paul L. den Exter ,&nbsp;Laurens Nieuwenhuizen ,&nbsp;Iris van Moort ,&nbsp;Ross I. Baker ,&nbsp;James S. O’Donnell ,&nbsp;Marjon H. Cnossen ,&nbsp;Floor C.J.I. Heubel-Moenen ,&nbsp;BDUC-iN Study group","doi":"10.1016/j.rpth.2024.102625","DOIUrl":"10.1016/j.rpth.2024.102625","url":null,"abstract":"<div><div>In more than half of the individuals with a clinically relevant bleeding tendency who are referred to hemostasis experts, no biological etiology can be found after extensive laboratory testing. These persons are diagnosed with an unexplained bleeding tendency or “bleeding disorder of unknown cause” (BDUC). The mucocutaneous bleeding phenotype of individuals with BDUC is generally comparable to that of individuals with inherited bleeding disorders such as von Willebrand disease or platelet function disorders. BDUC definitions applied in literature are heterogeneous, but all comprise 2 main criteria: (1) there is an increased bleeding tendency based on the clinical view of the physician and/or an increased bleeding score; (2) no abnormalities are found with available hemostasis laboratory tests. This is reflected in the recent published BDUC definition by the Scientific and Standardization Committee of the International Society on Thrombosis and Haemostasis, stating that BDUC is a diagnosis of exclusion, characterized by normal hemostatic investigations despite a clinically significant bleeding tendency. Importantly, other nonhemostatic and acquired causes of bleeding should be excluded, but details on exclusion criteria and associated diagnostic testing remain undefined. Patients and health care providers are challenged by the uncertainty and lack of formal diagnosis particularly as there is no clear consensus regarding treatment. Research on the diagnostic value of new laboratory tests in individuals with BDUC has not yet been productive. In this illustrative review, the current practice and knowledge gaps in BDUC are addressed, previous research on BDUC is outlined and future directions with outstanding questions for future research in BDUC are highlighted.</div></div>","PeriodicalId":20893,"journal":{"name":"Research and Practice in Thrombosis and Haemostasis","volume":"8 8","pages":"Article 102625"},"PeriodicalIF":3.4,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142748647","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":"External validation of the Leiden Thrombosis Recurrence Risk Prediction models (L-TRRiP) for the prediction of recurrence after a first venous thrombosis in the Heart and Vascular Health study","authors":"J. Louise I. Burggraaf-van Delft ,&nbsp;Kerri L. Wiggins ,&nbsp;Nienke van Rein ,&nbsp;Saskia le Cessie ,&nbsp;Nicholas L. Smith ,&nbsp;Suzanne C. Cannegieter","doi":"10.1016/j.rpth.2024.102610","DOIUrl":"10.1016/j.rpth.2024.102610","url":null,"abstract":"<div><h3>Background</h3><div>Long-term outcome after a first venous thromboembolism (VTE) might be optimized by tailoring anticoagulant treatment duration on individual risks of recurrence and major bleeding. The L-TRRiP models (A–D) were previously developed in data from the Dutch Multiple Environment and Genetic Assessment of Risk Factors for Venous thrombosis study to predict VTE recurrence.</div></div><div><h3>Objectives</h3><div>We aimed to externally validate models C and D using data from the United States Heart and Vascular Health (HVH) study.</div></div><div><h3>Methods</h3><div>Data from participants with a first VTE who discontinued initial anticoagulant therapy were used to determine model performance. Missing data were imputed, and results were pooled according to Rubin’s rules. To determine discrimination, Harrell’s C-statistic was calculated. To assess calibration, the observed/expected (O/E) ratio was estimated, and calibration plots were created, in which we accounted for the competing risk of death. A stratified analysis based on age &lt;70 or &gt;70 years was performed.</div></div><div><h3>Results</h3><div>Of 1430 participants from the HVH study, 187 experienced an unprovoked VTE recurrence during follow-up. The C-statistics of L-TRRIP models C and D were 0.62 (95% CI, 0.56-0.67) and 0.61 (95% CI, 0.55-0.67), respectively. The O/E ratio (1.00; 95% CI, 0.84-1.17 and 1.09; 95% CI, 0.91-1.27, respectively) and calibration plots indicated good calibration. The discrimination was similar between participants &lt;70 or &gt;70 years, whereas overall calibration was lower in participants &lt;70 years.</div></div><div><h3>Conclusion</h3><div>The L-TRRiP models showed moderate discrimination and good calibration in a different population and can be used to guide clinical decision making. To assess the added value in daily clinical practice, a management study is needed.</div></div>","PeriodicalId":20893,"journal":{"name":"Research and Practice in Thrombosis and Haemostasis","volume":"8 8","pages":"Article 102610"},"PeriodicalIF":3.4,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142702287","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":"In-depth characterization of N-glycosylation and sialic acid content in fetal and adult fibrinogen","authors":"Tana V. Palomino ,&nbsp;Anastasia Sheridan ,&nbsp;David C. Muddiman ,&nbsp;Ashley C. Brown","doi":"10.1016/j.rpth.2024.102618","DOIUrl":"10.1016/j.rpth.2024.102618","url":null,"abstract":"<div><h3>Background</h3><div>Fetal fibrinogen is a variant present in neonates. Blood products used in neonates are tailored for adults and do not seamlessly integrate into neonatal clots. Increased sialic acid content has been found in fetal fibrinogen compared with adult fibrinogen. However, the extent or location of sialic acids on fibrinogen remains unknown.</div></div><div><h3>Objectives</h3><div>To investigate differences in glycosylation and sialic acid content between fetal and adult fibrinogen.</div></div><div><h3>Methods</h3><div>Glycans were eluted from human cord blood-isolated fetal fibrinogen and commercially available adult fibrinogen using filter-aided <em>N</em>-linked glycan separation. A <span><math><mrow><mi>α</mi></mrow></math></span>, B <span><math><mrow><mi>β</mi></mrow></math></span>, and <span><math><mrow><mi>λ</mi></mrow></math></span> chains were isolated using sodium dodecyl sulfate-polyacrylamide gel electrophoresis, and in-gel enzymatic digestion was performed. Infrared matrix-assisted laser desorption electrospray ionization mass spectrometry was used for analysis.</div></div><div><h3>Results</h3><div>In total, 39 and 22 glycans were detected in fetal and adult fibrinogen, respectively. Fetal fibrinogen glycans were most abundant in the lower molecular weight range &lt;4 kDa. After isolating the Aα, Bβ, and λ chains, increased glycosylation and sialic acid content was found in fetal fibrinogen. Increased glycosylation was detected across all 3 chains, and increased sialic acid content was found in the Bβ chain.</div></div><div><h3>Conclusion</h3><div>Sialylation in the Bβ chain of fetal fibrinogen supports previous findings showing more knob ‘B’ interactions occur in fetal fibrinogen than in adult fibrinogen during clot polymerization. This is also the first detection of glycosylation in the Aα chain of fibrinogen. By elucidating the fibrinogen <em>N</em>-linked glycome, this study found where sialic acid content differs the most between adult and fetal fibrinogen. This can ultimately be used to develop blood products that are neonatal-compatible.</div></div>","PeriodicalId":20893,"journal":{"name":"Research and Practice in Thrombosis and Haemostasis","volume":"8 8","pages":"Article 102618"},"PeriodicalIF":3.4,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142748652","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}