TH open : companion journal to thrombosis and haemostasis最新文献

{"title":"Compassionate Use of Osocimab in Preventing Thrombotic Complications Without Incremental Bleeding: A Case Report.","authors":"Jan Beyer-Westendorf, Katrin Weber, Falk Eckart, Martin W Laass, Ralf Knöfler, Kate Benson, László B Tankó, Martin Bornhäuser","doi":"10.1055/a-2577-4474","DOIUrl":"10.1055/a-2577-4474","url":null,"abstract":"<p><strong>Objective: </strong>To describe an innovative anticoagulation strategy in a 20-year-old woman with innate jejunal atresia and ultrashort bowel syndrome who was dependent on long-term parenteral nutrition and suffered from multiple venous thrombotic events and bleeding complications since infancy.</p><p><strong>Design: </strong>Single-patient case report.</p><p><strong>Setting: </strong>Dresden University Hospital, Dresden, Germany.</p><p><strong>Patient: </strong>Being fully CVC-dependent since birth, our patient repeatedly developed catheter-related thrombosis (CRT) since infancy and was treated with daily low-molecular-weight heparin injections for more than 15 years. Despite this, clotting, severe gastrointestinal bleeding, and osteoporosis remained a persistent problem, causing numerous hospitalizations over the years, significant developmental delays, and a decline in the patient's body mass index (BMI). A short period of rivaroxaban treatment had to be stopped owing to acute gastrointestinal bleeding. After the failure of all approved anticoagulant concepts, compassionate use access was granted to the investigational drug osocimab, a human monoclonal antibody inhibitor of factor XIa. Hereditary FXI deficiency as well as FXI inhibition in animal models have been shown to reduce arterial and venous thrombosis without increasing bleeding. Consistent with this, short-term osocimab treatment has shown clinical efficacy in preventing postoperative venous thromboembolism after knee replacement surgery and in reducing dialysis conduit clotting compared with placebo in patients undergoing hemodialysis, without increasing the rate of clinically relevant bleeding versus comparators. After initiating osocimab, the patient experienced no further clotting complications, and bleeding decreased in frequency and severity. The patient's BMI decline immediately stopped; her weight increased by over 10% in the subsequent 20 months, and menstruation started 3 months later without signs of menorrhagia. Now, with 2.5 years of uninterrupted exposure outside of a clinical trial, this patient has experienced the longest duration of factor XIa inhibition to date. She continues to receive osocimab under the compassionate use program and maintains a positive change in her well-being and quality of life.</p>","PeriodicalId":94220,"journal":{"name":"TH open : companion journal to thrombosis and haemostasis","volume":"9 ","pages":"a25774474"},"PeriodicalIF":0.0,"publicationDate":"2025-05-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12096935/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144129794","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Rapid Determination of Xa Inhibitor Activity in Blood Using a Microfluidic Device that Measures Platelet Deposition and Fibrin Generation Under Flow.","authors":"Jason M Rossi, Karen A Panckeri, Soumita Ghosh, Tilo Grosser, Adam Cuker, Scott L Diamond","doi":"10.1055/a-2547-5710","DOIUrl":"10.1055/a-2547-5710","url":null,"abstract":"<p><strong>Background: </strong>Patients taking direct oral anticoagulants (DOACs) often present complicated scenarios following major bleeding, stroke, or emergency surgery. Rapid whole blood assays of DOAC levels would aid clinical decisions such as the need for DOAC reversal.</p><p><strong>Methods: </strong>We developed a single-use, storage-stable, eight-channel microfluidic device to estimate factor Xa (FXa) inhibitor (apixaban or rivaroxaban) levels in venous thromboembolism or atrial fibrillation patients. The assay simultaneously measured whole blood clotting dynamics on collagen/tissue factor (TF; wall shear rate, 200 ^-1 ) under four ex vivo conditions: no-treatment control, high dose Factor Xa inhibition, low dose or high dose FXa reversal agent (andexanet alfa). Fibrin and platelet deposition dynamics were monitored via two-color epifluorescence microscopy. Plasma samples were also evaluated by LC-MS/MS for DOAC concentrations.</p><p><strong>Results: </strong>Experiments with healthy volunteer blood spiked with DOAC verified device performance (DOAC IC ₅₀ ∼120 nM) and confirmed that andexanet alfa added to healthy donor blood had no off-target effect on platelet or fibrin signal. Patient whole blood monitored for 15 to 25 minutes (17 minutes mean runtime) allowed calculation of functional DOAC concentrations ranging from 2 to 500 nM that correlated well with LC-MS/MS determination of apixaban or rivaroxaban (R ²  = 0.7 or 0.9, respectively). Platelet dysfunction was not observed in any patient on DOAC. For a threshold of 100 nM DOAC, the area under the curve (AUC) was found to be 0.881 for apixaban and 0.933 for rivaroxaban.</p><p><strong>Conclusion: </strong>Microfluidic testing of whole blood can provide a rapid estimate of DOAC levels over the on-therapy range.</p>","PeriodicalId":94220,"journal":{"name":"TH open : companion journal to thrombosis and haemostasis","volume":"9 ","pages":"a25475710"},"PeriodicalIF":0.0,"publicationDate":"2025-03-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11967380/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143782318","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Risk of First Venous Thrombosis by Comparing Different Thrombin Generation Assay Conditions: Results from the MEGA Case-control Study.","authors":"Kristien Winckers, Eugenia Biguzzi, Stella Thomassen, Alexandra Heinzmann, Frits R Rosendaal, Tilman M Hackeng, Astrid van Hylckama-Vlieg","doi":"10.1055/a-2534-6123","DOIUrl":"10.1055/a-2534-6123","url":null,"abstract":"<p><strong>Background: </strong>Hypercoagulability is a risk factor for venous thromboembolism (VTE). Thrombin generation (TG) is a global coagulation assay that measures an individual's clotting tendency. We hypothesise that slow-onset TG (achieved by using a low procoagulant stimulus or an inhibitor of coagulation) is the optimal responsive TG method for detecting hypercoagulability.This study aimed to compare different TG assay conditions with respect to VTE risk and assess the risk of the first VTE.</p><p><strong>Materials and methods: </strong>Basal TG at low tissue factor (TF) concentration and high TF concentration in the presence and absence of activated protein C (APC) were measured in plasma samples from 2,081 patients with first VTE and 2,908 healthy controls from the Multiple Environmental and Genetic Assessment of risk factors for venous thrombosis (MEGA) study. TG parameters and normalised activated protein C sensitivity ratio (nAPCsr) were categorised into quartiles as measured in the controls. We calculated odds ratios (ORs) with 95% confidence intervals (CIs) of the first VTE for different TG categories.</p><p><strong>Results: </strong>Under all assay conditions the thrombin peak height was associated with VTE risk: peak height of >75th percentile, at low TF OR 6.8 (95% CI 5.5-8.3), at high TF, OR 3.0 (95% CI 2.5-3.6), and at high TF + APC, OR 3.8 (95% CI 3.2-4.5), all compared with a peak height of <25th percentile obtained in controls. An increased nAPCsr (higher resistance to APC) was also associated with VTE risk, OR 3.4 (95% CI 2.8-4.1).</p><p><strong>Conclusion: </strong>Increased TG is associated with the risk of first VTE, particularly when triggered with a low procoagulant stimulus.</p>","PeriodicalId":94220,"journal":{"name":"TH open : companion journal to thrombosis and haemostasis","volume":"9 ","pages":"a25346123"},"PeriodicalIF":0.0,"publicationDate":"2025-03-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11924298/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143671954","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Problem Solved? An Individual Ratio between Point-of-Care and Venous International Normalized Ratio Values in Two Patients with Antiphospholipid Syndrome: Two Case Reports.","authors":"Bettina C Geertsema-Hoeve, Massimo Radin, Savino Sciascia, Rolf T Urbanus, Albert Huisman, Josine Borgsteede-de Wilde, Maarten Limper","doi":"10.1055/a-2542-5358","DOIUrl":"10.1055/a-2542-5358","url":null,"abstract":"<p><p>Antiphospholipid syndrome (APS) is a rare autoimmune disorder characterized by thromboembolic and obstetric complications in the presence of persistent antiphospholipid antibodies (aPL). Treatment aims to prevent recurrent thrombosis, primarily using anticoagulation therapy with vitamin K antagonists (VKA). Monitoring of VKA therapy relies on the International Normalized Ratio (INR), which can be assessed using point-of-care testing (POCT). However, in a subset of APS patients with a high-risk aPL profile, the POCT-INR is falsely elevated, which might lead to underdosing of VKA and subsequent high risk of recurrent thrombosis. This case report describes two female patients with triple-positive thrombotic APS receiving VKA therapy. Both patients underwent biweekly paired INR measurements via POCT-INR and venous INR methods. Despite significant discrepancies, a strong individual linear correlation was observed: <i>r</i>  = 0.77 (95% confidence interval [CI]: 0.54-0.99, <i>p</i>  < 0.001) and <i>r</i>  = 0.93 (95% CI: 0.88-0.97, <i>p</i>  < 0.001), respectively. These findings suggest that individualized correction factors could be developed to improve the accuracy of POCT-INR measurements, thereby optimizing VKA dosing in these patients.</p>","PeriodicalId":94220,"journal":{"name":"TH open : companion journal to thrombosis and haemostasis","volume":"9 ","pages":"a25425358"},"PeriodicalIF":0.0,"publicationDate":"2025-03-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11924302/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143671554","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Assessment of the Haemostatic Potential of Platelets Readied for Transfusion.","authors":"Unwana Emagha, Khawla Yousif, Michelle Duff, Edwina Geraghty, Janice O'Shaughnessy, Philip Murphy, Stefano Verardi, Stephen Marcella, Roy Bentley, Dermot Cox","doi":"10.1055/a-2525-6768","DOIUrl":"10.1055/a-2525-6768","url":null,"abstract":"","PeriodicalId":94220,"journal":{"name":"TH open : companion journal to thrombosis and haemostasis","volume":"9 ","pages":"a25256768"},"PeriodicalIF":0.0,"publicationDate":"2025-03-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11922168/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143665651","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Vascular Endothelial Growth Factor (VEGF) as a Biomarker for Cancer-Associated Venous Thrombosis: A Meta-analysis.","authors":"Alison M Brown, Sophie Nock, Kathryn Musgrave, Amanda J Unsworth","doi":"10.1055/a-2513-4381","DOIUrl":"https://doi.org/10.1055/a-2513-4381","url":null,"abstract":"<p><p>Cancer-associated thrombosis affects between 1 and 20% of all patients diagnosed with cancer and is associated with significant morbidity and a poorer prognosis. Risk assessment scores exist which include the measurement of biomarkers, and which aim to identify patients at a higher risk of developing thrombotic events, but these are poor predictors and rarely used in routine clinical practice. VEGF is a potent angiogenic factor, produced by tumour cells, and released by platelets and is essential for tumour growth and progression. It also plays a role in the promotion of thrombosis through platelet activation and adhesion, and by inducing the expression of tissue factor. Therefore, the potential of VEGF to be used as a biomarker to predict cancer-associated thrombosis requires further investigation. This study reviewed the published literature to determine whether circulating VEGF levels are associated with increased risk of venous thromboembolism in patients with cancer. PubMed and OVID databases were systematically searched according to PRISMA guidelines for relevant papers using the keywords \"cancer\" AND \"thrombosis\" AND \"VEGF\" up to July 2023. Inclusion and exclusion criteria were applied. Seven papers (1,528 participants) were identified and included in the meta-analysis, three of which (922 participants) measured VEGF before a thrombotic event, and the remaining four (606 participants) measured VEGF at the time of the thrombosis. Our results showed that although plasma and serum VEGF tended to be higher in those who subsequently developed thrombosis than those who did not (mean difference 70.2 pg/mL for serum, and 11.44 pg/mL for plasma VEGF, 95% CI -2.39-25.73, <i>p</i>  = 0.10), this was not found to be statistically significant. However, analysis of VEGF following blood sampling at the time of thrombosis showed a stronger statistically significant association between increased VEGF levels and presence of thrombosis (mean difference 117.02 pg/mL for serum, and 116.6 pg/mL for plasma VEGF, 95% CI 55.42-190.82, <i>p</i>  = 0.0004). Based on current studies, whilst it is increased at the time of thrombosis, VEGF is not effective as a predictive biomarker of CAT.</p>","PeriodicalId":94220,"journal":{"name":"TH open : companion journal to thrombosis and haemostasis","volume":"9 ","pages":"a25134381"},"PeriodicalIF":0.0,"publicationDate":"2025-02-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12020352/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144047141","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"TH Open-Editor's Highlights of 2024.","authors":"Rory R Koenen","doi":"10.1055/a-2513-4445","DOIUrl":"10.1055/a-2513-4445","url":null,"abstract":"","PeriodicalId":94220,"journal":{"name":"TH open : companion journal to thrombosis and haemostasis","volume":"9 ","pages":"a25134445"},"PeriodicalIF":0.0,"publicationDate":"2025-01-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11817918/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143416594","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Why Current Detection of Vascular Calcification Falls Short and How to Improve on It.","authors":"Anouk Gentier, Mueez Aizaz, Maurice Halder, Alexandru Florea, Ingrid Dijkgraaf, Felix M Mottaghy, Tilman Hackeng, M Eline Kooi","doi":"10.1055/a-2495-1444","DOIUrl":"10.1055/a-2495-1444","url":null,"abstract":"<p><p>Vascular calcification is a common phenomenon in various vascular diseases, where its presence heralds increased occurrence of adverse disease events, which invariably lead to increased morbidity and mortality in patients. Although the impact of calcification has become apparent, adequate and early detection of the most damaging form of early microcalcification is still in its infancy, preventing reliable identification of locations that would benefit from intervention. In this review, we will provide an overview of the current state-of-the-art noninvasive calcification imaging and its persisting limitations. We discuss promising approaches that may address these limitations in the future. In this context particular attention will be paid to imaging modalities such as CT, PET, and ultrasonography and molecular and cellular mechanisms and agents involved in physiological bone formation.</p>","PeriodicalId":94220,"journal":{"name":"TH open : companion journal to thrombosis and haemostasis","volume":"8 4","pages":"e340-e349"},"PeriodicalIF":0.0,"publicationDate":"2024-12-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11679638/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142904732","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Increased Platelet Adhesiveness in Patients with Venous Thromboembolic Disease.","authors":"Julia Martinez-Sanchez, Sergi Torramade-Moix, Ana Belén Moreno-Castaño, Dolors Llobet, Didac Jerez-Dolz, Pablo Sanchez, Marina Carrasco, Sergi Mojal, Carla Moret, Mercedes Camacho, José Manuel Soria, Marta Palomo, Laura Martin-Fernandez, Francisco Vidal, Gines Escolar, Maribel Diaz-Ricart, Juan Carlos Souto","doi":"10.1055/s-0044-1800798","DOIUrl":"https://doi.org/10.1055/s-0044-1800798","url":null,"abstract":"<p><p><b>Background</b>  Association between global platelet function and the risk of venous thromboembolic disease (VTE) has been proposed, though the mechanisms do not involve increased platelet aggregation. However, platelet adhesiveness has not been systematically explored in VTE patients. <b>Objectives</b>  To evaluate platelet adhesive functions in VTE patients. <b>Methods</b>  Platelet adhesion was evaluated by using whole blood samples from VTE patients, selected based on short closure times on the PFA-100 ( <i>n</i>  = 54), and matched healthy individuals ( <i>n</i>  = 57) in: (i) the PFA-100, (ii) a cone plate analyzer (CPA), on a plastic surface, (iii) microfluidic devices, with two- and three-dimensional evaluation, and (iv) membrane glycoprotein analysis. Intraplatelet signaling was evaluated in isolated collagen type I (Col-I) activated platelets and platelets adhered on Col-I or von Willebrand factor (VWF) coated coverslips under flow. VWF antigen and ADAMTS-13 activity were measured in plasma samples. <b>Results</b>  PFA-100 closure times remained significantly shorter in patients. The CPA test showed a significant increase in the platelet aggregates size when using blood from VTE patients. Platelet adhesion on Col-I revealed a higher area covered by platelets and increased aggregate volume when exposed to samples from VTE patients. Protein P-ZAP70/SYK72 showed a phosphorylation level significantly increased in patients' platelets. Plasma VWF was significantly elevated in VTE patients. <b>Conclusions</b>  Platelets from VTE patients exhibit a proadhesive phenotype under flow conditions potentially related to the shortened occlusion times with the PFA-100. This enhanced adhesiveness may be explained by higher intraplatelet ZAP70/SYK72 phosphorylation and increased plasma VWF in patients. Therefore, primary hemostasis plays a significant role in the pathophysiology of VTE.</p>","PeriodicalId":94220,"journal":{"name":"TH open : companion journal to thrombosis and haemostasis","volume":"8 4","pages":"e329-e339"},"PeriodicalIF":0.0,"publicationDate":"2024-11-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11608120/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142776054","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Management of Therapeutic-intensity Unfractionated Heparin: A Narrative Review on Critical Points.","authors":"Isabelle Gouin-Thibault, Alexandre Mansour, Michael Hardy, Pierre Guéret, Emmanuel de Maistre, Virginie Siguret, Adam Cuker, François Mullier, Thomas Lecompte","doi":"10.1055/a-2359-0987","DOIUrl":"https://doi.org/10.1055/a-2359-0987","url":null,"abstract":"<p><p>Nowadays, unfractionated heparin (UFH) use is limited to selected patient groups at high risk of both bleeding and thrombosis (patients in cardiac surgery, in intensive care unit, and patients with severe renal impairment), rendering its management extremely challenging, with many unresolved questions despite decades of use. In this narrative review, we revisit the fundamental concepts of therapeutic anticoagulation with UFH and address five key points, summarizing controversies underlying the use of UFH and discussing the few recent advances in the field: (1) laboratory tests for UFH monitoring have significant limitations; (2) therapeutic ranges are not well grounded; (3) the actual influence of antithrombin levels on UFH's anticoagulant activity is not well established; (4) the concept of UFH resistance lacks supporting data; (5) scarce data are available on UFH use beyond acute venous thromboembolism. We therefore identified key issues to be appropriately addressed in future clinical research: (1) while anti-Xa assays are often considered as the preferred option, we call for a vigorous action to improve understanding of the differences between types of anti-Xa assays and to solve the issue of the usefulness of added dextran; (2) therapeutic ranges for UFH, which were defined decades ago using reagents no longer available, have not been properly validated and need to be confirmed or reestablished; (3) UFH dose adjustment nomograms require full validation.</p>","PeriodicalId":94220,"journal":{"name":"TH open : companion journal to thrombosis and haemostasis","volume":"8 3","pages":"e297-e307"},"PeriodicalIF":0.0,"publicationDate":"2024-10-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11486528/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142484704","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}