Background and objectives: Initial thrombin (FIIa) generated via the tissue factor (TF) pathway plays a crucial role in amplifying coagulation. There is growing evidence that the TF pathway might contribute to hypercoagulation in obesity. However, it is unclear if the initial generation of FIIa (TG) is associated with hypercoagulation in obesity, due to the lack of appropriate assays. This study aims to evaluate association between TF pathway-driven initial TG and hypercoagulability in obesity.
Methods: We measured the initial TG levels in plasma from male Tsumura Suzuki obese diabetes (TSOD) mice and overweight subjects using the highly sensitive TG assay. To induce initial TG, TF was added to the plasma and incubated at 37 °C for up to 3 min. After quenching the TG, we quantified the generated FIIa by kinetically monitoring its amidolytic activity with a fluorogenic substrate.
Results and conclusions: We observed that initial TG levels were significantly higher in TSOD mice (n=31) compared to non-obese mice (n=32). Even in the absence of exogenous TF, initial TG levels in obese mice and overweight individuals were elevated when procoagulant phospholipids were added alone. Moreover, the increased initial TG that the inhibitory anti-TF antibody abolished was detectable in reconstituted plasma including pellets prepared by high-speed centrifugation of plasma from obese mice, not in plasma supernatant. We attributed the promotion of the initial TG to the increase in procoagulant TF-bearing microvesicles in circulation. Based on the findings, measuring TF pathway-driven initial TG could be a valuable method for assessing hypercoagulability in obesity.
{"title":"Tissue Factor Pathway-Driven Initial Thrombin Generation is Associated with Hypercoagulability in Obesity.","authors":"Yuichi Kamikubo, Satomi Nagaya, Rina Inoue, Koichi Yamaguchi, Riyo Morimoto-Kamata, Eriko Morishita, Fahumiya Samad, Naoki Ohkura, Kenichi Inoue","doi":"10.1055/a-2552-2050","DOIUrl":"https://doi.org/10.1055/a-2552-2050","url":null,"abstract":"<p><strong>Background and objectives: </strong>Initial thrombin (FIIa) generated via the tissue factor (TF) pathway plays a crucial role in amplifying coagulation. There is growing evidence that the TF pathway might contribute to hypercoagulation in obesity. However, it is unclear if the initial generation of FIIa (TG) is associated with hypercoagulation in obesity, due to the lack of appropriate assays. This study aims to evaluate association between TF pathway-driven initial TG and hypercoagulability in obesity.</p><p><strong>Methods: </strong>We measured the initial TG levels in plasma from male Tsumura Suzuki obese diabetes (TSOD) mice and overweight subjects using the highly sensitive TG assay. To induce initial TG, TF was added to the plasma and incubated at 37 °C for up to 3 min. After quenching the TG, we quantified the generated FIIa by kinetically monitoring its amidolytic activity with a fluorogenic substrate.</p><p><strong>Results and conclusions: </strong>We observed that initial TG levels were significantly higher in TSOD mice (n=31) compared to non-obese mice (n=32). Even in the absence of exogenous TF, initial TG levels in obese mice and overweight individuals were elevated when procoagulant phospholipids were added alone. Moreover, the increased initial TG that the inhibitory anti-TF antibody abolished was detectable in reconstituted plasma including pellets prepared by high-speed centrifugation of plasma from obese mice, not in plasma supernatant. We attributed the promotion of the initial TG to the increase in procoagulant TF-bearing microvesicles in circulation. Based on the findings, measuring TF pathway-driven initial TG could be a valuable method for assessing hypercoagulability in obesity.</p>","PeriodicalId":23036,"journal":{"name":"Thrombosis and haemostasis","volume":" ","pages":""},"PeriodicalIF":5.0,"publicationDate":"2025-03-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143573753","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}
Stefan Loroch, Eleftherios Panagiotidis, Kristoffer Klewe, Frauke Swieringa, Johan W M Heemskerk, Jan-Paul Lerch, Andreas Greinacher, Ulrich Walter, Kerstin Jurk, Tobias John, Katalin Barkovits, Thomas Dandekar, Katrin Marcus, Johannes Balkenhol
Comprehensive characterization of platelets requires various functional assays and analytical techniques, including omics disciplines, each demanding a separate aliquot of the given sample. Consequently, sample material for each assay is often highly limited, necessitating the downscaling of methods to work with just a few micrograms of platelet protein.Here, we present a novel sample preparation platform for proteomics analysis using only 3 μg of purified platelet protein, corresponding to 2 × 106 platelets, which can be obtained from approximately 2 to 8 μL of blood from a healthy individual (1.5 × 105-4.5 × 105 platelets/μL) or approximately 100 μL of blood from a patient with severe thrombocytopenia (<2 × 104 platelets/µL).Using this platform, we detected a significant fraction of key players in the platelet activation cascade and, most importantly, identified 36 clinically relevant platelet disease markers even with a non-state-of-the art instrument. This makes LC-MS-based proteomics a highly attractive alternative to conventional assays, which often require milliliters of blood. Our platform transitions from our previously established 96-well proteomics workflow (PF96), which has been successfully employed in numerous platelet proteomics studies, into the 384-well format. This transition is accompanied by (1) a more than two-fold increase in sensitivity, (2) improved reproducibility, (3) a four-fold increase in throughput, allowing 1,536 samples to be processed per lab worker per week, and (4) reduced sample preparation costs.Thus, LC-MS-based platelet proteomics offers a compelling alternative to immunoaffinity assays (which depend on antibody availability and quality), as well as to genomic assays (which can only reveal genotypes). In summary, in conjunction with recent advances in LC-MS instrumentation, our platform represents a highly valuable tool for rapid phenotyping of platelets in research with extraordinary potential for future employment in companion or routine diagnostics.
{"title":"Middle-throughput LC-MS-based Platelet Proteomics with Minute Sample Amounts Using Semiautomated Positive Pressure FASP in 384-Well Format.","authors":"Stefan Loroch, Eleftherios Panagiotidis, Kristoffer Klewe, Frauke Swieringa, Johan W M Heemskerk, Jan-Paul Lerch, Andreas Greinacher, Ulrich Walter, Kerstin Jurk, Tobias John, Katalin Barkovits, Thomas Dandekar, Katrin Marcus, Johannes Balkenhol","doi":"10.1055/a-2516-1812","DOIUrl":"10.1055/a-2516-1812","url":null,"abstract":"<p><p>Comprehensive characterization of platelets requires various functional assays and analytical techniques, including omics disciplines, each demanding a separate aliquot of the given sample. Consequently, sample material for each assay is often highly limited, necessitating the downscaling of methods to work with just a few micrograms of platelet protein.Here, we present a novel sample preparation platform for proteomics analysis using only 3 μg of purified platelet protein, corresponding to 2 × 10<sup>6</sup> platelets, which can be obtained from approximately 2 to 8 μL of blood from a healthy individual (1.5 × 10<sup>5</sup>-4.5 × 10<sup>5</sup> platelets/μL) or approximately 100 μL of blood from a patient with severe thrombocytopenia (<2 × 10<sup>4</sup> platelets/µL).Using this platform, we detected a significant fraction of key players in the platelet activation cascade and, most importantly, identified 36 clinically relevant platelet disease markers even with a non-state-of-the art instrument. This makes LC-MS-based proteomics a highly attractive alternative to conventional assays, which often require milliliters of blood. Our platform transitions from our previously established 96-well proteomics workflow (PF96), which has been successfully employed in numerous platelet proteomics studies, into the 384-well format. This transition is accompanied by (1) a more than two-fold increase in sensitivity, (2) improved reproducibility, (3) a four-fold increase in throughput, allowing 1,536 samples to be processed per lab worker per week, and (4) reduced sample preparation costs.Thus, LC-MS-based platelet proteomics offers a compelling alternative to immunoaffinity assays (which depend on antibody availability and quality), as well as to genomic assays (which can only reveal genotypes). In summary, in conjunction with recent advances in LC-MS instrumentation, our platform represents a highly valuable tool for rapid phenotyping of platelets in research with extraordinary potential for future employment in companion or routine diagnostics.</p>","PeriodicalId":23036,"journal":{"name":"Thrombosis and haemostasis","volume":" ","pages":""},"PeriodicalIF":5.0,"publicationDate":"2025-03-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143012019","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":"Inhibitor formation in the era of novel haemophilia treatment - a humanized mouse model to answer our questions?","authors":"Lize F D van Vulpen, Simon C Mastbergen","doi":"10.1055/a-2551-8561","DOIUrl":"https://doi.org/10.1055/a-2551-8561","url":null,"abstract":"<p><p>No Abstract.</p>","PeriodicalId":23036,"journal":{"name":"Thrombosis and haemostasis","volume":" ","pages":""},"PeriodicalIF":5.0,"publicationDate":"2025-03-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143573741","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}
Xin-Yi Yu, Xin-Yu Jia, Ting-Yu Wang, Yan-Hong Zhang, Hao Song, Kan Li, Zhuo-Zheng Chen, Yi Zhu, Liu Yao
Patients with coronavirus disease 2019 (COVID-19) are at high risk of developing a hypercoagulable state and thrombosis. The von Willebrand factor (vWF) produced by endothelial cells (ECs) is a critical thrombosis regulator. We previously found that cytoskeleton-associated protein 4 (CKAP4) is a novel receptor for the spike protein of severe acute respiratory syndrome coronavirus-2 and is involved in COVID-19-associated coagulopathy. However, the underlying mechanism involved remains unclear. This study aimed to explore the signaling pathways involved in spike protein-CKAP4-induced vWF secretion and thrombosis. Treatment of ECs with the spike protein significantly induced vWF secretion, coagulation factor VIII (FVIII)-vWF binding, and platelet adhesion to ECs, which were blocked by the selective intracellular calcium chelator, BAPTA-AM. Furthermore, using several calcium channel-blocking drugs and small-molecule inhibitors, we found that calcium released from the endoplasmic reticulum (ER) is involved in this process. IP3 (inositol 1,4,5-trisphosphate) receptors (IP3Rs) inhibition ameliorated spike protein-induced vWF secretion, FVIII-vWF binding affinity, and platelet adhesion to ECs. Specifically, the knockdown of IP3R1, a crucial type of IP3Rs, reversed spike protein-induced endothelial vWF secretion, and the procoagulant state. Moreover, KT-362, an investigational and clinically relevant antihypertensive drug targeting IP3Rs-mediated calcium release, repressed spike protein-induced endothelial vWF secretion. Conversely, the IP3Rs agonist promoted endothelial vWF secretion, which was not affected by CKAP4 knockdown. In vivo treatment of endothelial-specific human CKAP4 overexpression mice with KT-362 retarded spike protein-induced vWF secretion and thrombosis. Thus, IP3Rs mediated calcium release from the ER and contributed to spike protein-induced vWF secretion and thrombosis, making them potential therapeutic targets for COVID-19-associated coagulopathy.
{"title":"Inhibition of IP3 (Inositol 1,4,5-Trisphosphate) Receptors Retards SARS-CoV-2-Induced Endothelial von Willebrand Factor Secretion and Thrombosis.","authors":"Xin-Yi Yu, Xin-Yu Jia, Ting-Yu Wang, Yan-Hong Zhang, Hao Song, Kan Li, Zhuo-Zheng Chen, Yi Zhu, Liu Yao","doi":"10.1055/a-2471-8767","DOIUrl":"https://doi.org/10.1055/a-2471-8767","url":null,"abstract":"<p><p>Patients with coronavirus disease 2019 (COVID-19) are at high risk of developing a hypercoagulable state and thrombosis. The von Willebrand factor (vWF) produced by endothelial cells (ECs) is a critical thrombosis regulator. We previously found that cytoskeleton-associated protein 4 (CKAP4) is a novel receptor for the spike protein of severe acute respiratory syndrome coronavirus-2 and is involved in COVID-19-associated coagulopathy. However, the underlying mechanism involved remains unclear. This study aimed to explore the signaling pathways involved in spike protein-CKAP4-induced vWF secretion and thrombosis. Treatment of ECs with the spike protein significantly induced vWF secretion, coagulation factor VIII (FVIII)-vWF binding, and platelet adhesion to ECs, which were blocked by the selective intracellular calcium chelator, BAPTA-AM. Furthermore, using several calcium channel-blocking drugs and small-molecule inhibitors, we found that calcium released from the endoplasmic reticulum (ER) is involved in this process. IP3 (inositol 1,4,5-trisphosphate) receptors (IP3Rs) inhibition ameliorated spike protein-induced vWF secretion, FVIII-vWF binding affinity, and platelet adhesion to ECs. Specifically, the knockdown of IP3R1, a crucial type of IP3Rs, reversed spike protein-induced endothelial vWF secretion, and the procoagulant state. Moreover, KT-362, an investigational and clinically relevant antihypertensive drug targeting IP3Rs-mediated calcium release, repressed spike protein-induced endothelial vWF secretion. Conversely, the IP3Rs agonist promoted endothelial vWF secretion, which was not affected by CKAP4 knockdown. In vivo treatment of endothelial-specific human CKAP4 overexpression mice with KT-362 retarded spike protein-induced vWF secretion and thrombosis. Thus, IP3Rs mediated calcium release from the ER and contributed to spike protein-induced vWF secretion and thrombosis, making them potential therapeutic targets for COVID-19-associated coagulopathy.</p>","PeriodicalId":23036,"journal":{"name":"Thrombosis and haemostasis","volume":" ","pages":""},"PeriodicalIF":5.0,"publicationDate":"2025-03-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143574117","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}
Ramón Lecumberri, María Marcos-Jubilar, José Hermida, Pedro Ruiz-Artacho
The outcome of venous thromboembolism in patients with cancer is worse than in patients without cancer, with a higher risk of recurrences, bleeding and death. However, these risks appear to vary depending on the cancer type. While in some tumours the risk of recurrences outweighs the risk of bleeding, in others the risk of major bleeding (MB) during the anticoagulation markedly exceeds the risk of a recurrent event. Balancing these risks could be helpful to tailor the management of cancer-associated thrombosis (CAT) and improve outcomes. In this article, published data from recent randomized clinical trials as well as from some large registries that have reported separated outcomes of CAT depending on cancer type were reviewed. A careful balance of the risk of recurrences and MB events could provide useful insights for clinicians for individualizing treatment strategies in order to improve the outcomes of CAT, as well as for the design of future clinical trials.
{"title":"Differences in the Outcome of Cancer-Associated Thrombosis Depending on Cancer Type.","authors":"Ramón Lecumberri, María Marcos-Jubilar, José Hermida, Pedro Ruiz-Artacho","doi":"10.1055/a-2535-7400","DOIUrl":"10.1055/a-2535-7400","url":null,"abstract":"<p><p>The outcome of venous thromboembolism in patients with cancer is worse than in patients without cancer, with a higher risk of recurrences, bleeding and death. However, these risks appear to vary depending on the cancer type. While in some tumours the risk of recurrences outweighs the risk of bleeding, in others the risk of major bleeding (MB) during the anticoagulation markedly exceeds the risk of a recurrent event. Balancing these risks could be helpful to tailor the management of cancer-associated thrombosis (CAT) and improve outcomes. In this article, published data from recent randomized clinical trials as well as from some large registries that have reported separated outcomes of CAT depending on cancer type were reviewed. A careful balance of the risk of recurrences and MB events could provide useful insights for clinicians for individualizing treatment strategies in order to improve the outcomes of CAT, as well as for the design of future clinical trials.</p>","PeriodicalId":23036,"journal":{"name":"Thrombosis and haemostasis","volume":" ","pages":""},"PeriodicalIF":5.0,"publicationDate":"2025-03-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143391845","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}
T Gregorio, K J Creeper, L Pagliani, R Providencia, A Buzea, C Wallenhorst, J I Weitz, A T Cohen
The duration of anticoagulation treatment for venous thromboembolism (VTE) depends on whether the event was provoked or unprovoked. Major surgery or trauma are well-established major provoking factors associated with a low risk of recurrence, but the magnitude of risk with VTE after minor surgery or trauma is uncertain.To compare the rate of recurrence in patients with VTE provoked by minor surgery or trauma with that in patients with VTE provoked by major surgery or trauma.Nested, case-control study of patients with a first VTE diagnosed within 90 days after major or minor surgery or trauma. Patients with unprovoked VTE or VTE provoked by cancer or nonsurgical risk factors were excluded. Crude and adjusted odds ratios with 95% confidence intervals (CI) were calculated and results were adjusted for potential confounders.A total of 319 patients with recurrent VTE (cases) were matched to 974 patients without recurrence (controls). The incidence of recurrence after VTE provoked by minor surgery (6.5%; 95% CI: 5.6-7.6) was more than double that after VTE provoked by major surgery (3.0%; 95% CI: 2.4-3.6), a difference that remained even after adjustment for known VTE risk factors. There were no differences in recurrence rates between VTE provoked by minor and major trauma.The risk of recurrence is higher in patients with VTE provoked by minor surgery than major surgery. These findings support the concept that the risk of recurrence is higher with minimally provoked VTE than with VTE provoked by major transient risk factors.
{"title":"Relationship between Surgery and Trauma and Risk of Recurrence in Patients with an Associated First Venous Thrombotic Event: A Nested Case-Control Study.","authors":"T Gregorio, K J Creeper, L Pagliani, R Providencia, A Buzea, C Wallenhorst, J I Weitz, A T Cohen","doi":"10.1055/a-2535-7321","DOIUrl":"https://doi.org/10.1055/a-2535-7321","url":null,"abstract":"<p><p>The duration of anticoagulation treatment for venous thromboembolism (VTE) depends on whether the event was provoked or unprovoked. Major surgery or trauma are well-established major provoking factors associated with a low risk of recurrence, but the magnitude of risk with VTE after minor surgery or trauma is uncertain.To compare the rate of recurrence in patients with VTE provoked by minor surgery or trauma with that in patients with VTE provoked by major surgery or trauma.Nested, case-control study of patients with a first VTE diagnosed within 90 days after major or minor surgery or trauma. Patients with unprovoked VTE or VTE provoked by cancer or nonsurgical risk factors were excluded. Crude and adjusted odds ratios with 95% confidence intervals (CI) were calculated and results were adjusted for potential confounders.A total of 319 patients with recurrent VTE (cases) were matched to 974 patients without recurrence (controls). The incidence of recurrence after VTE provoked by minor surgery (6.5%; 95% CI: 5.6-7.6) was more than double that after VTE provoked by major surgery (3.0%; 95% CI: 2.4-3.6), a difference that remained even after adjustment for known VTE risk factors. There were no differences in recurrence rates between VTE provoked by minor and major trauma.The risk of recurrence is higher in patients with VTE provoked by minor surgery than major surgery. These findings support the concept that the risk of recurrence is higher with minimally provoked VTE than with VTE provoked by major transient risk factors.</p>","PeriodicalId":23036,"journal":{"name":"Thrombosis and haemostasis","volume":" ","pages":""},"PeriodicalIF":5.0,"publicationDate":"2025-03-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143568215","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}
Pub Date : 2025-03-01Epub Date: 2024-07-01DOI: 10.1055/a-2358-0853
Alejandra Reyes Ruiz, Aishwarya S Bhale, Krishnan Venkataraman, Jordan D Dimitrov, Sébastien Lacroix-Desmazes
The binding promiscuity of proteins defines their ability to indiscriminately bind multiple unrelated molecules. Binding promiscuity is implicated, at least in part, in the off-target reactivity, nonspecific biodistribution, immunogenicity, and/or short half-life of potentially efficacious protein drugs, thus affecting their clinical use. In this review, we discuss the current evidence for the binding promiscuity of factor VIII (FVIII), a protein used for the treatment of hemophilia A, which displays poor pharmacokinetics, and elevated immunogenicity. We summarize the different canonical and noncanonical interactions that FVIII may establish in the circulation and that could be responsible for its therapeutic liabilities. We also provide information suggesting that the FVIII light chain, and especially its C1 and C2 domains, could play an important role in the binding promiscuity. We believe that the knowledge accumulated over years of FVIII usage could be exploited for the development of strategies to predict protein binding promiscuity and therefore anticipate drug efficacy and toxicity. This would open a mutational space to reduce the binding promiscuity of emerging protein drugs while conserving their therapeutic potency.
{"title":"Binding Promiscuity of Therapeutic Factor VIII.","authors":"Alejandra Reyes Ruiz, Aishwarya S Bhale, Krishnan Venkataraman, Jordan D Dimitrov, Sébastien Lacroix-Desmazes","doi":"10.1055/a-2358-0853","DOIUrl":"10.1055/a-2358-0853","url":null,"abstract":"<p><p>The binding promiscuity of proteins defines their ability to indiscriminately bind multiple unrelated molecules. Binding promiscuity is implicated, at least in part, in the off-target reactivity, nonspecific biodistribution, immunogenicity, and/or short half-life of potentially efficacious protein drugs, thus affecting their clinical use. In this review, we discuss the current evidence for the binding promiscuity of factor VIII (FVIII), a protein used for the treatment of hemophilia A, which displays poor pharmacokinetics, and elevated immunogenicity. We summarize the different canonical and noncanonical interactions that FVIII may establish in the circulation and that could be responsible for its therapeutic liabilities. We also provide information suggesting that the FVIII light chain, and especially its C1 and C2 domains, could play an important role in the binding promiscuity. We believe that the knowledge accumulated over years of FVIII usage could be exploited for the development of strategies to predict protein binding promiscuity and therefore anticipate drug efficacy and toxicity. This would open a mutational space to reduce the binding promiscuity of emerging protein drugs while conserving their therapeutic potency.</p>","PeriodicalId":23036,"journal":{"name":"Thrombosis and haemostasis","volume":" ","pages":"194-206"},"PeriodicalIF":5.0,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141477498","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}
Pub Date : 2025-03-01Epub Date: 2025-01-20DOI: 10.1055/a-2508-5708
Giuseppe Boriani, Davide Antonio Mei, Gregory Y H Lip
{"title":"A European-Multicenter Network for the Implementation of Artificial Intelligence to Manage Complexity and Comorbidities of Atrial Fibrillation Patients: The ARISTOTELES Consortium.","authors":"Giuseppe Boriani, Davide Antonio Mei, Gregory Y H Lip","doi":"10.1055/a-2508-5708","DOIUrl":"10.1055/a-2508-5708","url":null,"abstract":"","PeriodicalId":23036,"journal":{"name":"Thrombosis and haemostasis","volume":" ","pages":"189-193"},"PeriodicalIF":5.0,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143042049","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}
Pub Date : 2025-03-01Epub Date: 2024-11-12DOI: 10.1055/a-2441-8902
Daniela Poli
{"title":"Off-Label Dosing of Direct Oral Anticoagulants: Prescribing Error or Opportunity in Treating Patients with Atrial Fibrillation?","authors":"Daniela Poli","doi":"10.1055/a-2441-8902","DOIUrl":"10.1055/a-2441-8902","url":null,"abstract":"","PeriodicalId":23036,"journal":{"name":"Thrombosis and haemostasis","volume":" ","pages":"286-289"},"PeriodicalIF":5.0,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142627486","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}
Pub Date : 2025-03-01Epub Date: 2024-02-01DOI: 10.1055/a-2259-0662
Alexander T Cohen, Christopher Wallenhorst, Marcella Rivera, Cihan Ay, Bernhard Schaefer, Khaled Abdelgawwad, George Psaroudakis, Gunnar Brobert, Anders Ekbom, Agnes Y Y Lee, Alok A Khorana, Cecilia Becattini, Marc Carrier, Craig I Coleman, Carlos Martinez
Background: In most patients with cancer-associated venous thromboembolism (CT), essentially those not at high risk of bleeding, guidelines recommend treatment with direct oral anticoagulants as an alternative to low-molecular-weight heparins (LMWHs). Population-based studies comparing these therapies are scarce.
Objectives: To compare the risk of venous thromboembolism (VTE) recurrences, significant bleeding, and all-cause mortality in patients with CT receiving rivaroxaban or LMWHs.
Patients/methods: Using UK Clinical Practice Research Datalink data from 2013 to 2020, we generated a cohort of patients with first CT treated initially with either rivaroxaban or LMWH. Patients were observed 12 months for VTE recurrences, significant bleeds (major bleeds or clinically relevant nonmajor bleeding requiring hospitalization), and all-cause mortality. Overlap weighted sub-distribution hazard ratios (SHRs) compared rivaroxaban with LMWH in an intention-to-treat analysis.
Results: The cohort consisted of 2,259 patients with first CT, 314 receiving rivaroxaban, and 1,945 LMWH, mean age 72.4 and 66.9 years, respectively. In the 12-month observational period, 184 person-years following rivaroxaban and 1,057 following LMWH, 10 and 66 incident recurrent VTE events, 20 and 102 significant bleeds, and 10 and 133 deaths were observed in rivaroxaban and LMWH users, respectively. The weighted SHR at 12 months for VTE recurrences in rivaroxaban compared with LMWH were 0.80 (0.37-1.73); for significant bleeds 1.01 (0.57-1.81); and for all-cause mortality 0.49 (0.23-1.06).
Conclusion: Patients with CT, not at high risk of bleeding, treated with either rivaroxaban or LMWH have comparable effectiveness and safety outcomes. This supports the recommendation that rivaroxaban is a reasonable alternative to LMWH for the treatment of CT.
{"title":"Comparison of Clinical Outcomes in Patients with Active Cancer Receiving Rivaroxaban or Low-Molecular-Weight Heparin: The OSCAR-UK Study.","authors":"Alexander T Cohen, Christopher Wallenhorst, Marcella Rivera, Cihan Ay, Bernhard Schaefer, Khaled Abdelgawwad, George Psaroudakis, Gunnar Brobert, Anders Ekbom, Agnes Y Y Lee, Alok A Khorana, Cecilia Becattini, Marc Carrier, Craig I Coleman, Carlos Martinez","doi":"10.1055/a-2259-0662","DOIUrl":"10.1055/a-2259-0662","url":null,"abstract":"<p><strong>Background: </strong> In most patients with cancer-associated venous thromboembolism (CT), essentially those not at high risk of bleeding, guidelines recommend treatment with direct oral anticoagulants as an alternative to low-molecular-weight heparins (LMWHs). Population-based studies comparing these therapies are scarce.</p><p><strong>Objectives: </strong> To compare the risk of venous thromboembolism (VTE) recurrences, significant bleeding, and all-cause mortality in patients with CT receiving rivaroxaban or LMWHs.</p><p><strong>Patients/methods: </strong> Using UK Clinical Practice Research Datalink data from 2013 to 2020, we generated a cohort of patients with first CT treated initially with either rivaroxaban or LMWH. Patients were observed 12 months for VTE recurrences, significant bleeds (major bleeds or clinically relevant nonmajor bleeding requiring hospitalization), and all-cause mortality. Overlap weighted sub-distribution hazard ratios (SHRs) compared rivaroxaban with LMWH in an intention-to-treat analysis.</p><p><strong>Results: </strong> The cohort consisted of 2,259 patients with first CT, 314 receiving rivaroxaban, and 1,945 LMWH, mean age 72.4 and 66.9 years, respectively. In the 12-month observational period, 184 person-years following rivaroxaban and 1,057 following LMWH, 10 and 66 incident recurrent VTE events, 20 and 102 significant bleeds, and 10 and 133 deaths were observed in rivaroxaban and LMWH users, respectively. The weighted SHR at 12 months for VTE recurrences in rivaroxaban compared with LMWH were 0.80 (0.37-1.73); for significant bleeds 1.01 (0.57-1.81); and for all-cause mortality 0.49 (0.23-1.06).</p><p><strong>Conclusion: </strong> Patients with CT, not at high risk of bleeding, treated with either rivaroxaban or LMWH have comparable effectiveness and safety outcomes. This supports the recommendation that rivaroxaban is a reasonable alternative to LMWH for the treatment of CT.</p>","PeriodicalId":23036,"journal":{"name":"Thrombosis and haemostasis","volume":" ","pages":"265-277"},"PeriodicalIF":5.0,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11858610/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139672755","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}