Pub Date : 2024-07-11DOI: 10.1016/j.thromres.2024.109090
Plasma proteins involved in coagulation and fibrinolysis are essential to hemostasis. Consequently, their circulating levels and functionality are critical in bleeding and thrombosis development. Well-established laboratory tests to assess these are available; however, said tests do not allow high multiplicity, require large volumes of plasma and are often costly. A novel technology to quantify plasma proteins is quantitative protein mass spectrometry (QPMS). Aided by stable isotope-labeled internal standards a large number of proteins can be quantified in one single analytical run requiring <30 μL of plasma. This provides an opportunity to improve insight in the etiology and prognosis of bleeding and thrombotic disorders, in which the balance between different proteins plays a crucial role. This manuscript aims to give an overview of the QPMS potential applications in thrombosis and hemostasis research (quantifying the 38 proteins assigned to coagulation and fibrinolysis by the KEGG database), but also to explore the potential and hurdles if designed for clinical practice. Advantages and limitations of QPMS are described and strategies for improved analysis are proposed, using as an example the test requirements for antithrombin. Application of this technology in the future could represent a step towards individualized patient care.
{"title":"Quantitative protein mass spectrometry for multiplex measurement of coagulation and fibrinolytic proteins towards clinical application: What, why and how?","authors":"","doi":"10.1016/j.thromres.2024.109090","DOIUrl":"10.1016/j.thromres.2024.109090","url":null,"abstract":"<div><p>Plasma proteins involved in coagulation and fibrinolysis are essential to hemostasis. Consequently, their circulating levels and functionality are critical in bleeding and thrombosis development. Well-established laboratory tests to assess these are available; however, said tests do not allow high multiplicity, require large volumes of plasma and are often costly. A novel technology to quantify plasma proteins is quantitative protein mass spectrometry (QPMS). Aided by stable isotope-labeled internal standards a large number of proteins can be quantified in one single analytical run requiring <30 μL of plasma. This provides an opportunity to improve insight in the etiology and prognosis of bleeding and thrombotic disorders, in which the balance between different proteins plays a crucial role. This manuscript aims to give an overview of the QPMS potential applications in thrombosis and hemostasis research (quantifying the 38 proteins assigned to coagulation and fibrinolysis by the KEGG database), but also to explore the potential and hurdles if designed for clinical practice. Advantages and limitations of QPMS are described and strategies for improved analysis are proposed, using as an example the test requirements for antithrombin. Application of this technology in the future could represent a step towards individualized patient care.</p></div>","PeriodicalId":23064,"journal":{"name":"Thrombosis research","volume":null,"pages":null},"PeriodicalIF":3.7,"publicationDate":"2024-07-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S0049384824002226/pdfft?md5=83c8dc46d44601e59a31bdbb331406dd&pid=1-s2.0-S0049384824002226-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141696821","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}
Pub Date : 2024-07-11DOI: 10.1016/j.thromres.2024.109096
{"title":"Thromboembolic complications following recreational use of nitrous oxide: A French Addictovigilance alert","authors":"","doi":"10.1016/j.thromres.2024.109096","DOIUrl":"10.1016/j.thromres.2024.109096","url":null,"abstract":"","PeriodicalId":23064,"journal":{"name":"Thrombosis research","volume":null,"pages":null},"PeriodicalIF":3.7,"publicationDate":"2024-07-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141636787","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
A variety of thromboprophylaxis regimens have been administered in patients following the Fontan procedure. However, consensus guidelines regarding the optimal thromboprophylaxis strategy have not yet been developed.
Method
A network meta-analysis was conducted to evaluate the comparative effectiveness among available thromboprophylaxis regimens and major bleeding events associated with these regimens.
Results
A total of 28 comparative studies with 4430 Fontan patients were included. The incidence of thromboembolic events (TE) was significantly lower in individuals who underwent thromboprophylaxis compared to those who did not. Compared to a no-treatment strategy, nonvitamin K oral anticoagulants (NOACs) showed the largest treatment effect for preventing TE (OR = 0.08, 95 % CI 0.03 to 0.21), followed by warfarin (OR = 0.16, 95 % CI 0.10 to 0.27), and aspirin (OR = 0.23, 95 % CI 0.14 to 0.38). Indeed, NOACs were significantly more effective than aspirin in preventing TE (OR = 0.35, 95 % CI 0.14 to 0.84). Aspirin was associated with the lowest occurrence of major bleeding events, followed by NOACs, no medication, and warfarin. NOACs were shown to possess a highly favorable overall profile.
Conclusion
Prescribing thromboprophylaxis drugs, either antiplatelets or anticoagulants, may be more effective in preventing TE after the Fontan operation than not doing so. Among the included regimens, NOACs demonstrated significantly greater efficacy than aspirin; however, they did not show statistically significant superiority over warfarin. Aspirin exhibited lower rates of major bleeding compared to both NOACs and warfarin. Overall, NOACs tended to offer the most advantageous balance of efficacy and safety. However, the findings should be interpreted considering the certainty and limitations of the evidence, including potential residual confounding in observational studies.
导言:目前已对接受丰坦手术的患者实施了多种血栓预防方案。方法 进行了一项网络荟萃分析,以评估现有血栓预防方案的有效性比较以及与这些方案相关的大出血事件。结果 共纳入28项比较研究,4430名Fontan患者。与未采取血栓预防措施的患者相比,采取血栓预防措施的患者血栓栓塞事件(TE)发生率明显较低。与不采取治疗策略相比,非维生素K口服抗凝药(NOACs)对预防血栓栓塞事件的治疗效果最好(OR = 0.08,95 % CI 0.03 至 0.21),其次是华法林(OR = 0.16,95 % CI 0.10 至 0.27)和阿司匹林(OR = 0.23,95 % CI 0.14 至 0.38)。事实上,NOAC 在预防 TE 方面的效果明显优于阿司匹林(OR = 0.35,95 % CI 0.14 至 0.84)。阿司匹林的大出血事件发生率最低,其次是 NOACs、不用药和华法林。结论在丰坦手术后使用抗血小板或抗凝药物预防血栓形成可能比不使用更有效。在纳入的治疗方案中,NOACs的疗效明显优于阿司匹林;但在统计学上,NOACs与华法林相比并无明显优势。与 NOACs 和华法林相比,阿司匹林的大出血率较低。总体而言,NOAC 在疗效和安全性之间的平衡最具优势。不过,在解释研究结果时应考虑到证据的确定性和局限性,包括观察性研究中可能存在的残余混杂因素。
{"title":"Comparative effectiveness among thromboprophylaxis strategies after the Fontan operation: A systematic review and network meta-analysis","authors":"Saviga Sethasathien , Phichayut Phinyo , Rekwan Sittiwangkul , Suchaya Silvilairat","doi":"10.1016/j.thromres.2024.109093","DOIUrl":"https://doi.org/10.1016/j.thromres.2024.109093","url":null,"abstract":"<div><h3>Introduction</h3><p>A variety of thromboprophylaxis regimens have been administered in patients following the Fontan procedure. However, consensus guidelines regarding the optimal thromboprophylaxis strategy have not yet been developed.</p></div><div><h3>Method</h3><p>A network meta-analysis was conducted to evaluate the comparative effectiveness among available thromboprophylaxis regimens and major bleeding events associated with these regimens.</p></div><div><h3>Results</h3><p>A total of 28 comparative studies with 4430 Fontan patients were included. The incidence of thromboembolic events (TE) was significantly lower in individuals who underwent thromboprophylaxis compared to those who did not. Compared to a no-treatment strategy, nonvitamin K oral anticoagulants (NOACs) showed the largest treatment effect for preventing TE (OR = 0.08, 95 % CI 0.03 to 0.21), followed by warfarin (OR = 0.16, 95 % CI 0.10 to 0.27), and aspirin (OR = 0.23, 95 % CI 0.14 to 0.38). Indeed, NOACs were significantly more effective than aspirin in preventing TE (OR = 0.35, 95 % CI 0.14 to 0.84). Aspirin was associated with the lowest occurrence of major bleeding events, followed by NOACs, no medication, and warfarin. NOACs were shown to possess a highly favorable overall profile.</p></div><div><h3>Conclusion</h3><p>Prescribing thromboprophylaxis drugs, either antiplatelets or anticoagulants, may be more effective in preventing TE after the Fontan operation than not doing so. Among the included regimens, NOACs demonstrated significantly greater efficacy than aspirin; however, they did not show statistically significant superiority over warfarin. Aspirin exhibited lower rates of major bleeding compared to both NOACs and warfarin. Overall, NOACs tended to offer the most advantageous balance of efficacy and safety. However, the findings should be interpreted considering the certainty and limitations of the evidence, including potential residual confounding in observational studies.</p></div>","PeriodicalId":23064,"journal":{"name":"Thrombosis research","volume":null,"pages":null},"PeriodicalIF":3.7,"publicationDate":"2024-07-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141607710","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-07-07DOI: 10.1016/j.thromres.2024.109092
Background
Leukocyte-platelet aggregates comprise a pathogenic link between hemostasis and immunity, but the prerequisites and mechanisms of their formation remain not understood.
Aims
To quantify the formation, composition, and morphology of leukocyte-platelet aggregates in vitro under the influence of various cellular activators.
Methods
Phorbol-12-myristate-13-acetate (PMA), lipopolysaccharide (LPS), thrombin receptor-activating peptide (TRAP-6), and adenosine diphosphate (ADP) were used as cellular activators. Flow cytometry was utilized to identify and quantify aggregates in whole human blood and platelet-rich plasma. Cell types and cellular aggregates were identified using fluorescently labeled antibodies against the appropriate cellular markers, and cell activation was assessed by the expression of appropriate surface markers. For confocal fluorescent microscopy, cell membranes and nuclei were labeled. Neutrophil-platelet aggregates were studied using scanning electron microscopy.
Results
In the presence of PMA, ADP or TRAP-6, about 17–38 % of neutrophils and 61–77 % of monocytes formed aggregates with platelets in whole blood, whereas LPS did not induce platelet aggregation with either neutrophils or monocytes due the inability to activate platelets. Similar results were obtained when isolated neutrophils were added to platelet-rich plasma. All the cell types involved in the heterotypic aggregation expressed molecular markers of activation. Fluorescent and electron microscopy of the aggregates showed that the predominant platelet/leukocyte ratios were 1:1 and 2:1.
Conclusions
Formation of leukocyte-platelet aggregates depends on the nature of the cellular activator and the spectrum of its cell-activating ability. An indispensable condition for formation of leukocyte-platelet aggregates is activation of all cell types including platelets, which is the restrictive step.
{"title":"The differential formation and composition of leukocyte-platelet aggregates induced by various cellular stimulants","authors":"","doi":"10.1016/j.thromres.2024.109092","DOIUrl":"10.1016/j.thromres.2024.109092","url":null,"abstract":"<div><h3>Background</h3><p>Leukocyte-platelet aggregates comprise a pathogenic link between hemostasis and immunity, but the prerequisites and mechanisms of their formation remain not understood.</p></div><div><h3>Aims</h3><p>To quantify the formation, composition, and morphology of leukocyte-platelet aggregates in vitro under the influence of various cellular activators.</p></div><div><h3>Methods</h3><p>Phorbol-12-myristate-13-acetate (PMA), lipopolysaccharide (LPS), thrombin receptor-activating peptide (TRAP-6), and adenosine diphosphate (ADP) were used as cellular activators. Flow cytometry was utilized to identify and quantify aggregates in whole human blood and platelet-rich plasma. Cell types and cellular aggregates were identified using fluorescently labeled antibodies against the appropriate cellular markers, and cell activation was assessed by the expression of appropriate surface markers. For confocal fluorescent microscopy, cell membranes and nuclei were labeled. Neutrophil-platelet aggregates were studied using scanning electron microscopy.</p></div><div><h3>Results</h3><p>In the presence of PMA, ADP or TRAP-6, about 17–38 % of neutrophils and 61–77 % of monocytes formed aggregates with platelets in whole blood, whereas LPS did not induce platelet aggregation with either neutrophils or monocytes due the inability to activate platelets. Similar results were obtained when isolated neutrophils were added to platelet-rich plasma. All the cell types involved in the heterotypic aggregation expressed molecular markers of activation. Fluorescent and electron microscopy of the aggregates showed that the predominant platelet/leukocyte ratios were 1:1 and 2:1.</p></div><div><h3>Conclusions</h3><p>Formation of leukocyte-platelet aggregates depends on the nature of the cellular activator and the spectrum of its cell-activating ability. An indispensable condition for formation of leukocyte-platelet aggregates is activation of all cell types including platelets, which is the restrictive step.</p></div>","PeriodicalId":23064,"journal":{"name":"Thrombosis research","volume":null,"pages":null},"PeriodicalIF":3.7,"publicationDate":"2024-07-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141638925","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-07-06DOI: 10.1016/j.thromres.2024.109094
Marwan Hamiko MD , Lena Gerdes , Miriam Silaschi MD , Holger Seidel MD , Philipp Westhofen PhD , Johannes Kruppenbacher MD , Hans-Joerg Hertfelder MD, PhD , Johannes Oldenburg MD , Farhad Bakhtiary MD , Markus Velten MD , Mehmet Oezkur MD , Georg Daniel Duerr MD
Background
Severe aortic stenosis (sAS) is associated with acquired von Willebrand syndrome (AVWS) by loss of high-molecular-weight multimers (HMWM) of von Willebrand factor (VWF), potentially resulting in perioperative bleeding. Analysis of VWF multimers remains challenging. Recently, the new, rapid Hydragel 5 assay has been developed, using electrophoretic protein separation for dividing VWF-multimers into low (LMWM), intermediate (IMWM), and HMWM, the hemostatically active part of VWF. Here, we evaluated its impact on predicting blood loss in presence of AVWS after surgical aortic valve replacement (SAVR).
Methods
We prospectively examined 52 patients (age: 68 ± 7 years; 54 % male) admitted to SAVR. They were divided in two groups (A: normal VWF, n = 28; B: abnormal VWF, n = 24, defined as VWF-activity/antigen (VWF:Ac/Ag)-ratio < 0.7 and/or HMWM loss). Blood samples and echocardiographic data were collected before, seven days and three months after SAVR. Blood loss and transfusions were recorded.
Results
Baseline characteristics and clinical data were similar in both groups. HMWM loss was present in 38.5 % of all patients. HMWM, the VWF:Ac/Ag- and HMWM/(IMWM+LMWM)-ratios were significantly decreased preoperatively in group B but normalized after SAVR. Bleeding, re-thoracotomy and transfusion rates were comparable. HMWM loss was inversely correlated with the peak aortic gradient (Pmax) and positively with the aortic valve area (AVA), while HMWM/(IMWM+LMWM)-ratio negatively correlated with the mean aortic gradient (Pmean).
Conclusion
HMWM and HMWM/(IMWM+LMWM)-ratio inversely correlate with severity of AS and normalize after SAVR. The Hydragel-5 assay's might be valuable for routine diagnostics to assess bleeding risk and postoperative normalization of AS and VWF abnormalities in SAVR patients.
{"title":"Investigation of von Willebrand factor multimer abnormalities before and after aortic valve replacement using the Hydragel-5 assay","authors":"Marwan Hamiko MD , Lena Gerdes , Miriam Silaschi MD , Holger Seidel MD , Philipp Westhofen PhD , Johannes Kruppenbacher MD , Hans-Joerg Hertfelder MD, PhD , Johannes Oldenburg MD , Farhad Bakhtiary MD , Markus Velten MD , Mehmet Oezkur MD , Georg Daniel Duerr MD","doi":"10.1016/j.thromres.2024.109094","DOIUrl":"10.1016/j.thromres.2024.109094","url":null,"abstract":"<div><h3>Background</h3><p>Severe aortic stenosis (sAS) is associated with acquired von Willebrand syndrome (AVWS) by loss of high-molecular-weight multimers (HMWM) of von Willebrand factor (VWF), potentially resulting in perioperative bleeding. Analysis of VWF multimers remains challenging. Recently, the new, rapid Hydragel 5 assay has been developed, using electrophoretic protein separation for dividing VWF-multimers into low (LMWM), intermediate (IMWM), and HMWM, the hemostatically active part of VWF. Here, we evaluated its impact on predicting blood loss in presence of AVWS after surgical aortic valve replacement (SAVR).</p></div><div><h3>Methods</h3><p>We prospectively examined 52 patients (age: 68 ± 7 years; 54 % male) admitted to SAVR. They were divided in two groups (A: normal VWF, <em>n</em> = 28; B: abnormal VWF, <em>n</em> = 24, defined as VWF-activity/antigen (VWF:Ac/Ag)-ratio < 0.7 and/or HMWM loss). Blood samples and echocardiographic data were collected before, seven days and three months after SAVR. Blood loss and transfusions were recorded.</p></div><div><h3>Results</h3><p>Baseline characteristics and clinical data were similar in both groups. HMWM loss was present in 38.5 % of all patients. HMWM, the VWF:Ac/Ag- and HMWM/(IMWM+LMWM)-ratios were significantly decreased preoperatively in group B but normalized after SAVR. Bleeding, re-thoracotomy and transfusion rates were comparable. HMWM loss was inversely correlated with the peak aortic gradient (Pmax) and positively with the aortic valve area (AVA), while HMWM/(IMWM+LMWM)-ratio negatively correlated with the mean aortic gradient (Pmean).</p></div><div><h3>Conclusion</h3><p>HMWM and HMWM/(IMWM+LMWM)-ratio inversely correlate with severity of AS and normalize after SAVR. The Hydragel-5 assay's might be valuable for routine diagnostics to assess bleeding risk and postoperative normalization of AS and VWF abnormalities in SAVR patients.</p></div>","PeriodicalId":23064,"journal":{"name":"Thrombosis research","volume":null,"pages":null},"PeriodicalIF":3.7,"publicationDate":"2024-07-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S0049384824002263/pdfft?md5=e34c4ba5e21da1022259ed46d63e94c5&pid=1-s2.0-S0049384824002263-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141591463","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}
Pub Date : 2024-07-06DOI: 10.1016/j.thromres.2024.109095
Introduction
The 2021 Surviving Sepsis Campaign guidelines recommend low-molecular-weight heparin for the prevention of venous thromboembolism in sepsis. However, observational studies suggest that anticoagulants as a whole may benefit severely ill sepsis patients with coagulopathy, but the optimal targets of unfractionated heparin remain unclear. This study investigated which sepsis patients could most benefit from unfractionated heparin.
Materials and methods
In this retrospective observational study, we identified adult sepsis patients requiring urgent hospitalization from 2006 to 2019 using a large-scale Japanese medical database. Patients were divided into two groups: those receiving unfractionated heparin within 72 h of admission and those who did not. We compared in-hospital mortality, major bleeding complications, and thromboembolic events between these groups using a multivariate logistic regression model adjusted for patient and treatment variables. Additionally, we assessed the association between heparin administration and in-hospital mortality across various subgroups.
Results
Among 30,342 sepsis patients, 2520 received early heparin administration, and 27,822 did not. Multivariate logistic regression revealed a significant association between heparin and reduced in-hospital mortality (adjusted OR: 0.735, 95 % CI: 0.596–0.903) but no significant association with major bleeding and thromboembolic risk (adjusted OR: 1.137, 1.243; 95 % CI: 0.926–1.391, 0.853–1.788, respectively). Subgroup analyses suggested significant survival benefits associated with heparin only in the sepsis patients with moderate coagulopathy and sepsis-induced coagulopathy scores of 3 or 4 (adjusted OR: 0.452, 0.625; 95 % CI: 0.265–0.751, 0.410–0.940, respectively).
Conclusions
Early heparin administration upon admission is associated with lower in-hospital mortality, especially in moderate sepsis-induced coagulopathy, and no significant increase in complications.
{"title":"Efficacy of unfractionated heparin in patients with moderate sepsis-induced coagulopathy: An observational study","authors":"","doi":"10.1016/j.thromres.2024.109095","DOIUrl":"10.1016/j.thromres.2024.109095","url":null,"abstract":"<div><h3>Introduction</h3><p>The 2021 Surviving Sepsis Campaign guidelines recommend low-molecular-weight heparin for the prevention of venous thromboembolism in sepsis. However, observational studies suggest that anticoagulants as a whole may benefit severely ill sepsis patients with coagulopathy, but the optimal targets of unfractionated heparin remain unclear. This study investigated which sepsis patients could most benefit from unfractionated heparin.</p></div><div><h3>Materials and methods</h3><p>In this retrospective observational study, we identified adult sepsis patients requiring urgent hospitalization from 2006 to 2019 using a large-scale Japanese medical database. Patients were divided into two groups: those receiving unfractionated heparin within 72 h of admission and those who did not. We compared in-hospital mortality, major bleeding complications, and thromboembolic events between these groups using a multivariate logistic regression model adjusted for patient and treatment variables. Additionally, we assessed the association between heparin administration and in-hospital mortality across various subgroups.</p></div><div><h3>Results</h3><p>Among 30,342 sepsis patients, 2520 received early heparin administration, and 27,822 did not. Multivariate logistic regression revealed a significant association between heparin and reduced in-hospital mortality (adjusted OR: 0.735, 95 % CI: 0.596–0.903) but no significant association with major bleeding and thromboembolic risk (adjusted OR: 1.137, 1.243; 95 % CI: 0.926–1.391, 0.853–1.788, respectively). Subgroup analyses suggested significant survival benefits associated with heparin only in the sepsis patients with moderate coagulopathy and sepsis-induced coagulopathy scores of 3 or 4 (adjusted OR: 0.452, 0.625; 95 % CI: 0.265–0.751, 0.410–0.940, respectively).</p></div><div><h3>Conclusions</h3><p>Early heparin administration upon admission is associated with lower in-hospital mortality, especially in moderate sepsis-induced coagulopathy, and no significant increase in complications.</p></div>","PeriodicalId":23064,"journal":{"name":"Thrombosis research","volume":null,"pages":null},"PeriodicalIF":3.7,"publicationDate":"2024-07-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S0049384824002275/pdfft?md5=5535be9578ecc2cff3e57fd2de9825a8&pid=1-s2.0-S0049384824002275-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141636786","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}
Pub Date : 2024-07-06DOI: 10.1016/j.thromres.2024.109087
Introduction
Hormone therapy (HT) for breast cancer is associated with an increased risk of venous thromboembolism (VTE). This study examines the effects of continuing versus discontinuing HT on VTE recurrence, major bleeding, and mortality, after an acute VTE event.
Methods
Using data in the RIETE-registry from March 2001 through September 2021, we calculated incidence rates and rate-ratios (RR) for VTE events in patients on- and off HT. Cox regression models assessed the impact of HT continuation.
Results
Among 479 women with breast cancer on HT who developed VTE (pulmonary embolism 279, isolated deep vein thrombosis 200), 350 (73 %) continued HT. These women were slightly older (70 ± 13 vs. 67 ± 16 years) than those discontinuing HT, with no significant differences in other baseline characteristics. Over a median follow-up of 294 days, 25 (5.2 %) developed VTE recurrences, 18 (3.7 %) had major bleeding, and 73 (15.2 %) died. Rates of VTE recurrence did not differ significantly between groups (RR: 1.28, 95 % CI 0.44–3.75), except in the first three months post-VTE, where a higher rate was observed in those continuing HT (6.02/100 patients-year vs. no events). On multivariable analysis, HT continuation showed no association with VTE recurrences after adjusting for other thromboembolic risk factors (adjusted hazard ratio [aHR] 1.49, 95 % CI 0.5–4.45).
Conclusion
Continuing HT after a VTE event in women with breast cancer does not generally affect the long-term risk of VTE recurrences but is associated with a higher risk in the first three months. These findings highlight the need for careful monitoring during this period.
{"title":"Venous thromboembolism in women with hormone-dependent breast cancer. To continue or discontinue hormonal treatment? Insights from the RIETE registry","authors":"","doi":"10.1016/j.thromres.2024.109087","DOIUrl":"10.1016/j.thromres.2024.109087","url":null,"abstract":"<div><h3>Introduction</h3><p>Hormone therapy (HT) for breast cancer is associated with an increased risk of venous thromboembolism (VTE). This study examines the effects of continuing <em>versus</em> discontinuing HT on VTE recurrence, major bleeding, and mortality, after an acute VTE event.</p></div><div><h3>Methods</h3><p>Using data in the RIETE-registry from March 2001 through September 2021, we calculated incidence rates and rate-ratios (RR) for VTE events in patients on- and off HT. Cox regression models assessed the impact of HT continuation.</p></div><div><h3>Results</h3><p>Among 479 women with breast cancer on HT who developed VTE (pulmonary embolism 279, isolated deep vein thrombosis 200), 350 (73 %) continued HT. These women were slightly older (70 ± 13 <em>vs.</em> 67 ± 16 years) than those discontinuing HT, with no significant differences in other baseline characteristics. Over a median follow-up of 294 days, 25 (5.2 %) developed VTE recurrences, 18 (3.7 %) had major bleeding, and 73 (15.2 %) died. Rates of VTE recurrence did not differ significantly between groups (RR: 1.28, 95 % CI 0.44–3.75), except in the first three months post-VTE, where a higher rate was observed in those continuing HT (6.02/100 patients-year <em>vs.</em> no events). On multivariable analysis, HT continuation showed no association with VTE recurrences after adjusting for other thromboembolic risk factors (adjusted hazard ratio [aHR] 1.49, 95 % CI 0.5–4.45).</p></div><div><h3>Conclusion</h3><p>Continuing HT after a VTE event in women with breast cancer does not generally affect the long-term risk of VTE recurrences but is associated with a higher risk in the first three months. These findings highlight the need for careful monitoring during this period.</p></div>","PeriodicalId":23064,"journal":{"name":"Thrombosis research","volume":null,"pages":null},"PeriodicalIF":3.7,"publicationDate":"2024-07-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141622890","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-07-05DOI: 10.1016/j.thromres.2024.109091
Hung-Yen Ke , Jye-Hann Chen , Shih-Yao Kao , Cheng-Ming Tsao , Chia-Wen Kuo , Chin-Chen Wu , Chih-Chin Shih
Introduction
Heatstroke is a critical heat-related condition characterized by coagulopathy and multiple organ dysfunction. One of the most severe complications of heatstroke is disseminated intravascular coagulation. This condition manifests as excessive clot formation and bleeding that are primarily due to platelet depletion and dysfunction. Fibrinogen plays a crucial role in hemostasis because it links integrin αIIbβ3 on adjacent platelets, thereby promoting the platelet activation and aggregation necessary for clot formation. However, reduced fibrinogen levels may impair the formation of the initial platelet plug and increase the risk of bleeding. The current study explored the effect of fibrinogen on platelet dysfunction in a heatstroke model.
Materials and methods
Male Wistar rats were subjected to heat stress, and subsequent changes in hemodynamic, biochemical, and coagulation parameters were analyzed. Platelet viability, aggregation, adhesion, spreading and fibrin clot retraction were assessed.
Results
The rats with heatstroke exhibited a variety of clinical symptoms, including hypotension, tachycardia, multiple organ dysfunction, and coagulopathy. Platelet viability in the heatstroke group was comparable to that in the healthy control group. However, the heatstroke group exhibited significant reductions in plasma fibrinogen levels and platelet aggregation, adhesion, spreading, and fibrin clot retraction. Notably, fibrinogen supplementation markedly augmented the aggregation responses of platelets in the heatstroke group. The impairment of platelet adhesion, spreading, and fibrin clot retraction in the rats with heatstroke was partially ameliorated by fibrinogen supplementation.
Conclusions
An early use of fibrinogen replacement may serve as a therapeutic intervention to alleviate platelet hyporeactivity and prevent the complications in patients with heatstroke.
{"title":"Heat stress–induced platelet dysfunction is associated with loss of fibrinogen and is improved by fibrinogen supplementation","authors":"Hung-Yen Ke , Jye-Hann Chen , Shih-Yao Kao , Cheng-Ming Tsao , Chia-Wen Kuo , Chin-Chen Wu , Chih-Chin Shih","doi":"10.1016/j.thromres.2024.109091","DOIUrl":"10.1016/j.thromres.2024.109091","url":null,"abstract":"<div><h3>Introduction</h3><p>Heatstroke is a critical heat-related condition characterized by coagulopathy and multiple organ dysfunction. One of the most severe complications of heatstroke is disseminated intravascular coagulation. This condition manifests as excessive clot formation and bleeding that are primarily due to platelet depletion and dysfunction. Fibrinogen plays a crucial role in hemostasis because it links integrin αIIbβ3 on adjacent platelets, thereby promoting the platelet activation and aggregation necessary for clot formation. However, reduced fibrinogen levels may impair the formation of the initial platelet plug and increase the risk of bleeding. The current study explored the effect of fibrinogen on platelet dysfunction in a heatstroke model.</p></div><div><h3>Materials and methods</h3><p>Male Wistar rats were subjected to heat stress, and subsequent changes in hemodynamic, biochemical, and coagulation parameters were analyzed. Platelet viability, aggregation, adhesion, spreading and fibrin clot retraction were assessed.</p></div><div><h3>Results</h3><p>The rats with heatstroke exhibited a variety of clinical symptoms, including hypotension, tachycardia, multiple organ dysfunction, and coagulopathy. Platelet viability in the heatstroke group was comparable to that in the healthy control group. However, the heatstroke group exhibited significant reductions in plasma fibrinogen levels and platelet aggregation, adhesion, spreading, and fibrin clot retraction. Notably, fibrinogen supplementation markedly augmented the aggregation responses of platelets in the heatstroke group. The impairment of platelet adhesion, spreading, and fibrin clot retraction in the rats with heatstroke was partially ameliorated by fibrinogen supplementation.</p></div><div><h3>Conclusions</h3><p>An early use of fibrinogen replacement may serve as a therapeutic intervention to alleviate platelet hyporeactivity and prevent the complications in patients with heatstroke.</p></div>","PeriodicalId":23064,"journal":{"name":"Thrombosis research","volume":null,"pages":null},"PeriodicalIF":3.7,"publicationDate":"2024-07-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141580906","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-07-05DOI: 10.1016/j.thromres.2024.109089
Giuseppe Lippi , Camilla Mattiuzzi
{"title":"Analysis of real-world data pulmonary embolism as the underlying cause of death during the COVID-19 pandemic","authors":"Giuseppe Lippi , Camilla Mattiuzzi","doi":"10.1016/j.thromres.2024.109089","DOIUrl":"10.1016/j.thromres.2024.109089","url":null,"abstract":"","PeriodicalId":23064,"journal":{"name":"Thrombosis research","volume":null,"pages":null},"PeriodicalIF":3.7,"publicationDate":"2024-07-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141555500","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-07-03DOI: 10.1016/j.thromres.2024.109086
Konrad Stępień , Jakub Siudut , Jarosław Zalewski , Tomasz Nowakowski , Anetta Undas
Introduction
Postthrombotic syndrome (PTS), a common complication of deep vein thrombosis (DVT), is largely inflammatory by nature with contribution of prothrombotic mechanisms. The role of factor (F)XI in PTS has not been explored yet. We investigated whether elevated FXI is associated with PTS occurrence.
Materials and methods
We enrolled 180 consecutive patients (aged 43 ± 13 years) with first-ever DVT. After 3 months FXI levels were measured, along with inflammatory markers, thrombin generation, plasma clot permeability (Ks), clot lysis time (CLT), and fibrinolysis proteins. We assessed PTS using the Villalta score and recorded symptomatic venous thromboembolism (VTE) at a 1-year and venous ulcers at a median 53 months follow-up.
Results
Baseline median FXI was 102 % [IQR 92–113 %] and showed positive association with Villalta score (R = 0.474, P < 0.001). Patients with PTS (n = 48, 26.7 %) had 16.1 % higher FXI (P < 0.001) and FXI ≥120 % occurred more often in PTS patients (odds ratio [OR] 5.55, 95 % confidence interval [CI] 2.28–13.47). There were associations of baseline FXI with Ks and CLT along with thrombin activatable fibrinolysis inhibitor (TAFI) activity, C-reactive protein, and interleukin-6, but not with fibrinogen, or thrombin generation. After age adjustment higher FXI was independently associated with PTS occurrence (OR per 1 % 1.06, 95 % CI 1.02–1.09) and VTE recurrence (OR 1.03, 95 % CI 1.01–1.06). At long-term follow-up, patients with venous ulcers had 13.6 % higher baseline FXI (P = 0.002).
Conclusions
Elevated FXI in association with inflammation and prothrombotic fibrin clot properties may contribute to the development of PTS following DVT.
{"title":"Elevated plasma factor XI is associated with postthrombotic syndrome","authors":"Konrad Stępień , Jakub Siudut , Jarosław Zalewski , Tomasz Nowakowski , Anetta Undas","doi":"10.1016/j.thromres.2024.109086","DOIUrl":"10.1016/j.thromres.2024.109086","url":null,"abstract":"<div><h3>Introduction</h3><p>Postthrombotic syndrome (PTS), a common complication of deep vein thrombosis (DVT), is largely inflammatory by nature with contribution of prothrombotic mechanisms. The role of factor (F)XI in PTS has not been explored yet. We investigated whether elevated FXI is associated with PTS occurrence.</p></div><div><h3>Materials and methods</h3><p>We enrolled 180 consecutive patients (aged 43 ± 13 years) with first-ever DVT. After 3 months FXI levels were measured, along with inflammatory markers, thrombin generation, plasma clot permeability (Ks), clot lysis time (CLT), and fibrinolysis proteins. We assessed PTS using the Villalta score and recorded symptomatic venous thromboembolism (VTE) at a 1-year and venous ulcers at a median 53 months follow-up.</p></div><div><h3>Results</h3><p>Baseline median FXI was 102 % [IQR 92–113 %] and showed positive association with Villalta score (<em>R</em> = 0.474, <em>P</em> < 0.001). Patients with PTS (<em>n</em> = 48, 26.7 %) had 16.1 % higher FXI (P < 0.001) and FXI ≥120 % occurred more often in PTS patients (odds ratio [OR] 5.55, 95 % confidence interval [CI] 2.28–13.47). There were associations of baseline FXI with Ks and CLT along with thrombin activatable fibrinolysis inhibitor (TAFI) activity, C-reactive protein, and interleukin-6, but not with fibrinogen, or thrombin generation. After age adjustment higher FXI was independently associated with PTS occurrence (OR per 1 % 1.06, 95 % CI 1.02–1.09) and VTE recurrence (OR 1.03, 95 % CI 1.01–1.06). At long-term follow-up, patients with venous ulcers had 13.6 % higher baseline FXI (<em>P</em> = 0.002).</p></div><div><h3>Conclusions</h3><p>Elevated FXI in association with inflammation and prothrombotic fibrin clot properties may contribute to the development of PTS following DVT.</p></div>","PeriodicalId":23064,"journal":{"name":"Thrombosis research","volume":null,"pages":null},"PeriodicalIF":3.7,"publicationDate":"2024-07-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141538681","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}