Pub Date : 2024-09-18DOI: 10.1016/j.jtha.2024.09.001
Ton Lisman , Suzanne C. Cannegieter
{"title":"First impressions","authors":"Ton Lisman , Suzanne C. Cannegieter","doi":"10.1016/j.jtha.2024.09.001","DOIUrl":"10.1016/j.jtha.2024.09.001","url":null,"abstract":"","PeriodicalId":17326,"journal":{"name":"Journal of Thrombosis and Haemostasis","volume":"22 10","pages":"Page 2677"},"PeriodicalIF":5.5,"publicationDate":"2024-09-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142271307","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 : 2024-09-18DOI: 10.1016/S1538-7836(24)00531-2
{"title":"Annoucements","authors":"","doi":"10.1016/S1538-7836(24)00531-2","DOIUrl":"10.1016/S1538-7836(24)00531-2","url":null,"abstract":"","PeriodicalId":17326,"journal":{"name":"Journal of Thrombosis and Haemostasis","volume":"22 10","pages":"Page 2942"},"PeriodicalIF":5.5,"publicationDate":"2024-09-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S1538783624005312/pdfft?md5=7a2d8c10bc1b94f82cd924a5af5bfc43&pid=1-s2.0-S1538783624005312-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142272488","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}
Pub Date : 2024-09-17DOI: 10.1016/j.jtha.2024.08.020
Elizabeth A Andraska, Frederik Denorme, Christof Kaltenmeier, Aishwarrya Arivudainabi, Emily P Mihalko, Mitchell Dyer, Gowtham K Annarapu, Mohammadreza Zarisfi, Patricia Loughran, Mehves Ozel, Kelly Williamson, Roberto Mota-Alvidrez, Kimberly Thomas, Sruti Shiva, Susan Shea, Richard A Steinman, Robert A Campbell, Matthew R Rosengart, Matthew D Neal
The publisher regrets that this article has been temporarily removed. A replacement will appear as soon as possible in which the reason for the removal of the article will be specified, or the article will be reinstated. The full Elsevier Policy on Article Withdrawal can be found at: https://www.elsevier.com/about/policies/article-withdrawal.
{"title":"TEMPORARY REMOVAL: Alterations in visible light exposure modulate platelet function and regulate thrombus formation.","authors":"Elizabeth A Andraska, Frederik Denorme, Christof Kaltenmeier, Aishwarrya Arivudainabi, Emily P Mihalko, Mitchell Dyer, Gowtham K Annarapu, Mohammadreza Zarisfi, Patricia Loughran, Mehves Ozel, Kelly Williamson, Roberto Mota-Alvidrez, Kimberly Thomas, Sruti Shiva, Susan Shea, Richard A Steinman, Robert A Campbell, Matthew R Rosengart, Matthew D Neal","doi":"10.1016/j.jtha.2024.08.020","DOIUrl":"10.1016/j.jtha.2024.08.020","url":null,"abstract":"<p><p>The publisher regrets that this article has been temporarily removed. A replacement will appear as soon as possible in which the reason for the removal of the article will be specified, or the article will be reinstated. The full Elsevier Policy on Article Withdrawal can be found at: https://www.elsevier.com/about/policies/article-withdrawal.</p>","PeriodicalId":17326,"journal":{"name":"Journal of Thrombosis and Haemostasis","volume":" ","pages":""},"PeriodicalIF":5.5,"publicationDate":"2024-09-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142289958","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 : 2024-09-17DOI: 10.1016/j.jtha.2024.08.022
Ruben D Hupperetz, Aaron F J Iding, Jorinde van Laanen, Rutger Brans, Pascale Notten, Lidwine W Tick, Louis-Jean Vleming, Asiong Jie, Nils Planken, Cees H A Wittens, Hugo Ten Cate, Arina J Ten Cate-Hoek
Objectives: This Ultrasound-Accelerated Catheter-Directed Thrombolysis Versus Anticoagulation for the Prevention of Post-Thrombotic Syndrome (CAVA) trial subanalysis investigated the effect of ultrasound-accelerated catheter-directed thrombolysis (UACDT) on patency, reflux, and their relevance in PTS development.
Methods: This multicenter, randomized, single-blind trial enrolled patients (aged 18-85 years) with a first iliofemoral deep vein thrombosis and symptom duration ≤14 days. Patency and reflux were assessed by duplex ultrasound at 12 months (T12) and long-term (LT) follow-up (median, 39.5 months; IQR, 24.0-63.0 months). PTS was diagnosed using the Villalta score.
Results: UACDT significantly improved patency in all vein segments at T12 (60.3% UACDT vs 25.9% standard treatment [ST]; P = .002) and LT (45.2% UACDT vs 11.9% ST; P < .001). Popliteal patency, however, was similar between groups (87.9% UACDT vs 83.3% ST; P = .487). Reflux was similar between groups at T12 and LT; only popliteal reflux was significantly reduced in the UACDT group at LT (22.6% UACDT vs 44.8% ST; P = .010). Absent iliac patency at T12 was associated with increased PTS risk in the ST group only (odds ratio [OR], 10.84; 95% CI, 1.93-60.78; P = .007). In the UACDT group, popliteal reflux at T12 was associated with moderate-to-severe PTS at T12 (OR, 4.88; 95% CI, 1.10-21.57; P = .041) and LT (OR, 5.83; 95% CI, 1.44-23.63; P = .009). Combined popliteal reflux and absent iliac patency significantly amplified PTS risk (OR, 10.79; 95% CI, 2.41-48.42; P < .001).
Conclusion: UACDT improved patency and reduced popliteal reflux. Iliac patency and popliteal reflux are independently associated with moderate-to-severe PTS and contribute synergistically to its development. However, a proportion of moderate-to-severe PTS cases lacks an evident underlying cause.
背景:辅助性导管引导溶栓(CDT)在预防血栓后综合征(PTS)方面的疗效不一,尽管其通畅性已经恢复:这项CAVA试验的子分析研究了超声加速(UA)CDT对通畅性和回流的影响及其与PTS发展的相关性:这项多中心、随机、单盲试验招募了首次髂股深静脉血栓形成(DVT)且症状持续时间不超过14天的患者(18-85岁)。12个月(T12)和长期(LT)随访(中位数为39.5(24.0-63.0)个月)时,通过双工超声(DUS)评估了通畅和反流情况。采用 Villalta 评分诊断 PTS:结果:UACDT明显改善了T12(60.3% UACDT vs. 25.9% 标准治疗(ST),P=0.002)和LT(45.2% UACDT vs. 11.9% ST,P结论:UACDT改善了通畅性,减少了腘窝回流。髂骨通畅和腘窝反流与中重度 PTS 独立相关,并对其发展起到协同作用。然而,一部分中度重度 PTS 病例缺乏明显的潜在病因。
{"title":"Patency and reflux in relation to postthrombotic syndrome: a subanalysis of the Ultrasound-Accelerated Catheter-Directed Thrombolysis Versus Anticoagulation for the Prevention of Post-Thrombotic Syndrome trial.","authors":"Ruben D Hupperetz, Aaron F J Iding, Jorinde van Laanen, Rutger Brans, Pascale Notten, Lidwine W Tick, Louis-Jean Vleming, Asiong Jie, Nils Planken, Cees H A Wittens, Hugo Ten Cate, Arina J Ten Cate-Hoek","doi":"10.1016/j.jtha.2024.08.022","DOIUrl":"10.1016/j.jtha.2024.08.022","url":null,"abstract":"<p><strong>Background: </strong>Adjunctive catheter-directed thrombolysis shows variable efficacy in preventing postthrombotic syndrome (PTS), despite restored patency.</p><p><strong>Objectives: </strong>This Ultrasound-Accelerated Catheter-Directed Thrombolysis Versus Anticoagulation for the Prevention of Post-Thrombotic Syndrome (CAVA) trial subanalysis investigated the effect of ultrasound-accelerated catheter-directed thrombolysis (UACDT) on patency, reflux, and their relevance in PTS development.</p><p><strong>Methods: </strong>This multicenter, randomized, single-blind trial enrolled patients (aged 18-85 years) with a first iliofemoral deep vein thrombosis and symptom duration ≤14 days. Patency and reflux were assessed by duplex ultrasound at 12 months (T12) and long-term (LT) follow-up (median, 39.5 months; IQR, 24.0-63.0 months). PTS was diagnosed using the Villalta score.</p><p><strong>Results: </strong>UACDT significantly improved patency in all vein segments at T12 (60.3% UACDT vs 25.9% standard treatment [ST]; P = .002) and LT (45.2% UACDT vs 11.9% ST; P < .001). Popliteal patency, however, was similar between groups (87.9% UACDT vs 83.3% ST; P = .487). Reflux was similar between groups at T12 and LT; only popliteal reflux was significantly reduced in the UACDT group at LT (22.6% UACDT vs 44.8% ST; P = .010). Absent iliac patency at T12 was associated with increased PTS risk in the ST group only (odds ratio [OR], 10.84; 95% CI, 1.93-60.78; P = .007). In the UACDT group, popliteal reflux at T12 was associated with moderate-to-severe PTS at T12 (OR, 4.88; 95% CI, 1.10-21.57; P = .041) and LT (OR, 5.83; 95% CI, 1.44-23.63; P = .009). Combined popliteal reflux and absent iliac patency significantly amplified PTS risk (OR, 10.79; 95% CI, 2.41-48.42; P < .001).</p><p><strong>Conclusion: </strong>UACDT improved patency and reduced popliteal reflux. Iliac patency and popliteal reflux are independently associated with moderate-to-severe PTS and contribute synergistically to its development. However, a proportion of moderate-to-severe PTS cases lacks an evident underlying cause.</p>","PeriodicalId":17326,"journal":{"name":"Journal of Thrombosis and Haemostasis","volume":" ","pages":""},"PeriodicalIF":5.5,"publicationDate":"2024-09-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142289964","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 : 2024-09-17DOI: 10.1016/j.jtha.2024.08.024
Divya Sharma, Christopher D Barrett, Hunter B Moore, Joe H Jackson, Tanner M Sandberg, Flobater I Gawargi, Trace B Moody, Xiaoyue Cheng, Corey J Georgesen, Erin X Wei
{"title":"Resistance to tPA-induced fibrinolysis and activation of coagulation is present in autoimmune bullous diseases of the skin.","authors":"Divya Sharma, Christopher D Barrett, Hunter B Moore, Joe H Jackson, Tanner M Sandberg, Flobater I Gawargi, Trace B Moody, Xiaoyue Cheng, Corey J Georgesen, Erin X Wei","doi":"10.1016/j.jtha.2024.08.024","DOIUrl":"10.1016/j.jtha.2024.08.024","url":null,"abstract":"","PeriodicalId":17326,"journal":{"name":"Journal of Thrombosis and Haemostasis","volume":" ","pages":""},"PeriodicalIF":5.5,"publicationDate":"2024-09-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142289965","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 : 2024-09-17DOI: 10.1016/j.jtha.2024.08.021
Julie Hahn, Gerard Temprano-Sagrera, Natalie R Hasbani, Symen Ligthart, Abbas Dehghan, Alisa S Wolberg, Nicholas L Smith, Maria Sabater-Lleal, Alanna C Morrison, Paul S de Vries
Background: Fibrinogen and C-reactive protein (CRP) play an important role in inflammatory pathways and share multiple genetic loci reported in previously published genome-wide association studies (GWAS), highlighting their common genetic background. Leveraging the shared biology may identify further loci pleiotropically associated with both fibrinogen and CRP.
Objectives: To identify novel genetic variants that are pleiotropic and associated with both fibrinogen and CRP, by integrating both phenotypes in a bivariate GWAS by using a multitrait GWAS.
Methods: We performed a bivariate GWAS to identify further pleiotropic genetic loci, using summary statistics of previously published GWAS on fibrinogen (n = 120 246) from the Cohorts for Heart and Aging Research in Genomic Epidemiology Consortium, consisting of European ancestry samples and CRP (n = 363 228) from UK Biobank, including 5 different population groups. The main analysis was performed using metaUSAT and N-GWAMA. We conducted replication for novel CRP associations to test the robustness of the findings using an independent GWAS for CRP (n = 148 164). We also performed colocalization analysis to compare the associations in identified loci for the 2 traits and Genotype-Tissue Expression data.
Results: We identified 87 pleiotropic loci that overlapped between metaUSAT and N-GWAMA, including 23 previously known for either fibrinogen or CRP, 58 novel loci for fibrinogen, and 6 novel loci for both fibrinogen and CRP. Overall, there were 30 pleiotropic and novel loci for both traits, and 7 of these showed evidence of colocalization, located in or near ZZZ3, NR1I2, RP11-72L22.1, MICU1, ARL14EP, SOCS2, and PGM5. Among these 30 loci, 13 replicated for CRP in an independent CRP GWAS.
Conclusion: Bivariate GWAS identified additional associated loci for fibrinogen and CRP. This analysis suggests fibrinogen and CRP share a common genetic architecture with many pleiotropic loci.
{"title":"Bivariate genome-wide association study of circulating fibrinogen and C-reactive protein levels.","authors":"Julie Hahn, Gerard Temprano-Sagrera, Natalie R Hasbani, Symen Ligthart, Abbas Dehghan, Alisa S Wolberg, Nicholas L Smith, Maria Sabater-Lleal, Alanna C Morrison, Paul S de Vries","doi":"10.1016/j.jtha.2024.08.021","DOIUrl":"10.1016/j.jtha.2024.08.021","url":null,"abstract":"<p><strong>Background: </strong>Fibrinogen and C-reactive protein (CRP) play an important role in inflammatory pathways and share multiple genetic loci reported in previously published genome-wide association studies (GWAS), highlighting their common genetic background. Leveraging the shared biology may identify further loci pleiotropically associated with both fibrinogen and CRP.</p><p><strong>Objectives: </strong>To identify novel genetic variants that are pleiotropic and associated with both fibrinogen and CRP, by integrating both phenotypes in a bivariate GWAS by using a multitrait GWAS.</p><p><strong>Methods: </strong>We performed a bivariate GWAS to identify further pleiotropic genetic loci, using summary statistics of previously published GWAS on fibrinogen (n = 120 246) from the Cohorts for Heart and Aging Research in Genomic Epidemiology Consortium, consisting of European ancestry samples and CRP (n = 363 228) from UK Biobank, including 5 different population groups. The main analysis was performed using metaUSAT and N-GWAMA. We conducted replication for novel CRP associations to test the robustness of the findings using an independent GWAS for CRP (n = 148 164). We also performed colocalization analysis to compare the associations in identified loci for the 2 traits and Genotype-Tissue Expression data.</p><p><strong>Results: </strong>We identified 87 pleiotropic loci that overlapped between metaUSAT and N-GWAMA, including 23 previously known for either fibrinogen or CRP, 58 novel loci for fibrinogen, and 6 novel loci for both fibrinogen and CRP. Overall, there were 30 pleiotropic and novel loci for both traits, and 7 of these showed evidence of colocalization, located in or near ZZZ3, NR1I2, RP11-72L22.1, MICU1, ARL14EP, SOCS2, and PGM5. Among these 30 loci, 13 replicated for CRP in an independent CRP GWAS.</p><p><strong>Conclusion: </strong>Bivariate GWAS identified additional associated loci for fibrinogen and CRP. This analysis suggests fibrinogen and CRP share a common genetic architecture with many pleiotropic loci.</p>","PeriodicalId":17326,"journal":{"name":"Journal of Thrombosis and Haemostasis","volume":" ","pages":""},"PeriodicalIF":5.5,"publicationDate":"2024-09-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142289960","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}
Background: The ONCO DVT study (Edoxaban for 12 Months Versus 3 Months in Patients With Cancer With Isolated Distal Deep Vein Thrombosis) revealed superiority of 12-month relative to 3-month edoxaban treatment for the thrombotic risk in cancer-associated isolated distal deep vein thrombosis. However, it is unknown whether the superiority could be common in different modified Ottawa score subgroups.
Objectives: To identify more preferable candidates for extended anticoagulation in patients with cancer-associated isolated distal deep vein thrombosis using the modified Ottawa score.
Methods: In this post-hoc subgroup analysis of the ONCO DVT study, we stratified 601 patients into the low (≤-1, N = 126), intermediate (0, N = 323), and high (≥1, N = 152) modified Ottawa score subgroups and compared clinical outcomes between the 12-month and 3-month edoxaban treatment groups.
Results: The cumulative incidence of symptomatic recurrent venous thromboembolism or venous thromboembolism-related death was not different between the 12-month and 3-month edoxaban treatment groups in the low score subgroup (0.0% vs 2.2%), whereas it was lower in the 12-month than in the 3-month edoxaban treatment group in the intermediate (0.8% vs 7.6%) and high (3.1% vs 15.6%) score subgroups. There were no significant differences in the cumulative incidences of the major bleeding between the 12-month and 3-month edoxaban treatment groups in the low (10.1% vs 7.6%), intermediate (8.8% vs 5.0%), and high (13.9% vs 12.6%) score subgroups.
Conclusion: A 12-month compared with 3-month edoxaban treatment showed a lower risk of thrombotic events in patients with cancer-associated isolated distal deep vein thrombosis in the intermediate and high modified Ottawa score subgroups but not in the low score subgroup, suggesting a limited benefit of extended anticoagulation therapy beyond 3 months in patients with low modified Ottawa score.
研究背景ONCO DVT研究显示,在癌症相关孤立远端深静脉血栓(DVT)的血栓风险方面,12个月的依多沙班治疗优于3个月的依多沙班治疗。然而,这种优越性在不同的改良渥太华评分亚组中是否具有共性尚不得而知:在这项 ONCO DVT 研究的事后亚组分析中,我们将 601 例患者分为低(≤-1,N=126)、中(0,N=323)和高(≥1,N=152)改良渥太华评分亚组,并比较了 12 个月和 3 个月依多沙班治疗组的临床结果:在低分亚组中,12个月和3个月依多沙班治疗组的无症状复发性静脉血栓栓塞症(VTE)或VTE相关死亡的累积发生率没有差异(0.0% vs. 2.2%),而在中分(0.8% vs. 7.6%)和高分(3.1% vs. 15.6%)亚组中,12个月依多沙班治疗组的发生率低于3个月依多沙班治疗组。在低分(10.1% vs. 7.6%)、中分(8.8% vs. 5.0%)和高分(13.9% vs. 12.6%)亚组中,埃多沙班治疗12个月组和3个月组的大出血累计发生率无明显差异:为期12个月的依多沙班治疗与为期3个月的依多沙班治疗相比,在中度和高度修改后渥太华评分亚组中,癌症相关孤立性远端深静脉血栓患者发生血栓事件的风险较低,但在低评分亚组中风险不高,这表明在低修改后渥太华评分患者中,延长抗凝治疗3个月以上的获益有限。
{"title":"Utility of the modified Ottawa score for identification of more preferable candidates of extended anticoagulation therapy in cancer-associated isolated distal deep vein thrombosis: insight from the ONCO DVT Study.","authors":"Wei Xiong, Yugo Yamashita, Takeshi Morimoto, Nao Muraoka, Michihisa Umetsu, Yuji Nishimoto, Takuma Takada, Yoshito Ogihara, Tatsuya Nishikawa, Nobutaka Ikeda, Kazunori Otsui, Daisuke Sueta, Yukari Tsubata, Masaaki Shoji, Ayumi Shikama, Yutaka Hosoi, Yasuhiro Tanabe, Ryuki Chatani, Kengo Tsukahara, Naohiko Nakanishi, Kitae Kim, Satoshi Ikeda, Koh Ono, Takeshi Kimura","doi":"10.1016/j.jtha.2024.09.003","DOIUrl":"10.1016/j.jtha.2024.09.003","url":null,"abstract":"<p><strong>Background: </strong>The ONCO DVT study (Edoxaban for 12 Months Versus 3 Months in Patients With Cancer With Isolated Distal Deep Vein Thrombosis) revealed superiority of 12-month relative to 3-month edoxaban treatment for the thrombotic risk in cancer-associated isolated distal deep vein thrombosis. However, it is unknown whether the superiority could be common in different modified Ottawa score subgroups.</p><p><strong>Objectives: </strong>To identify more preferable candidates for extended anticoagulation in patients with cancer-associated isolated distal deep vein thrombosis using the modified Ottawa score.</p><p><strong>Methods: </strong>In this post-hoc subgroup analysis of the ONCO DVT study, we stratified 601 patients into the low (≤-1, N = 126), intermediate (0, N = 323), and high (≥1, N = 152) modified Ottawa score subgroups and compared clinical outcomes between the 12-month and 3-month edoxaban treatment groups.</p><p><strong>Results: </strong>The cumulative incidence of symptomatic recurrent venous thromboembolism or venous thromboembolism-related death was not different between the 12-month and 3-month edoxaban treatment groups in the low score subgroup (0.0% vs 2.2%), whereas it was lower in the 12-month than in the 3-month edoxaban treatment group in the intermediate (0.8% vs 7.6%) and high (3.1% vs 15.6%) score subgroups. There were no significant differences in the cumulative incidences of the major bleeding between the 12-month and 3-month edoxaban treatment groups in the low (10.1% vs 7.6%), intermediate (8.8% vs 5.0%), and high (13.9% vs 12.6%) score subgroups.</p><p><strong>Conclusion: </strong>A 12-month compared with 3-month edoxaban treatment showed a lower risk of thrombotic events in patients with cancer-associated isolated distal deep vein thrombosis in the intermediate and high modified Ottawa score subgroups but not in the low score subgroup, suggesting a limited benefit of extended anticoagulation therapy beyond 3 months in patients with low modified Ottawa score.</p>","PeriodicalId":17326,"journal":{"name":"Journal of Thrombosis and Haemostasis","volume":" ","pages":""},"PeriodicalIF":5.5,"publicationDate":"2024-09-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142289966","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 : 2024-09-13DOI: 10.1016/j.jtha.2024.08.019
Hendy Kristyanto, Leen Slaets, Esmée Braams, Ilse Scheys, Roy Heesbeen, Vicky Cárdenas, Georgi Shukarev, Gert Scheper, Jerald Sadoff, Kerstin Lühn, Hanneke Schuitemaker, Frank Struyf, Jenny Hendriks
Background: Vaccine-induced immune thrombotic thrombocytopenia (VITT) is a rare adverse event identified following vaccination with some adenovirus-vectored COVID-19 vaccines, including Ad26.COV2.S. VITT is characterized by the presence of antibodies against platelet factor 4 (PF4).
Objectives: To evaluate whether PF4 antibodies were generally induced following vaccination with adenovirus type 26 (Ad26)-vectored vaccines.
Methods: The study included 913 and 991 healthy participants without thromboembolic (TE) events in Ad26.COV2.S and non-COVID-19 Ad26-vectored vaccine clinical studies, respectively, and 1 participant with VITT following Ad26.COV2.S vaccination. PF4 antibody levels were measured in prevaccination and postvaccination sera. PF4 antibody positivity rates were assessed in a case-control setting in participants who developed TE events during participation in Ad26-vectored vaccine clinical studies.
Results: In the 1 VITT patient, PF4 antibodies were negative before vaccination. Seroconversion for platelet-activating PF4 antibodies was observed upon Ad26.COV2.S vaccination. In participants without TE events, the PF4 antibody levels and positivity rates were similar before and after Ad26 vaccination. Ad26 vaccination did not increase PF4 antibody levels in participants who were PF4 antibody-positive at baseline (n = 47). Lastly, 1 out of 28 TE cases and 2 out of 156 non-TE controls seroconverted after Ad26.COV2.S vaccination. None of the 15 TE cases and 3 of the 77 non-TE controls seroconverted following non-COVID-19 Ad26 vaccination.
Conclusion: Ad26.COV2.S and the other Ad26-vectored vaccines studied did not generally induce PF4 antibodies or increase preexisting PF4 antibody levels. Moreover, unlike VITT, TE events that occurred at any time following Ad26 vaccination were not associated with PF4 antibodies.
{"title":"Assessment of antibodies against platelet factor 4 following vaccination with adenovirus type 26-vectored vaccines.","authors":"Hendy Kristyanto, Leen Slaets, Esmée Braams, Ilse Scheys, Roy Heesbeen, Vicky Cárdenas, Georgi Shukarev, Gert Scheper, Jerald Sadoff, Kerstin Lühn, Hanneke Schuitemaker, Frank Struyf, Jenny Hendriks","doi":"10.1016/j.jtha.2024.08.019","DOIUrl":"10.1016/j.jtha.2024.08.019","url":null,"abstract":"<p><strong>Background: </strong>Vaccine-induced immune thrombotic thrombocytopenia (VITT) is a rare adverse event identified following vaccination with some adenovirus-vectored COVID-19 vaccines, including Ad26.COV2.S. VITT is characterized by the presence of antibodies against platelet factor 4 (PF4).</p><p><strong>Objectives: </strong>To evaluate whether PF4 antibodies were generally induced following vaccination with adenovirus type 26 (Ad26)-vectored vaccines.</p><p><strong>Methods: </strong>The study included 913 and 991 healthy participants without thromboembolic (TE) events in Ad26.COV2.S and non-COVID-19 Ad26-vectored vaccine clinical studies, respectively, and 1 participant with VITT following Ad26.COV2.S vaccination. PF4 antibody levels were measured in prevaccination and postvaccination sera. PF4 antibody positivity rates were assessed in a case-control setting in participants who developed TE events during participation in Ad26-vectored vaccine clinical studies.</p><p><strong>Results: </strong>In the 1 VITT patient, PF4 antibodies were negative before vaccination. Seroconversion for platelet-activating PF4 antibodies was observed upon Ad26.COV2.S vaccination. In participants without TE events, the PF4 antibody levels and positivity rates were similar before and after Ad26 vaccination. Ad26 vaccination did not increase PF4 antibody levels in participants who were PF4 antibody-positive at baseline (n = 47). Lastly, 1 out of 28 TE cases and 2 out of 156 non-TE controls seroconverted after Ad26.COV2.S vaccination. None of the 15 TE cases and 3 of the 77 non-TE controls seroconverted following non-COVID-19 Ad26 vaccination.</p><p><strong>Conclusion: </strong>Ad26.COV2.S and the other Ad26-vectored vaccines studied did not generally induce PF4 antibodies or increase preexisting PF4 antibody levels. Moreover, unlike VITT, TE events that occurred at any time following Ad26 vaccination were not associated with PF4 antibodies.</p>","PeriodicalId":17326,"journal":{"name":"Journal of Thrombosis and Haemostasis","volume":" ","pages":""},"PeriodicalIF":5.5,"publicationDate":"2024-09-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142289959","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}
Myeloproliferative neoplasms (MPNs) are characterized by a high rate of thrombotic complications that contribute to morbidity and mortality. MPN-related thrombogenesis is assumed to be multifactorial, involving both procoagulant and proinflammatory processes. Whether impaired fibrinolysis also participates in the prothrombotic phenotype of MPN has been poorly investigated.
Objectives
We determined whether MPN, particularly JAK2V617F-positive MPN, is associated with fibrinolytic changes.
Methods
Tissue-type plasminogen activator (tPA)–mediated fibrinolysis was evaluated both in whole blood and plasma from mice with a hematopoietic-restricted Jak2V617F expression compared with wild-type (WT) mice (Jak2WT) using (1) halo clot lysis, (2) front lysis, and (3) plasmin generation assays. tPA clot lysis assay was performed in the plasma from 65 MPN patients (JAK2V617F mutation, n = 50; CALR mutations, n = 9) compared with 28 healthy controls.
Results
In whole blood from Jak2V617F mice, we observed a decreased fibrinolysis characterized by a significantly lower halo clot lysis rate compared with Jak2WT (95 ± 22 vs 147 ± 39 AU/min; P < .05). Similar results were observed in plasma (halo clot lysis rate, 130 ± 27 vs 186 ± 29 AU/min; front lysis rate, 2.8 ± 1.6 vs 6.1 ± 1.2 μm.min−1; P < .05). Plasmin generation was significantly decreased both in plasma clots and standardized fibrin clots from Jak2V617F mice compared with Jak2WT mice. Among MPN patients, impaired tPA-related fibrinolysis with prolonged clot lysis time was observed in JAK2V617F and CALR patients. Plasminogen activator inhibitor-1 and α2-antiplasmin were significantly increased in plasma from JAK2V617F patients compared with controls.
Conclusion
Our results suggest that impaired tPA-mediated fibrinolysis represents an important prothrombotic mechanism in MPN patients that requires confirmation in larger studies.
背景骨髓增殖性肿瘤(MPN)的特点是血栓并发症发生率高,导致死亡率增加。与 MPN 相关的血栓形成被认为是多因素的,涉及促凝血和促炎症过程。纤溶功能受损是否也参与了 MPN 促血栓形成表型的形成,这一问题尚未得到深入研究。患者与野生型小鼠(Jak2WT)相比,我们使用(1)光环凝块裂解法、(2)前端裂解法和(3)血浆蛋白酶生成测定法,对造血受限的 Jak2V617F 表达小鼠的全血(WB)和血浆中组织纤溶酶原激活剂(tPA)介导的纤溶进行了评估。结果在Jak2V617F小鼠的WB中,我们观察到纤维蛋白溶解减少,其特征是与Jak2WT相比,晕凝块溶解率显著降低(95±22 vs 147±39 UA/min,p<0.05)。在血浆中也观察到类似的结果(晕凝块溶解率:130±27 vs 186±29 UA/min):130±27 vs 186±29 UA/min;正面裂解率:2.8±1.6 vs 6.1±1.2 μm.min-1,p<0.05)。与 Jak2WT 小鼠相比,Jak2V617F 小鼠血浆凝块和标准化纤维蛋白凝块中产生的凝血酶明显减少。在骨髓增生性疾病患者中,JAK2V617F 和 CALR 患者的 tPA 相关纤溶功能受损,血块溶解时间延长。与对照组相比,JAK2V617F 患者血浆中的纤溶酶原激活物抑制剂-1 和α-2-抗蛋白酶显著增加。
{"title":"Impaired fibrinolysis in JAK2V617F-related myeloproliferative neoplasms","authors":"Marie-Charlotte Bourrienne , Stéphane Loyau , Dorothée Faille , Juliette Gay , Séléna Akhenak , Carine Farkh , Véronique Ollivier , Mialitiana Solonomenjanahary , Sébastien Dupont , Christine Choqueux , Jean-Luc Villeval , Isabelle Plo , Valérie Edmond , Benoît Ho-Tin-Noé , Nadine Ajzenberg , Mikaël Mazighi","doi":"10.1016/j.jtha.2024.07.031","DOIUrl":"10.1016/j.jtha.2024.07.031","url":null,"abstract":"<div><h3>Background</h3><div>Myeloproliferative neoplasms (MPNs) are characterized by a high rate of thrombotic complications that contribute to morbidity and mortality. MPN-related thrombogenesis is assumed to be multifactorial, involving both procoagulant and proinflammatory processes. Whether impaired fibrinolysis also participates in the prothrombotic phenotype of MPN has been poorly investigated.</div></div><div><h3>Objectives</h3><div>We determined whether MPN, particularly <em>JAK2</em>V617F-positive MPN, is associated with fibrinolytic changes.</div></div><div><h3>Methods</h3><div>Tissue-type plasminogen activator (tPA)–mediated fibrinolysis was evaluated both in whole blood and plasma from mice with a hematopoietic-restricted Jak2<sup>V617F</sup> expression compared with wild-type (WT) mice (Jak2<sup>WT</sup>) using (1) halo clot lysis, (2) front lysis, and (3) plasmin generation assays. tPA clot lysis assay was performed in the plasma from 65 MPN patients (<em>JAK2</em>V617F mutation, <em>n</em> = 50; <em>CALR</em> mutations, <em>n</em> = 9) compared with 28 healthy controls.</div></div><div><h3>Results</h3><div>In whole blood from Jak2<sup>V617F</sup> mice, we observed a decreased fibrinolysis characterized by a significantly lower halo clot lysis rate compared with Jak2<sup>WT</sup> (95 ± 22 vs 147 ± 39 AU/min; <em>P</em> < .05). Similar results were observed in plasma (halo clot lysis rate, 130 ± 27 vs 186 ± 29 AU/min; front lysis rate, 2.8 ± 1.6 vs 6.1 ± 1.2 μm.min<sup>−1</sup>; <em>P</em> < .05). Plasmin generation was significantly decreased both in plasma clots and standardized fibrin clots from Jak2<sup>V617F</sup> mice compared with Jak2<sup>WT</sup> mice. Among MPN patients, impaired tPA-related fibrinolysis with prolonged clot lysis time was observed in <em>JAK2</em>V617F and <em>CALR</em> patients. Plasminogen activator inhibitor-1 and α2-antiplasmin were significantly increased in plasma from <em>JAK2</em>V617F patients compared with controls.</div></div><div><h3>Conclusion</h3><div>Our results suggest that impaired tPA-mediated fibrinolysis represents an important prothrombotic mechanism in MPN patients that requires confirmation in larger studies.</div></div>","PeriodicalId":17326,"journal":{"name":"Journal of Thrombosis and Haemostasis","volume":"22 11","pages":"Pages 3199-3208"},"PeriodicalIF":5.5,"publicationDate":"2024-09-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142182687","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 : 2024-09-12DOI: 10.1016/j.jtha.2024.08.014
Edward Louis George Pryzdial, John Ruggles Perrier, Mahamud-Ur Rashid, Henry Euan West, Michael Ross Sutherland
Many virus types affect the blood clotting system with correlations to pathology that range widely from thrombosis to hemorrhage linking to inflammation. Here we overview the intricate crosstalk induced by infection between proteins on the virus encoded by either the host or virus genomes, coagulation proteins, platelets, leukocytes, and endothelial cells. For blood-borne viruses with an outer covering acquired from the host cell, the envelope, a key player may be the cell-derived trigger of coagulation on the virus surface, tissue factor (TF). TF is a multifunctional transmembrane cofactor that accelerates factor (F)VIIa-dependent activation of FX to FXa, leading to clot formation. However, the nascent TF/FVIIa/FXa complex also facilitates G protein-coupled modulation of cells via protease-activated receptor 2. As a viral envelope constituent, TF can bypass the physiological modes of regulation, thereby initiating the activation of neighboring platelets, leukocytes, and endothelial cells. A thromboinflammatory environment is predicted due to feedback amplification in response to cellular release of cytokines, procoagulant proteins, neutrophil extracellular traps, and stimulus-induced accessibility of adhesive receptors, resulting in cellular aggregates. The pathobiological effects of thromboinflammation ultimately contribute to innate and adaptive immunity for viral clearance. In contrast, the preceding stages of viral infection may be enhanced via the TF-protease axis.
许多病毒类型都会影响凝血系统,并与从血栓形成到大出血再到炎症等各种病理现象相关联。在此,我们将概述由宿主或病毒基因组编码的病毒蛋白质、凝血蛋白、血小板、白细胞和内皮细胞之间因感染而产生的错综复杂的相互影响。对于从宿主细胞获得外壳(包膜)的血源性病毒来说,病毒表面源自细胞的凝血触发因子--组织因子(TF)可能是一个关键角色。TF 是一种多功能跨膜辅助因子,可加速因子(F)VIIa 依赖性活化 FX 为 FXa,从而形成血凝块。不过,新生的 TF/FVIIa/FXa 复合物还能通过蛋白酶激活受体-2 促进 G 蛋白耦合调节细胞。作为一种病毒包膜成分,TF 可以绕过生理调节模式,从而激活邻近的血小板、白细胞和内皮细胞。细胞因子、促凝血蛋白和中性粒细胞胞外捕获物的细胞释放,以及刺激引起的粘附受体的可及性导致细胞聚集,由此产生的反馈放大作用预示着血栓性炎症环境的形成。血栓栓塞性炎症的病理生物学效应最终会促进先天性和适应性免疫,从而清除病毒。相反,病毒感染的前几个阶段可能会通过 TF 蛋白酶轴得到加强。
{"title":"Viral coagulation: pushing the envelope.","authors":"Edward Louis George Pryzdial, John Ruggles Perrier, Mahamud-Ur Rashid, Henry Euan West, Michael Ross Sutherland","doi":"10.1016/j.jtha.2024.08.014","DOIUrl":"10.1016/j.jtha.2024.08.014","url":null,"abstract":"<p><p>Many virus types affect the blood clotting system with correlations to pathology that range widely from thrombosis to hemorrhage linking to inflammation. Here we overview the intricate crosstalk induced by infection between proteins on the virus encoded by either the host or virus genomes, coagulation proteins, platelets, leukocytes, and endothelial cells. For blood-borne viruses with an outer covering acquired from the host cell, the envelope, a key player may be the cell-derived trigger of coagulation on the virus surface, tissue factor (TF). TF is a multifunctional transmembrane cofactor that accelerates factor (F)VIIa-dependent activation of FX to FXa, leading to clot formation. However, the nascent TF/FVIIa/FXa complex also facilitates G protein-coupled modulation of cells via protease-activated receptor 2. As a viral envelope constituent, TF can bypass the physiological modes of regulation, thereby initiating the activation of neighboring platelets, leukocytes, and endothelial cells. A thromboinflammatory environment is predicted due to feedback amplification in response to cellular release of cytokines, procoagulant proteins, neutrophil extracellular traps, and stimulus-induced accessibility of adhesive receptors, resulting in cellular aggregates. The pathobiological effects of thromboinflammation ultimately contribute to innate and adaptive immunity for viral clearance. In contrast, the preceding stages of viral infection may be enhanced via the TF-protease axis.</p>","PeriodicalId":17326,"journal":{"name":"Journal of Thrombosis and Haemostasis","volume":" ","pages":""},"PeriodicalIF":5.5,"publicationDate":"2024-09-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142289967","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}