首页 > 最新文献

Research and Practice in Thrombosis and Haemostasis最新文献

英文 中文
Antithrombotic therapy in lower extremity peripheral artery disease patients with venous thromboembolism: a nationwide cohort study 下肢外周动脉疾病伴静脉血栓栓塞患者的抗血栓治疗:一项全国性队列研究
IF 3.4 3区 医学 Q2 HEMATOLOGY Pub Date : 2026-01-01 DOI: 10.1016/j.rpth.2025.103291
Jamilla Goedegebuur , Elena Butera , Qingui Chen , Behnood Bikdeli , Walter Ageno , Roberto Pola , Angelo Porfidia , Stefano Barco , Thijs E. van Mens , Joost R. van der Vorst , Suzanne C. Cannegieter , Frederikus A. Klok

Background

Antithrombotic therapy (ATT) is recommended for patients with symptomatic lower extremity peripheral arterial disease (PAD). Optimal management of “breakthrough” venous thromboembolic events (VTEs) in these patients remains unclear. This study aims to describe current ATT prescription patterns in PAD patients before, during, and after VTE (treatment) and subsequent clinical outcomes.

Methods

Using Dutch nationwide data, this cohort study identified patients with a reimbursement code for PAD between 2013 and 2021. Within this source population, patients with an International Classification of Diseases-10 code for VTE were identified and followed from VTE date until end-of-study date or death, whichever occurred first. ATT prescriptions, determined from pharmacy records, were mapped in 3 timeframes: 3 months before VTE, during VTE treatment, and 4 to 12 months after VTE.

Results

Patients with PAD (N = 1866) and a concurrent VTE were included, with a mean age of 71.7 years and a median survival of 3.8 years. Before the VTE, 64% used antiplatelet therapy only, in contrast to 12% after VTE treatment. During the VTE treatment period, direct oral anticoagulants were the most frequently dispensed ATT type (40%), whereas 27% received anticoagulation plus antiplatelet therapy during this time. The one-year cumulative incidences of arterial thromboembolic events and clinically relevant bleedings were 6.1% (95% CI: 4.9-7.3) and 1.8% (95% CI, 1.2-2.4), respectively.

Conclusion

Immediate treatment of VTE and long-term ATT use in PAD patients were heterogeneous in our cohort. A substantial proportion of patients had prescriptions for both antiplatelet therapy and anticoagulation during the VTE treatment period. Our findings highlight the need for consensus on this complex clinical dilemma.
背景:抗血栓治疗(ATT)被推荐用于有症状的下肢外周动脉疾病(PAD)患者。这些患者的“突破性”静脉血栓栓塞事件(vte)的最佳管理仍不清楚。本研究旨在描述当前PAD患者在VTE(治疗)之前、期间和之后的ATT处方模式以及随后的临床结果。方法:使用荷兰全国数据,本队列研究确定了2013年至2021年间具有PAD报销代码的患者。在该源人群中,识别出具有国际疾病分类-10编码的静脉血栓栓塞患者,并从静脉血栓栓塞发生日期开始随访,直至研究结束日期或死亡,以先发生者为准。根据药房记录确定的ATT处方分为三个时间段:静脉血栓栓塞前3个月、静脉血栓栓塞治疗期间和静脉血栓栓塞后4至12个月。结果纳入PAD合并静脉血栓栓塞患者(N = 1866),平均年龄71.7岁,中位生存期3.8年。静脉血栓栓塞前,64%的患者仅使用抗血小板治疗,而静脉血栓栓塞治疗后,这一比例为12%。在静脉血栓栓塞治疗期间,直接口服抗凝剂是最常见的ATT型(40%),而27%的患者在此期间接受了抗凝+抗血小板治疗。动脉血栓栓塞事件和临床相关出血的一年累积发生率分别为6.1% (95% CI: 4.9-7.3)和1.8% (95% CI, 1.2-2.4)。结论:在我们的队列中,PAD患者立即治疗静脉血栓栓塞和长期使用静脉血栓栓塞存在异质性。相当比例的患者在静脉血栓栓塞治疗期间同时使用抗血小板治疗和抗凝治疗。我们的发现强调了在这个复杂的临床困境上达成共识的必要性。
{"title":"Antithrombotic therapy in lower extremity peripheral artery disease patients with venous thromboembolism: a nationwide cohort study","authors":"Jamilla Goedegebuur ,&nbsp;Elena Butera ,&nbsp;Qingui Chen ,&nbsp;Behnood Bikdeli ,&nbsp;Walter Ageno ,&nbsp;Roberto Pola ,&nbsp;Angelo Porfidia ,&nbsp;Stefano Barco ,&nbsp;Thijs E. van Mens ,&nbsp;Joost R. van der Vorst ,&nbsp;Suzanne C. Cannegieter ,&nbsp;Frederikus A. Klok","doi":"10.1016/j.rpth.2025.103291","DOIUrl":"10.1016/j.rpth.2025.103291","url":null,"abstract":"<div><h3>Background</h3><div>Antithrombotic therapy (ATT) is recommended for patients with symptomatic lower extremity peripheral arterial disease (PAD). Optimal management of “breakthrough” venous thromboembolic events (VTEs) in these patients remains unclear. This study aims to describe current ATT prescription patterns in PAD patients before, during, and after VTE (treatment) and subsequent clinical outcomes.</div></div><div><h3>Methods</h3><div>Using Dutch nationwide data, this cohort study identified patients with a reimbursement code for PAD between 2013 and 2021. Within this source population, patients with an International Classification of Diseases-10 code for VTE were identified and followed from VTE date until end-of-study date or death, whichever occurred first. ATT prescriptions, determined from pharmacy records, were mapped in 3 timeframes: 3 months before VTE, during VTE treatment, and 4 to 12 months after VTE.</div></div><div><h3>Results</h3><div>Patients with PAD (<em>N</em> = 1866) and a concurrent VTE were included, with a mean age of 71.7 years and a median survival of 3.8 years. Before the VTE, 64% used antiplatelet therapy only, in contrast to 12% after VTE treatment. During the VTE treatment period, direct oral anticoagulants were the most frequently dispensed ATT type (40%), whereas 27% received anticoagulation plus antiplatelet therapy during this time. The one-year cumulative incidences of arterial thromboembolic events and clinically relevant bleedings were 6.1% (95% CI: 4.9-7.3) and 1.8% (95% CI, 1.2-2.4), respectively.</div></div><div><h3>Conclusion</h3><div>Immediate treatment of VTE and long-term ATT use in PAD patients were heterogeneous in our cohort. A substantial proportion of patients had prescriptions for both antiplatelet therapy and anticoagulation during the VTE treatment period. Our findings highlight the need for consensus on this complex clinical dilemma.</div></div>","PeriodicalId":20893,"journal":{"name":"Research and Practice in Thrombosis and Haemostasis","volume":"10 1","pages":"Article 103291"},"PeriodicalIF":3.4,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145927166","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}
引用次数: 0
Mortality trends in patients with coexisting pulmonary embolism and obesity: a major public health concern 并发肺栓塞和肥胖患者的死亡率趋势:一个主要的公共卫生问题
IF 3.4 3区 医学 Q2 HEMATOLOGY Pub Date : 2026-01-01 DOI: 10.1016/j.rpth.2025.103338
Vânia M. Morelli
{"title":"Mortality trends in patients with coexisting pulmonary embolism and obesity: a major public health concern","authors":"Vânia M. Morelli","doi":"10.1016/j.rpth.2025.103338","DOIUrl":"10.1016/j.rpth.2025.103338","url":null,"abstract":"","PeriodicalId":20893,"journal":{"name":"Research and Practice in Thrombosis and Haemostasis","volume":"10 1","pages":"Article 103338"},"PeriodicalIF":3.4,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145978192","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}
引用次数: 0
Hetrombopag for the treatment of chemotherapy-induced thrombocytopenia in patients with solid tumors Hetrombopag用于治疗化疗引起的实体瘤患者血小板减少症
IF 3.4 3区 医学 Q2 HEMATOLOGY Pub Date : 2026-01-01 DOI: 10.1016/j.rpth.2025.103326
Yuan Liu , Bo Liu , Shan-Shan Fang , Run-Sheng Zhao , Lin Li , Hui-Xiong Qi , Quan Li
Based on real-world research, we aimed to systematically evaluate the efficacy and safety of hetrombopag for the treatment of chemotherapy-induced thrombocytopenia (CIT) in patients with solid tumors. Patients with solid tumors who developed CIT (platelet count < 100 × 109/L) and were treated with hetrombopag in a single hospital between February 2022 and September 2023 were included in the study. The primary outcome was complete response rate within 14 days, defined as the proportion of patients with platelet counts of ≥100 × 109/L or platelet counts increased by at least 50 × 109/L from baseline. Response rate within 21 days, the incidence of chemotherapy intensity reduction, the median time of response, and adverse events were reported. A total of 73 patients met the inclusion criteria and were subsequently included in the analysis. The complete response rate within 14 days was 79.5%. Within 21 days, the complete response rate was 91.8%. The incidence of chemotherapy intensity reduction was 21.9%. The median time to platelet response was 9.0 days (95% CI, 8.3-9.7 days). The baseline platelet count of ≥ 50 × 109/L and the treatment regimen of hetrombopag combined with rhTPO/rhIL-11 were identified as independent favorable prognostic factors for platelet response time. Subgroup analyses demonstrated that patients receiving combination regimen exhibited a significantly reduced median time to platelet response with baseline platelet counts of ≥50 × 109/L. Safety profile showed good tolerability of hetrombopag (monotherapy or combined with rhTPO/rhIL-11) in patients. Hetrombopag may be an effective and well-tolerated treatment option for CIT in patients with solid tumors.
基于现实世界的研究,我们旨在系统地评估hetrombopag治疗实体瘤患者化疗性血小板减少症(CIT)的有效性和安全性。研究纳入了2022年2月至2023年9月间在一家医院接受hetrombopag治疗的CIT(血小板计数<; 100 × 109/L)实体肿瘤患者。主要终点是14天内的完全缓解率,定义为血小板计数≥100 × 109/L或血小板计数较基线增加至少50 × 109/L的患者比例。报告21天内的缓解率、化疗强度降低的发生率、中位缓解时间和不良事件。共有73名患者符合纳入标准,随后被纳入分析。14天内完全缓解率为79.5%。在21天内,完全缓解率为91.8%。化疗强度降低发生率为21.9%。血小板应答的中位时间为9.0天(95% CI, 8.3-9.7天)。基线血小板计数≥50 × 109/L和hetrombopag联合rhTPO/rhIL-11治疗方案被确定为血小板反应时间的独立有利预后因素。亚组分析表明,当基线血小板计数≥50 × 109/L时,接受联合治疗的患者出现血小板反应的中位时间显著缩短。安全性分析显示,患者对hetrombopag(单药或与rhTPO/rhIL-11联合治疗)具有良好的耐受性。Hetrombopag可能是实体瘤患者CIT的有效且耐受性良好的治疗选择。
{"title":"Hetrombopag for the treatment of chemotherapy-induced thrombocytopenia in patients with solid tumors","authors":"Yuan Liu ,&nbsp;Bo Liu ,&nbsp;Shan-Shan Fang ,&nbsp;Run-Sheng Zhao ,&nbsp;Lin Li ,&nbsp;Hui-Xiong Qi ,&nbsp;Quan Li","doi":"10.1016/j.rpth.2025.103326","DOIUrl":"10.1016/j.rpth.2025.103326","url":null,"abstract":"<div><div>Based on real-world research, we aimed to systematically evaluate the efficacy and safety of hetrombopag for the treatment of chemotherapy-induced thrombocytopenia (CIT) in patients with solid tumors. Patients with solid tumors who developed CIT (platelet count &lt; 100 × 10<sup>9</sup>/L) and were treated with hetrombopag in a single hospital between February 2022 and September 2023 were included in the study. The primary outcome was complete response rate within 14 days, defined as the proportion of patients with platelet counts of ≥100 × 10<sup>9</sup>/L or platelet counts increased by at least 50 × 10<sup>9</sup>/L from baseline. Response rate within 21 days, the incidence of chemotherapy intensity reduction, the median time of response, and adverse events were reported. A total of 73 patients met the inclusion criteria and were subsequently included in the analysis. The complete response rate within 14 days was 79.5%. Within 21 days, the complete response rate was 91.8%. The incidence of chemotherapy intensity reduction was 21.9%. The median time to platelet response was 9.0 days (95% CI, 8.3-9.7 days). The baseline platelet count of ≥ 50 × 10<sup>9</sup>/L and the treatment regimen of hetrombopag combined with rhTPO/rhIL-11 were identified as independent favorable prognostic factors for platelet response time. Subgroup analyses demonstrated that patients receiving combination regimen exhibited a significantly reduced median time to platelet response with baseline platelet counts of ≥50 × 10<sup>9</sup>/L. Safety profile showed good tolerability of hetrombopag (monotherapy or combined with rhTPO/rhIL-11) in patients. Hetrombopag may be an effective and well-tolerated treatment option for CIT in patients with solid tumors.</div></div>","PeriodicalId":20893,"journal":{"name":"Research and Practice in Thrombosis and Haemostasis","volume":"10 1","pages":"Article 103326"},"PeriodicalIF":3.4,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146022848","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}
引用次数: 0
Tissue factor detection in mouse tissues by western blotting using commercial antibodies 利用商业抗体进行组织因子检测
IF 3.4 3区 医学 Q2 HEMATOLOGY Pub Date : 2026-01-01 DOI: 10.1016/j.rpth.2025.103336
Megan V. Perkins , Sierra J. Archibald , Ana T.A. Sachetto , Nigel Mackman

Background

Tissue factor (TF) is a receptor for factor (F)VII/FVIIa and is essential for hemostasis. TF is expressed in a tissue-specific manner, with differing TF levels across tissues. TF expression is increased in a variety of diseases, so accurate measurement of TF protein levels is important.

Objectives

The goal of this study was to evaluate the ability of 4 commercial antibodies to measure TF in various mouse tissues using western blotting.

Methods

We used the goat anti-mouse TF polyclonal antibody AF3178 (R&D Systems), the rabbit anti-mouse TF monoclonal antibody ab189483 (Abcam), the rabbit anti-mouse TF monoclonal antibody 44861 (Cell Signaling Technology), and the mouse anti-mouse TF monoclonal antibody H9 (Santa Cruz Biotechnology) to measure TF in the mouse pancreatic cancer cell line KPC2 wild-type and KPC2 TF knockout cell lysates, as well as various tissues from wild-type and low TF mice (no mouse TF expression) using western blotting.

Results

All 4 antibodies detected TF in KPC2 wild-type cells but not in KPC2 TF knockout cells. All 4 antibodies detected TF in the brain, lung, heart, kidney, and spleen. The relative amounts of TF in these tissues were consistent with the tissue distribution of TF mRNA reported in previous studies. Nonspecific bands were detected in various tissues with the different antibodies.

Conclusion

Our study demonstrated that the Abcam and Cell Signaling Technology anti-mouse TF monoclonal antibodies gave the strongest signal for TF in mouse tissues. However, researchers should be aware that all 4 antibodies also detect nonspecific bands in some tissues.
组织因子(TF)是因子(F)VII/FVIIa的受体,对止血至关重要。TF以组织特异性的方式表达,不同组织的TF水平不同。TF在多种疾病中表达增加,因此准确测量TF蛋白水平非常重要。目的本研究的目的是评估4种商业抗体在不同小鼠组织中使用western blotting检测TF的能力。方法采用山羊抗小鼠TF多克隆抗体AF3178 (R&D Systems)、兔抗小鼠TF单克隆抗体ab189483 (Abcam)、兔抗小鼠TF单克隆抗体44861 (Cell Signaling Technology)和小鼠抗小鼠TF单克隆抗体H9 (Santa Cruz Biotechnology)检测小鼠胰腺癌细胞系KPC2野生型和KPC2 TF敲除细胞裂解液中TF的含量。以及野生型和低TF小鼠(无小鼠TF表达)的各种组织。结果4种抗体均在KPC2野生型细胞中检测到TF,而在KPC2 TF敲除细胞中检测不到TF。所有4种抗体均在脑、肺、心、肾和脾中检测到TF。这些组织中TF的相对量与以往研究中报道的TF mRNA的组织分布一致。在不同抗体的不同组织中检测到非特异性条带。结论Abcam和Cell Signaling Technology抗小鼠TF单克隆抗体对TF在小鼠组织中的表达信号最强。然而,研究人员应该意识到,这4种抗体在某些组织中也能检测到非特异性条带。
{"title":"Tissue factor detection in mouse tissues by western blotting using commercial antibodies","authors":"Megan V. Perkins ,&nbsp;Sierra J. Archibald ,&nbsp;Ana T.A. Sachetto ,&nbsp;Nigel Mackman","doi":"10.1016/j.rpth.2025.103336","DOIUrl":"10.1016/j.rpth.2025.103336","url":null,"abstract":"<div><h3>Background</h3><div>Tissue factor (TF) is a receptor for factor (F)VII/FVIIa and is essential for hemostasis. TF is expressed in a tissue-specific manner, with differing TF levels across tissues. TF expression is increased in a variety of diseases, so accurate measurement of TF protein levels is important.</div></div><div><h3>Objectives</h3><div>The goal of this study was to evaluate the ability of 4 commercial antibodies to measure TF in various mouse tissues using western blotting.</div></div><div><h3>Methods</h3><div>We used the goat anti-mouse TF polyclonal antibody AF3178 (R&amp;D Systems), the rabbit anti-mouse TF monoclonal antibody ab189483 (Abcam), the rabbit anti-mouse TF monoclonal antibody 44861 (Cell Signaling Technology), and the mouse anti-mouse TF monoclonal antibody H9 (Santa Cruz Biotechnology) to measure TF in the mouse pancreatic cancer cell line KPC2 wild-type and KPC2 TF knockout cell lysates, as well as various tissues from wild-type and low TF mice (no mouse TF expression) using western blotting.</div></div><div><h3>Results</h3><div>All 4 antibodies detected TF in KPC2 wild-type cells but not in KPC2 TF knockout cells. All 4 antibodies detected TF in the brain, lung, heart, kidney, and spleen. The relative amounts of TF in these tissues were consistent with the tissue distribution of TF mRNA reported in previous studies. Nonspecific bands were detected in various tissues with the different antibodies.</div></div><div><h3>Conclusion</h3><div>Our study demonstrated that the Abcam and Cell Signaling Technology anti-mouse TF monoclonal antibodies gave the strongest signal for TF in mouse tissues. However, researchers should be aware that all 4 antibodies also detect nonspecific bands in some tissues.</div></div>","PeriodicalId":20893,"journal":{"name":"Research and Practice in Thrombosis and Haemostasis","volume":"10 1","pages":"Article 103336"},"PeriodicalIF":3.4,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146022851","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}
引用次数: 0
PAR for the course – protease-activated receptor 4 protects the brain from hemorrhage PAR的过程-蛋白酶激活受体4保护脑出血
IF 3.4 3区 医学 Q2 HEMATOLOGY Pub Date : 2026-01-01 DOI: 10.1016/j.rpth.2025.103337
Izabella Andrianova , Frederik Denorme
{"title":"PAR for the course – protease-activated receptor 4 protects the brain from hemorrhage","authors":"Izabella Andrianova ,&nbsp;Frederik Denorme","doi":"10.1016/j.rpth.2025.103337","DOIUrl":"10.1016/j.rpth.2025.103337","url":null,"abstract":"","PeriodicalId":20893,"journal":{"name":"Research and Practice in Thrombosis and Haemostasis","volume":"10 1","pages":"Article 103337"},"PeriodicalIF":3.4,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146022847","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}
引用次数: 0
Venous thromboembolism and 20-year cancer risk: a Danish population-based cohort study 静脉血栓栓塞和20年癌症风险:一项丹麦人群队列研究
IF 3.4 3区 医学 Q2 HEMATOLOGY Pub Date : 2026-01-01 DOI: 10.1016/j.rpth.2025.103318
Søren K. Martiny , Vincent Lanting , Dóra K. Farkas , Nick van Es , Henrik T. Sørensen

Background

Venous thromboembolism (VTE) is associated with an elevated short-term cancer risk, but data on the long-term risk are conflicting. The mechanisms linking patients with VTE to elevated long-term cancer risk remain largely unknown.

Objectives

To investigate long-term cancer risk after VTE and whether this risk pertained predominantly to cancers sharing risk factors with VTE.

Methods

Using nationwide Danish registries, we followed patients with first-time VTE (1996-2022) until cancer diagnosis, death, emigration, or December 31, 2022, whichever occurred first. We used the Aalen–Johansen estimator to compute cumulative cancer incidence, treating death as a competing event. Standardized incidence ratios (SIRs) compared observed events with expected events based on general population rates. We analyzed cancer incidence overall and by site-specific and etiology groups for smoking-, obesity-, alcohol-, hormone-, and infection-related cancers, and “all other” cancers.

Results

We followed 138,049 patients for a median of 5.5 years. The 1-year cancer risk was 4.0%. The 1-year SIR was 3.45 (95% CI, 3.36-3.55), then ranged from 1.09 to 1.16 over 20 years of follow-up, reaching 1.00 (95% CI, 0.90-1.11) thereafter. SIR was elevated in all cancer groups within 1 year and afterward, but was driven by site-specific cancers often related to smoking, obesity, and alcohol (lung, pharynx, larynx, esophagus, stomach, liver, pancreas, and colon), as well as hematological cancers.

Conclusion

Compared with the general population, patients with VTE had an increased cancer risk for up to 20 years. Shared risk factors, such as lifestyle-related factors and genetic predisposition, may contribute to this increased risk.
背景静脉血栓栓塞(VTE)与短期癌症风险升高有关,但长期风险的数据相互矛盾。静脉血栓栓塞患者与长期癌症风险升高之间的联系机制在很大程度上仍然未知。目的探讨静脉血栓栓塞术后的长期癌症风险,以及这种风险是否主要与静脉血栓栓塞有共同危险因素的癌症有关。方法使用丹麦全国范围内的登记处,我们对首次静脉血栓栓塞患者(1996-2022)进行随访,直到癌症诊断、死亡、移民或2022年12月31日,以先发生者为准。我们使用aallen - johansen估计器来计算累积癌症发病率,将死亡视为一个竞争事件。标准化发生率比(SIRs)将观察到的事件与基于一般人群发生率的预期事件进行比较。我们分析了吸烟、肥胖、酒精、激素和感染相关癌症以及“所有其他”癌症的总体发病率,并按部位特异性和病因组进行了分析。结果我们随访了138049例患者,中位时间为5.5年。1年癌症风险为4.0%。1年SIR为3.45 (95% CI, 3.36-3.55), 20年随访后SIR为1.09 - 1.16,随访后SIR为1.00 (95% CI, 0.90-1.11)。1年内及之后,所有癌症组的SIR均升高,但主要是由与吸烟、肥胖和酒精相关的部位特异性癌症(肺癌、咽喉癌、食道癌、胃癌、肝癌、胰腺癌和结肠癌)以及血液病引起的。结论与普通人群相比,静脉血栓栓塞患者在长达20年的时间内癌症风险增加。共同的风险因素,如生活方式相关因素和遗传易感性,可能会导致这种风险增加。
{"title":"Venous thromboembolism and 20-year cancer risk: a Danish population-based cohort study","authors":"Søren K. Martiny ,&nbsp;Vincent Lanting ,&nbsp;Dóra K. Farkas ,&nbsp;Nick van Es ,&nbsp;Henrik T. Sørensen","doi":"10.1016/j.rpth.2025.103318","DOIUrl":"10.1016/j.rpth.2025.103318","url":null,"abstract":"<div><h3>Background</h3><div>Venous thromboembolism (VTE) is associated with an elevated short-term cancer risk, but data on the long-term risk are conflicting. The mechanisms linking patients with VTE to elevated long-term cancer risk remain largely unknown.</div></div><div><h3>Objectives</h3><div>To investigate long-term cancer risk after VTE and whether this risk pertained predominantly to cancers sharing risk factors with VTE.</div></div><div><h3>Methods</h3><div>Using nationwide Danish registries, we followed patients with first-time VTE (1996-2022) until cancer diagnosis, death, emigration, or December 31, 2022, whichever occurred first. We used the Aalen–Johansen estimator to compute cumulative cancer incidence, treating death as a competing event. Standardized incidence ratios (SIRs) compared observed events with expected events based on general population rates. We analyzed cancer incidence overall and by site-specific and etiology groups for smoking-, obesity-, alcohol-, hormone-, and infection-related cancers, and “all other” cancers.</div></div><div><h3>Results</h3><div>We followed 138,049 patients for a median of 5.5 years. The 1-year cancer risk was 4.0%. The 1-year SIR was 3.45 (95% CI, 3.36-3.55), then ranged from 1.09 to 1.16 over 20 years of follow-up, reaching 1.00 (95% CI, 0.90-1.11) thereafter. SIR was elevated in all cancer groups within 1 year and afterward, but was driven by site-specific cancers often related to smoking, obesity, and alcohol (lung, pharynx, larynx, esophagus, stomach, liver, pancreas, and colon), as well as hematological cancers.</div></div><div><h3>Conclusion</h3><div>Compared with the general population, patients with VTE had an increased cancer risk for up to 20 years. Shared risk factors, such as lifestyle-related factors and genetic predisposition, may contribute to this increased risk.</div></div>","PeriodicalId":20893,"journal":{"name":"Research and Practice in Thrombosis and Haemostasis","volume":"10 1","pages":"Article 103318"},"PeriodicalIF":3.4,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146078267","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}
引用次数: 0
Comparison of changes in blood cells and hemostatic biomarkers in mouse xenograft models of acute myeloid leukemia and acute promyelocytic leukemia 急性髓细胞白血病和急性早幼粒细胞白血病小鼠异种移植模型中血细胞和止血生物标志物变化的比较
IF 3.4 3区 医学 Q2 HEMATOLOGY Pub Date : 2026-01-01 DOI: 10.1016/j.rpth.2025.103319
Sierra J. Archibald , Ana T.A. Sachetto , Xingru Zhu , Radhika Gangaraju , Nigel Mackman , Yohei Hisada

Background

Leukemia patients have an increased risk of both thrombosis and bleeding due to a dysregulated hemostatic system. Levels of coagulation and fibrinolysis activation markers are increased, whereas levels of platelets and fibrinogen are decreased in leukemia patients. Mouse models can be used to study the pathways that contribute to coagulopathy in leukemia.

Objectives

To measure blood cells and hemostatic biomarkers in a mouse xenograft model of acute myeloid leukemia (AML) and compare them with a mouse xenograft model of acute promyelocytic leukemia (APL).

Methods

We established a mouse xenograft model of AML by injecting HL-60-Luc2 cells into NOD.Cg-Prkdcscid Il2rgtm1Wjl/SzJ mice and monitored the growth of leukemic cells by measuring luciferase expression. Levels of blood cells and hemostatic biomarkers were measured in leukemic mice. The parameters of the AML model were compared with those of the APL model using NB4-Luc cells.

Results

AML mice exhibited an increase in white blood cells, an increase in a marker of coagulation activation (thrombin-antithrombin complexes), an increase in a marker of fibrinolysis activation (plasmin-antiplasmin complexes), and a decrease in platelets and fibrinogen compared with control mice. No increase in white blood cell counts was observed in APL mice. APL mice had significantly higher levels of thrombin-antithrombin complexes compared with AML mice.

Conclusion

These leukemia mouse models can be used to understand how the hemostatic system is dysregulated in leukemia.
背景:由于止血系统失调,白血病患者血栓和出血的风险增加。白血病患者凝血和纤溶激活标志物水平升高,而血小板和纤维蛋白原水平降低。小鼠模型可用于研究导致白血病凝血功能障碍的途径。目的测定小鼠急性髓性白血病(AML)移植模型的血细胞和止血生物标志物,并与小鼠急性早幼粒细胞白血病(APL)移植模型进行比较。方法将HL-60-Luc2细胞注入NOD,建立小鼠AML异种移植模型。g- prkdcscid Il2rgtm1Wjl/SzJ小鼠,通过荧光素酶的表达监测白血病细胞的生长。在白血病小鼠中测量血细胞和止血生物标志物的水平。利用NB4-Luc细胞将AML模型与APL模型的参数进行比较。结果与对照组小鼠相比,saml小鼠表现出白细胞增加,凝血激活标志物(凝血酶-抗凝血酶复合物)增加,纤维蛋白溶解激活标志物(纤溶酶-抗纤溶酶复合物)增加,血小板和纤维蛋白原减少。APL小鼠的白细胞计数未见增加。APL小鼠的凝血酶-抗凝血酶复合物水平明显高于AML小鼠。结论这些模型可用于了解白血病小鼠止血系统失调的机制。
{"title":"Comparison of changes in blood cells and hemostatic biomarkers in mouse xenograft models of acute myeloid leukemia and acute promyelocytic leukemia","authors":"Sierra J. Archibald ,&nbsp;Ana T.A. Sachetto ,&nbsp;Xingru Zhu ,&nbsp;Radhika Gangaraju ,&nbsp;Nigel Mackman ,&nbsp;Yohei Hisada","doi":"10.1016/j.rpth.2025.103319","DOIUrl":"10.1016/j.rpth.2025.103319","url":null,"abstract":"<div><h3>Background</h3><div>Leukemia patients have an increased risk of both thrombosis and bleeding due to a dysregulated hemostatic system. Levels of coagulation and fibrinolysis activation markers are increased, whereas levels of platelets and fibrinogen are decreased in leukemia patients. Mouse models can be used to study the pathways that contribute to coagulopathy in leukemia.</div></div><div><h3>Objectives</h3><div>To measure blood cells and hemostatic biomarkers in a mouse xenograft model of acute myeloid leukemia (AML) and compare them with a mouse xenograft model of acute promyelocytic leukemia (APL).</div></div><div><h3>Methods</h3><div>We established a mouse xenograft model of AML by injecting HL-60-Luc2 cells into NOD.Cg-<em>Prkdc</em><sup><em>scid</em></sup> <em>Il2rg</em><sup><em>tm1Wjl</em></sup>/SzJ mice and monitored the growth of leukemic cells by measuring luciferase expression. Levels of blood cells and hemostatic biomarkers were measured in leukemic mice. The parameters of the AML model were compared with those of the APL model using NB4-Luc cells.</div></div><div><h3>Results</h3><div>AML mice exhibited an increase in white blood cells, an increase in a marker of coagulation activation (thrombin-antithrombin complexes), an increase in a marker of fibrinolysis activation (plasmin-antiplasmin complexes), and a decrease in platelets and fibrinogen compared with control mice. No increase in white blood cell counts was observed in APL mice. APL mice had significantly higher levels of thrombin-antithrombin complexes compared with AML mice.</div></div><div><h3>Conclusion</h3><div>These leukemia mouse models can be used to understand how the hemostatic system is dysregulated in leukemia.</div></div>","PeriodicalId":20893,"journal":{"name":"Research and Practice in Thrombosis and Haemostasis","volume":"10 1","pages":"Article 103319"},"PeriodicalIF":3.4,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145978123","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}
引用次数: 0
Factor VII deficiency is more prevalent than previously reported 因子七缺乏症比以前报道的更为普遍
IF 3.4 3区 医学 Q2 HEMATOLOGY Pub Date : 2026-01-01 DOI: 10.1016/j.rpth.2025.103284
Lukas Löwing Svensson , Elisabeth Aardal , Margareta Holmström

Background

The prevalence of factor (F)VII deficiency is estimated at approximately 1 of 500,000 individuals. However, low FVII activity (FVII:C) is frequently observed in a population of <500,000 in the region of Östergötland, Sweden.

Objectives

To estimate the prevalence and bleeding tendency of adult FVII-deficient patients in Östergötland, Sweden.

Methods

In this retrospective cross-sectional study, the laboratory information system was used to identify adult patients with at least one FVII:C result ≤ 0.50 kilo International Units per Liter (kIU/L) between January 1, 2017, and December 31, 2022. The most likely cause was established, and in patients with a FVII deficiency, as defined by the Nordic Hemophilia Council (FVII:C < 0.35 kIU/L) or low FVII level (0.35-0.50 kIU/L), the bleeding tendency was evaluated.

Results

FVII:C ≤ 0.50 kIU/L was identified in 97 patients residing in Östergötland. Of these, 21 had FVII deficiency, and 39 had low FVII level, corresponding to a prevalence of at least 1 of 17,800 and 1 of 9600 in the adult population in Östergötland, respectively. Patients with FVII deficiency differed significantly from patients with low FVII level in bleeding symptoms (P = .01). Of the FVII-deficient patients, 38% were asymptomatic, while 19% and 24% had experienced minor and major spontaneous bleedings, respectively.

Conclusion

The prevalence of FVII deficiency was estimated to be at least 1 of 17,800 adults, which is 28 times higher than the internationally claimed prevalence. Spontaneous bleeding occurred in 43% of these individuals.
据估计,因子(F)VII缺乏症的患病率约为50万人中的1人。然而,在瑞典Östergötland地区的50万人口中,经常观察到低FVII活性(FVII:C)。目的了解瑞典Östergötland地区成人fvii缺乏患者的患病率和出血倾向。方法在这项回顾性横断面研究中,使用实验室信息系统识别2017年1月1日至2022年12月31日期间至少有一项FVII:C结果≤0.50 kg国际单位/升(kIU/L)的成年患者。确定了最可能的原因,并对北欧血友病委员会定义的FVII缺乏(FVII:C < 0.35 kIU/L)或低FVII水平(0.35-0.50 kIU/L)的患者进行出血倾向评估。结果fvii:居住在Östergötland的97例患者C≤0.50 kIU/L。其中,21人有FVII缺乏,39人有低FVII水平,分别对应于Östergötland成年人口中17,800人中至少有1人和9600人中至少有1人的患病率。FVII缺乏患者与低FVII患者出血症状差异有统计学意义(P = 0.01)。在fvii缺乏的患者中,38%无症状,19%和24%分别出现轻微和严重自发性出血。结论FVII缺乏症的患病率估计在17800名成年人中至少有1人,比国际上声称的患病率高28倍。其中43%的人发生自发性出血。
{"title":"Factor VII deficiency is more prevalent than previously reported","authors":"Lukas Löwing Svensson ,&nbsp;Elisabeth Aardal ,&nbsp;Margareta Holmström","doi":"10.1016/j.rpth.2025.103284","DOIUrl":"10.1016/j.rpth.2025.103284","url":null,"abstract":"<div><h3>Background</h3><div>The prevalence of factor (F)VII deficiency is estimated at approximately 1 of 500,000 individuals. However, low FVII activity (FVII:C) is frequently observed in a population of &lt;500,000 in the region of Östergötland, Sweden.</div></div><div><h3>Objectives</h3><div>To estimate the prevalence and bleeding tendency of adult FVII-deficient patients in Östergötland, Sweden.</div></div><div><h3>Methods</h3><div>In this retrospective cross-sectional study, the laboratory information system was used to identify adult patients with at least one FVII:C result ≤ 0.50 kilo International Units per Liter (kIU/L) between January 1, 2017, and December 31, 2022. The most likely cause was established, and in patients with a FVII deficiency, as defined by the Nordic Hemophilia Council (FVII:C &lt; 0.35 kIU/L) or low FVII level (0.35-0.50 kIU/L), the bleeding tendency was evaluated.</div></div><div><h3>Results</h3><div>FVII:C ≤ 0.50 kIU/L was identified in 97 patients residing in Östergötland. Of these, 21 had FVII deficiency, and 39 had low FVII level, corresponding to a prevalence of at least 1 of 17,800 and 1 of 9600 in the adult population in Östergötland, respectively. Patients with FVII deficiency differed significantly from patients with low FVII level in bleeding symptoms (<em>P</em> = .01). Of the FVII-deficient patients, 38% were asymptomatic, while 19% and 24% had experienced minor and major spontaneous bleedings, respectively.</div></div><div><h3>Conclusion</h3><div>The prevalence of FVII deficiency was estimated to be at least 1 of 17,800 adults, which is 28 times higher than the internationally claimed prevalence. Spontaneous bleeding occurred in 43% of these individuals.</div></div>","PeriodicalId":20893,"journal":{"name":"Research and Practice in Thrombosis and Haemostasis","volume":"10 1","pages":"Article 103284"},"PeriodicalIF":3.4,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145885068","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}
引用次数: 0
Joint tissue plasticity in hemophilia: insights from the Joint Activity and Damage Exam ultrasound protocol 血友病的关节组织可塑性:来自关节活动和损伤检查超声协议的见解
IF 3.4 3区 医学 Q2 HEMATOLOGY Pub Date : 2026-01-01 DOI: 10.1016/j.rpth.2025.103290
Parthiv Sheth , Khang Tong , Bilgimol Chumappumkal Joseph , Tina Manon-Jensen , Michael Glenzer , Isaac Nwi-Mozu , Peter Aguero , Bruno Steiner , Cindy Bailey , Doris V. Quon , Rebecca Kruse-Jarres , Euyhyun Lee , Morten Asser Karsdal , Lin Liu , Annette von Drygalski

Background

Progressive arthropathy is a debilitating condition that affects hemophilic joints as a consequence of hemarthroses. However, our understanding of the trajectory of potentially destructive processes at the tissue level remains limited and requires longitudinal imaging studies.

Objectives

To longitudinally characterize ultrasonographic joint tissue changes in adults with hemophilia using the Joint Activity and Damage Exam (JADE) protocol, and to examine their relationships with joint health status, hemarthrosis, and serum biomarkers of tissue turnover.

Methods

We prospectively studied adults with hemophilia (A or B) of any severity and associated arthropathy at 3 North American sites. We assessed joint health using the Hemophilia Joint Health Score (HJHS) and musculoskeletal ultrasound, as well as the Joint Activity and Damage Exam protocol for direct measurements of osteochondral alterations, cartilage, and soft tissue in the elbows, ankles, and knees at study entry and at ∼12 to 18 and ∼24 to 36 months thereafter. Reported hemarthrosis between study visits was verified by musculoskeletal ultrasound. We analyzed tissue rate changes in healthy (HJHS 0-3) and unhealthy (HJHS ≥ 4) joints, as well as in joints with and without hemarthrosis. Associations between tissue measurements and serially obtained serum biomarkers (C4M, PRO-C4, and C3M) were explored using logistic regression.

Results

The median age (N = 44) was 36.5 years. Joints (133 healthy and 131 unhealthy at baseline) were evaluated serially. Only 16 joints experienced at least 1 hemarthrosis. At baseline, unhealthy joints had significantly thinner cartilage and increased osteochondral alterations and soft tissue swelling (all P values < .001). While individual joint tissues followed either a positive or negative trajectory of expansion or contraction over the ensuing 2 to 3 years, mean rate changes were not significantly different between healthy and unhealthy joints. Hemarthrosis resulted in a predilection for cartilage thinning and positive rate changes in PRO-C4 (P = .006).

Conclusion

Ultrasonographic tissue measurements discriminated between healthy and unhealthy joints at baseline. Measurements revealed a dynamic pattern of tissue plasticity not only in healthy but also in unhealthy and bleeding joints, suggesting potential for reversibility of often-assumed irreversible intra-articular damage in hemophilic joints.
背景:进行性关节病是血肿引起的血友病关节的衰弱性疾病。然而,我们对组织水平潜在破坏性过程的轨迹的理解仍然有限,需要纵向成像研究。目的利用关节活动和损伤检查(JADE)方案纵向表征成人血友病患者的超声关节组织变化,并探讨其与关节健康状况、血肿和组织转换的血清生物标志物的关系。方法:我们前瞻性地研究了北美3个地区任何严重程度的血友病(A或B)和相关关节病的成人患者。我们使用血友病关节健康评分(HJHS)和肌肉骨骼超声,以及关节活动和损伤检查方案来评估关节健康,直接测量研究开始时以及研究开始后12至18个月和24至36个月肘部、脚踝和膝盖的骨软骨改变、软骨和软组织。研究访问之间报告的关节血肿通过肌肉骨骼超声证实。我们分析了健康(HJHS 0-3)和不健康(HJHS≥4)关节以及有和不存在关节血肿的关节的组织率变化。使用逻辑回归探讨组织测量与连续获得的血清生物标志物(C4M, PRO-C4和C3M)之间的关联。结果中位年龄(N = 44)为36.5岁。关节(133个健康和131个不健康的基线)被连续评估。只有16个关节出现至少1次关节出血。在基线时,不健康关节的软骨明显变薄,骨软骨改变和软组织肿胀增加(P值均为0.01)。尽管个体关节组织在随后的2 - 3年里呈正或负的扩张或收缩轨迹,但健康和不健康关节之间的平均速率变化没有显著差异。关节出血导致软骨变薄的倾向和PRO-C4的阳性率变化(P = 0.006)。结论超声组织测量可区分健康和不健康关节的基线值。测量结果显示,不仅在健康关节中,在不健康关节和出血关节中也存在组织可塑性的动态模式,这表明血友病关节中通常被认为是不可逆的关节内损伤具有可逆性。
{"title":"Joint tissue plasticity in hemophilia: insights from the Joint Activity and Damage Exam ultrasound protocol","authors":"Parthiv Sheth ,&nbsp;Khang Tong ,&nbsp;Bilgimol Chumappumkal Joseph ,&nbsp;Tina Manon-Jensen ,&nbsp;Michael Glenzer ,&nbsp;Isaac Nwi-Mozu ,&nbsp;Peter Aguero ,&nbsp;Bruno Steiner ,&nbsp;Cindy Bailey ,&nbsp;Doris V. Quon ,&nbsp;Rebecca Kruse-Jarres ,&nbsp;Euyhyun Lee ,&nbsp;Morten Asser Karsdal ,&nbsp;Lin Liu ,&nbsp;Annette von Drygalski","doi":"10.1016/j.rpth.2025.103290","DOIUrl":"10.1016/j.rpth.2025.103290","url":null,"abstract":"<div><h3>Background</h3><div>Progressive arthropathy is a debilitating condition that affects hemophilic joints as a consequence of hemarthroses. However, our understanding of the trajectory of potentially destructive processes at the tissue level remains limited and requires longitudinal imaging studies.</div></div><div><h3>Objectives</h3><div>To longitudinally characterize ultrasonographic joint tissue changes in adults with hemophilia using the Joint Activity and Damage Exam (JADE) protocol, and to examine their relationships with joint health status, hemarthrosis, and serum biomarkers of tissue turnover.</div></div><div><h3>Methods</h3><div>We prospectively studied adults with hemophilia (A or B) of any severity and associated arthropathy at 3 North American sites. We assessed joint health using the Hemophilia Joint Health Score (HJHS) and musculoskeletal ultrasound, as well as the Joint Activity and Damage Exam protocol for direct measurements of osteochondral alterations, cartilage, and soft tissue in the elbows, ankles, and knees at study entry and at ∼12 to 18 and ∼24 to 36 months thereafter. Reported hemarthrosis between study visits was verified by musculoskeletal ultrasound. We analyzed tissue rate changes in healthy (HJHS 0-3) and unhealthy (HJHS ≥ 4) joints, as well as in joints with and without hemarthrosis. Associations between tissue measurements and serially obtained serum biomarkers (C4M, PRO-C4, and C3M) were explored using logistic regression.</div></div><div><h3>Results</h3><div>The median age (<em>N</em> = 44) was 36.5 years. Joints (133 healthy and 131 unhealthy at baseline) were evaluated serially. Only 16 joints experienced at least 1 hemarthrosis. At baseline, unhealthy joints had significantly thinner cartilage and increased osteochondral alterations and soft tissue swelling (all <em>P</em> values &lt; .001). While individual joint tissues followed either a positive or negative trajectory of expansion or contraction over the ensuing 2 to 3 years, mean rate changes were not significantly different between healthy and unhealthy joints. Hemarthrosis resulted in a predilection for cartilage thinning and positive rate changes in PRO-C4 (<em>P</em> = .006).</div></div><div><h3>Conclusion</h3><div>Ultrasonographic tissue measurements discriminated between healthy and unhealthy joints at baseline. Measurements revealed a dynamic pattern of tissue plasticity not only in healthy but also in unhealthy and bleeding joints, suggesting potential for reversibility of often-assumed irreversible intra-articular damage in hemophilic joints.</div></div>","PeriodicalId":20893,"journal":{"name":"Research and Practice in Thrombosis and Haemostasis","volume":"10 1","pages":"Article 103290"},"PeriodicalIF":3.4,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145885113","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}
引用次数: 0
Predicting venous thromboembolism risk from endogenous thrombin potential-based normalized activated protein C sensitivity ratio assay: toward early assessment of combined oral contraceptives 内源性凝血酶电位为基础的标准化活化蛋白C敏感性比测定预测静脉血栓栓塞风险:对联合口服避孕药的早期评估
IF 3.4 3区 医学 Q2 HEMATOLOGY Pub Date : 2026-01-01 DOI: 10.1016/j.rpth.2025.103285
Laure Morimont , Mitchell D. Creinin , Ulysse Gaspard , Jean-Michel Foidart , Jonathan Douxfils

Background

Combined oral contraceptives (COCs) increase venous thromboembolism (VTE) risk, depending on estrogen type, dose, and progestin. While epidemiological studies provide insight into these risks, they require years to complete. The normalized activated protein C sensitivity ratio (nAPCsr), a standardized assay of acquired activated protein C resistance, has emerged as a potential biomarker of COC-induced VTE risk.

Objectives

To develop a population-based in silico model predicting VTE risk associated with various COC formulations based on their mean nAPCsr values.

Methods

We analyzed 200 plasma samples from non-COC users and 257 from users of 9 different COCs. We constructed an exponential model to correlate the mean nAPCsr of 5 COCs with their available population-based VTE relative risk, as extracted from a published meta-analysis. We assessed model performance using R2, Spearman’s rank correlation coefficient, and the root mean square error, and performed a sensitivity analysis by excluding COC nonusers. We then estimated population-based VTE risks for the 4 COCs not used in model construction.

Results

The model demonstrated high predictive accuracy (R2 = .96; root mean square error = 0.21; Spearman correlation coefficient = 1) and remained robust despite group size imbalance. Predicted VTE risks for ethinylestradiol 30 μg with dienogest 2 mg, ethinylestradiol 20 μg with drospirenone 3 mg, estradiol 1.5 mg with nomegestrol acetate 2.5 mg, and estetrol 15 mg with drospirenone 3 mg were 4.36, 3.43, 1.50, and 1.45, respectively, consistent with or complementary to existing epidemiological evidence.

Conclusion

Our model, based on mean nAPCsr, provides a reliable, biomarker-based approach for predicting population-based COC-related VTE risk. This strategy could help shorten the time between product launch and population-based risk assessment.
背景:复方口服避孕药(COCs)会增加静脉血栓栓塞(VTE)的风险,这取决于雌激素的类型、剂量和黄体酮。虽然流行病学研究提供了对这些风险的深入了解,但它们需要数年才能完成。标准化活化蛋白C敏感性比(nAPCsr)是一种获得性活化蛋白C抗性的标准化测定方法,已成为coc诱导的静脉血栓栓塞风险的潜在生物标志物。目的建立基于人群的计算机模型,根据不同COC配方的平均nAPCsr值预测静脉血栓栓塞风险。方法对200例非coc使用者和257例9种不同coc使用者的血浆样本进行分析。我们构建了一个指数模型,将5种COCs的平均nAPCsr与其基于人群的静脉血栓栓塞相对风险联系起来,该数据来自一项已发表的荟萃分析。我们使用R2、Spearman等级相关系数和均方根误差来评估模型的性能,并通过排除COC非用户进行敏感性分析。然后,我们估计了未用于模型构建的4种COCs的基于人群的静脉血栓栓塞风险。结果该模型具有较高的预测准确率(R2 = 0.96,均方根误差= 0.21,Spearman相关系数= 1),且在群体规模不平衡的情况下仍具有稳健性。炔雌醇30 μg与双炔雌酮2 mg、炔雌醇20 μg与屈螺酮3 mg、雌二醇1.5 mg与醋酸异孕酮2.5 mg、雌二醇15 mg与屈螺酮3 mg的静脉血栓栓塞风险预测分别为4.36、3.43、1.50和1.45,与现有流行病学证据一致或互补。我们的模型基于平均nAPCsr,为预测基于人群的coc相关静脉血栓栓塞风险提供了可靠的、基于生物标志物的方法。这一策略有助于缩短产品发布和基于人群的风险评估之间的时间。
{"title":"Predicting venous thromboembolism risk from endogenous thrombin potential-based normalized activated protein C sensitivity ratio assay: toward early assessment of combined oral contraceptives","authors":"Laure Morimont ,&nbsp;Mitchell D. Creinin ,&nbsp;Ulysse Gaspard ,&nbsp;Jean-Michel Foidart ,&nbsp;Jonathan Douxfils","doi":"10.1016/j.rpth.2025.103285","DOIUrl":"10.1016/j.rpth.2025.103285","url":null,"abstract":"<div><h3>Background</h3><div>Combined oral contraceptives (COCs) increase venous thromboembolism (VTE) risk, depending on estrogen type, dose, and progestin. While epidemiological studies provide insight into these risks, they require years to complete. The normalized activated protein C sensitivity ratio (nAPCsr), a standardized assay of acquired activated protein C resistance, has emerged as a potential biomarker of COC-induced VTE risk.</div></div><div><h3>Objectives</h3><div>To develop a population-based <em>in silico</em> model predicting VTE risk associated with various COC formulations based on their mean nAPCsr values.</div></div><div><h3>Methods</h3><div>We analyzed 200 plasma samples from non-COC users and 257 from users of 9 different COCs. We constructed an exponential model to correlate the mean nAPCsr of 5 COCs with their available population-based VTE relative risk, as extracted from <em>a published</em> meta-analysis. We assessed model performance using <em>R</em><sup>2</sup>, Spearman’s rank correlation coefficient, and the root mean square error, and performed a sensitivity analysis by excluding COC nonusers. We then estimated population-based VTE risks for the 4 COCs not used in model construction.</div></div><div><h3>Results</h3><div>The model demonstrated high predictive accuracy (R<sup>2</sup> = .96; root mean square error = 0.21; Spearman correlation coefficient = 1) and remained robust despite group size imbalance. Predicted VTE risks for ethinylestradiol 30 μg with dienogest 2 mg, ethinylestradiol 20 μg with drospirenone 3 mg, estradiol 1.5 mg with nomegestrol acetate 2.5 mg, and estetrol 15 mg with drospirenone 3 mg were 4.36, 3.43, 1.50, and 1.45, respectively, consistent with or complementary to existing epidemiological evidence.</div></div><div><h3>Conclusion</h3><div>Our model, based on mean nAPCsr, provides a reliable, biomarker-based approach for predicting population-based COC-related VTE risk. This strategy could help shorten the time between product launch and population-based risk assessment.</div></div>","PeriodicalId":20893,"journal":{"name":"Research and Practice in Thrombosis and Haemostasis","volume":"10 1","pages":"Article 103285"},"PeriodicalIF":3.4,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145978124","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}
引用次数: 0
期刊
Research and Practice in Thrombosis and Haemostasis
全部 Acc. Chem. Res. ACS Applied Bio Materials ACS Appl. Electron. Mater. ACS Appl. Energy Mater. ACS Appl. Mater. Interfaces ACS Appl. Nano Mater. ACS Appl. Polym. Mater. ACS BIOMATER-SCI ENG ACS Catal. ACS Cent. Sci. ACS Chem. Biol. ACS Chemical Health & Safety ACS Chem. Neurosci. ACS Comb. Sci. ACS Earth Space Chem. ACS Energy Lett. ACS Infect. Dis. ACS Macro Lett. ACS Mater. Lett. ACS Med. Chem. Lett. ACS Nano ACS Omega ACS Photonics ACS Sens. ACS Sustainable Chem. Eng. ACS Synth. Biol. Anal. Chem. BIOCHEMISTRY-US Bioconjugate Chem. BIOMACROMOLECULES Chem. Res. Toxicol. Chem. Rev. Chem. Mater. CRYST GROWTH DES ENERG FUEL Environ. Sci. Technol. Environ. Sci. Technol. Lett. Eur. J. Inorg. Chem. IND ENG CHEM RES Inorg. Chem. J. Agric. Food. Chem. J. Chem. Eng. Data J. Chem. Educ. J. Chem. Inf. Model. J. Chem. Theory Comput. J. Med. Chem. J. Nat. Prod. J PROTEOME RES J. Am. Chem. Soc. LANGMUIR MACROMOLECULES Mol. Pharmaceutics Nano Lett. Org. Lett. ORG PROCESS RES DEV ORGANOMETALLICS J. Org. Chem. J. Phys. Chem. J. Phys. Chem. A J. Phys. Chem. B J. Phys. Chem. C J. Phys. Chem. Lett. Analyst Anal. Methods Biomater. Sci. Catal. Sci. Technol. Chem. Commun. Chem. Soc. Rev. CHEM EDUC RES PRACT CRYSTENGCOMM Dalton Trans. Energy Environ. Sci. ENVIRON SCI-NANO ENVIRON SCI-PROC IMP ENVIRON SCI-WAT RES Faraday Discuss. Food Funct. Green Chem. Inorg. Chem. Front. Integr. Biol. J. Anal. At. Spectrom. J. Mater. Chem. A J. Mater. Chem. B J. Mater. Chem. C Lab Chip Mater. Chem. Front. Mater. Horiz. MEDCHEMCOMM Metallomics Mol. Biosyst. Mol. Syst. Des. Eng. Nanoscale Nanoscale Horiz. Nat. Prod. Rep. New J. Chem. Org. Biomol. Chem. Org. Chem. Front. PHOTOCH PHOTOBIO SCI PCCP Polym. Chem.
×
引用
GB/T 7714-2015
复制
MLA
复制
APA
复制
导出至
BibTeX EndNote RefMan NoteFirst NoteExpress
×
0
微信
客服QQ
Book学术公众号 扫码关注我们
反馈
×
意见反馈
请填写您的意见或建议
请填写您的手机或邮箱
×
提示
您的信息不完整,为了账户安全,请先补充。
现在去补充
×
提示
您因"违规操作"
具体请查看互助需知
我知道了
×
提示
现在去查看 取消
×
提示
确定
Book学术官方微信
Book学术文献互助
Book学术文献互助群
群 号:604180095
Book学术
文献互助 智能选刊 最新文献 互助须知 联系我们:info@booksci.cn
Book学术提供免费学术资源搜索服务,方便国内外学者检索中英文文献。致力于提供最便捷和优质的服务体验。
Copyright © 2023 Book学术 All rights reserved.
ghs 京公网安备 11010802042870号 京ICP备2023020795号-1