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Tocilizumab reduces hypercoagulation in COVID-19 – Perspectives from the coagulation and immunomodulation Covid assessment (Coag-ImmCovA) clinical trial 托昔单抗在 COVID-19 中降低了高凝状态--凝血和免疫调节 Covid 评估(Coag-ImmCovA)临床试验的观点
IF 3.7 3区 医学 Q1 HEMATOLOGY Pub Date : 2024-08-30 DOI: 10.1016/j.thromres.2024.109135
Lou M. Almskog , Anna Sjöström , Jonas Sundén-Cullberg , Apostolos Taxiarchis , Anna Ågren , Sara Freyland , Madeleine Börjesson , Agneta Wikman , Carl Magnus Wahlgren , Michael Wanecek , Jan van der Linden , Jovan Antovic , Jon Lampa , Maria Magnusson

Background

Despite medical interventions, COVID-19 continues to persist at pandemic proportions. A hypercoagulation state was rapidly observed in the severely ill, and the incidence of thromboembolic events remains elevated. Interleukin inhibitors have demonstrated positive effects on the hyperactivation of the immune system in COVID-19, with the interleukin-6 inhibitor tocilizumab showing promising results in reducing mortality. Nevertheless, the impact of interleukin inhibitors on the coagulation system remains incompletely understood.

Methods

In this clinical trial conducted in Stockholm, Sweden, interleukin inhibitors, namely anakinra (ANA) or tocilizumab (TOCI), were randomly administered in addition to standard care (SC) to hospitalized patients with COVID-19. A control group received only SC. The primary outcome sought to measure effects on global hemostasis, as indicated by changes in functional coagulation tests, specifically Rotational Thromboelastometry (ROTEM) or Overall Hemostatic Potential (OHP), visualized through scanning electron microscopy images. Secondary outcomes included effects on conventional coagulation laboratory tests.

Results

The study enrolled 74 patients who were randomized to receive either ANA or TOCI in addition to SC, or SC alone. In the TOCI group, ROTEM variables exhibited less hypercoagulation after 29 days compared with ANA or SC treatment groups, characterized by prolonged clot formation time and decreased clot firmness. OHP decreased, but there were no significant differences among the three treatment groups. Plasma fibrinogen levels, initially elevated, decreased significantly in TOCI recipients over time.

Conclusion

Tocilizumab treatment demonstrated a significant reduction of hypercoagulation in hospitalized COVID-19 patients, by improvements in both global coagulation tests and conventional laboratory tests, in comparison with anakinra or SC alone. This finding underscores the significance of tocilizumab as a viable treatment option in severe COVID-19 cases, with the potential to decrease thrombosis incidence.

背景尽管采取了医疗干预措施,但 COVID-19 仍在大范围流行。在重症患者中迅速观察到高凝状态,血栓栓塞事件的发生率仍然很高。白细胞介素抑制剂对 COVID-19 免疫系统的过度激活有积极作用,其中白细胞介素-6 抑制剂托西珠单抗在降低死亡率方面显示出良好效果。方法 在瑞典斯德哥尔摩进行的这项临床试验中,住院的 COVID-19 患者除了接受标准护理(SC)外,还随机使用白细胞介素抑制剂,即安那金拉(ANA)或托珠单抗(TOCI)。对照组仅接受SC治疗。主要结果旨在衡量对整体止血的影响,具体表现为功能性凝血测试的变化,特别是通过扫描电子显微镜图像观察到的旋转血栓弹性测定法(ROTEM)或整体止血电位(OHP)的变化。次要结果包括对常规凝血实验室测试的影响。结果该研究共招募了 74 名患者,随机分配他们在接受 SC 治疗的同时接受 ANA 或 TOCI 治疗,或仅接受 SC 治疗。与 ANA 或 SC 治疗组相比,TOCI 组的 ROTEM 变量在 29 天后显示出较低的高凝状态,其特点是凝块形成时间延长,凝块坚固性降低。OHP 下降,但三个治疗组之间没有显著差异。结论与单用 ANA 或 SC 相比,通过全面凝血检测和常规实验室检测的改善,Tocilizumab 治疗显著降低了 COVID-19 住院患者的高凝状态。这一发现强调了托西珠单抗作为重症COVID-19病例可行治疗方案的重要性,并有望降低血栓形成的发生率。
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引用次数: 0
TO INFORM OR NOT TO INFORM about venous thromboembolisms – A qualitative study on communication between healthcare professionals and patients with lung cancer 告知或不告知静脉血栓栓塞症--关于医护人员与肺癌患者之间沟通的定性研究
IF 3.7 3区 医学 Q1 HEMATOLOGY Pub Date : 2024-08-30 DOI: 10.1016/j.thromres.2024.109132
Camilla Berggreen , Jonas Hermann Schrøder , Thomas Christensen , Weronika Maria Szejniuk , Mette Søgaard , Anette Arbjerg Højen , Lone Jørgensen

Background

Venous thromboembolism (VTE) is a leading cause of death among cancer patients. Despite this, studies show that patients with cancer feel inadequately informed about the VTE risk and symptoms, which may impede their ability to recognise symptoms and react promptly. Patients with lung cancer are especially vulnerable due to a high relative risk of developing VTE combined with a high prevalence of low health literacy. This study aimed to explore the VTE information needs of lung cancer patients and how patients and healthcare professionals (HCPs) communicate about VTE.

Material and methods

Data was collected via semi-structured interviews with patients with lung cancer and HCPs. All participants (n = 20) were recruited from an oncological department. The analysis was performed in an inductive manner using a Ricoeur inspired strategy.

Findings

Patients had varying information needs regarding VTE, but HCPs did not routinely communicate about VTE, as the topic tended to be lowly prioritised. HCPs communicated about VTE when patients expressed a need or presented symptoms of VTE. HCPs expressed concerns about adding to patient's emotional burden by informing about VTE, while some patients emphasised the importance of being mentally prepared for potential complications.

Conclusion

The study demonstrates the challenging balance HCPs must maintain between adequately communicating about VTE and not causing undue psychological distress. However, given patient's often limited awareness of VTE, the responsibility to initiate communication about VTE must fall on the HCPs.

背景静脉血栓栓塞症(VTE)是导致癌症患者死亡的主要原因。尽管如此,研究表明癌症患者对 VTE 的风险和症状了解不足,这可能会影响他们识别症状和及时做出反应的能力。肺癌患者由于罹患 VTE 的相对风险较高,加之健康知识普及率较低,因此尤其容易受到 VTE 的影响。本研究旨在探讨肺癌患者对 VTE 信息的需求,以及患者和医疗保健专业人员(HCPs)如何就 VTE 进行沟通。所有参与者(n = 20)均来自肿瘤科。研究结果患者对 VTE 的信息需求各不相同,但医护人员并不经常就 VTE 进行交流,因为这一话题的优先级较低。当患者表示有需要或出现 VTE 症状时,医疗保健人员才会就 VTE 进行交流。HCPs 表示担心告知 VTE 会加重患者的精神负担,而一些患者则强调了为潜在并发症做好心理准备的重要性。然而,由于患者对 VTE 的认识往往有限,因此启动 VTE 沟通的责任必须由医疗保健人员承担。
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引用次数: 0
Corrigendum to “Inhibitory effects of resveratrol on platelet activation and thrombosis in colon cancer through regulation of the MAPK and cGMP/VASP pathways” [Thromb. Res. 2024 Aug 2:241:109111] 白藜芦醇通过调节 MAPK 和 cGMP/VASP 通路对结肠癌患者血小板活化和血栓形成的抑制作用》的更正 [Thromb.]
IF 3.7 3区 医学 Q1 HEMATOLOGY Pub Date : 2024-08-29 DOI: 10.1016/j.thromres.2024.109131
Ze Yu , Wenwen Zhu , Fengyan Lu , Hong Liu , Haitao Sun , Jinliang Dong , Yingjie Zhang , Hongqiang Wang
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引用次数: 0
Regulation of fibrinogen synthesis 纤维蛋白原合成的调节
IF 3.7 3区 医学 Q1 HEMATOLOGY Pub Date : 2024-08-28 DOI: 10.1016/j.thromres.2024.109134
Dre'Von A. Dobson , Richard J. Fish , Paul S. de Vries , Alanna C. Morrison , Marguerite Neerman-Arbez , Alisa S. Wolberg

The plasma protein fibrinogen is encoded by 3 structural genes (FGA, FGB, and FGG) that are transcribed to mRNA, spliced, and translated to 3 polypeptide chains (Aα, Bβ, and γ, respectively). These chains are targeted for secretion, decorated with post-translational modifications, and assembled into a hexameric “dimer of trimers” (AαBβγ)2. Fully assembled fibrinogen is secreted into the blood as a 340 kDa glycoprotein. Fibrinogen is one of the most prevalent coagulation proteins in blood, and its expression is induced by inflammatory cytokines, wherein circulating fibrinogen levels may increase up to 3-fold during acute inflammatory events. Abnormal levels of circulating fibrinogen are associated with bleeding and thrombotic disorders, as well as several inflammatory diseases. Notably, therapeutic strategies to modulate fibrinogen levels have shown promise in experimental models of disease. Herein, we review pathways mediating fibrinogen synthesis, from gene expression to secretion. Knowledge of these mechanisms may lead to the identification of biomarkers and new therapeutic targets to modulate fibrinogen in health and disease.

血浆蛋白纤维蛋白原由 3 个结构基因(FGA、FGB 和 FGG)编码,这些基因转录为 mRNA、剪接并翻译成 3 条多肽链(分别为 Aα、Bβ 和 γ)。这些多肽链以分泌为目标,经过翻译后修饰,组装成六聚体的 "三聚体的二聚体"(AαBβγ)2。完全组装后的纤维蛋白原以 340 kDa 糖蛋白的形式分泌到血液中。纤维蛋白原是血液中最常见的凝血蛋白之一,其表达受炎症细胞因子的诱导,在急性炎症事件中,循环中的纤维蛋白原水平可增加 3 倍。循环纤维蛋白原水平异常与出血和血栓性疾病以及多种炎症性疾病有关。值得注意的是,调节纤维蛋白原水平的治疗策略已在疾病的实验模型中显示出前景。在此,我们回顾了从基因表达到分泌的纤维蛋白原合成途径。对这些机制的了解可能有助于确定生物标志物和新的治疗靶点,以调节健康和疾病中的纤维蛋白原。
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引用次数: 0
The Attend-PE model: A feasibility study of a structured follow-up care model for patients with pulmonary embolism. Attend-PE模式:肺栓塞患者结构化随访护理模式的可行性研究。
IF 3.7 3区 医学 Q1 HEMATOLOGY Pub Date : 2024-08-24 DOI: 10.1016/j.thromres.2024.109133
Annesofie Løvdahl Hansen , Anette Arbjerg Højen , Stine Foged Lindegaard , Erik Lerkevang Grove , Christina Jakobsen , Nanna Rolving

Background

Pulmonary embolism may have both physical and psychological consequences for the affected person. Guidelines recommend structured follow-up care, yet this is still not widely practised. Therefore, a national research project was initiated in Denmark in 2021, with the aim of developing, testing, implementing, and evaluating a structured post-pulmonary embolism follow-up care model, ‘Attend-PE’. The objective of this feasibility study was to examine the fidelity, acceptability, and appropriateness of the Attend-PE model in a Danish hospital setting.

Methods

This feasibility study was conducted in two Danish hospitals, using a prospective study design with six months' follow-up. The fidelity, acceptability, and appropriateness of the Attend-PE model's components were evaluated using surveys, registrations sheets, and interviews with two physicians, three nurses, and 29 patients. Qualitative data were analysed using a deductive content analysis, while quantitative data were analysed using descriptive statistics.

Results

Fidelity with the Attend-PE model was good, with a high participation rate of patients in all components of the model. Acceptability was likewise good, as both patients and health care professionals expressed a high level of satisfaction with the model. The health care professionals considered the model to be relevant and suitable in a Danish hospital setting, confirming appropriateness of the model.

Conclusion

This study showed that the Attend-PE model for patients with pulmonary embolism is feasible and acceptable in a Danish hospital setting.

背景肺栓塞可能会对患者造成生理和心理上的双重影响。指南建议进行结构化的后续护理,但这一做法仍未得到广泛实施。因此,丹麦于 2021 年启动了一项国家研究项目,旨在开发、测试、实施和评估结构化肺栓塞后随访护理模式 "Attend-PE"。这项可行性研究的目的是在丹麦的医院环境中考察Attend-PE模式的忠实度、可接受性和适宜性。方法这项可行性研究在丹麦的两家医院进行,采用前瞻性研究设计,随访六个月。通过问卷调查、登记表以及与两名医生、三名护士和 29 名患者的访谈,对 Attend-PE 模式各组成部分的忠实性、可接受性和适宜性进行了评估。定性数据采用演绎内容分析法进行分析,定量数据则采用描述性统计法进行分析。结果Attend-PE 模式的忠实性良好,患者对该模式所有组成部分的参与率都很高。可接受性同样良好,患者和医护人员对该模式的满意度都很高。医护专业人员认为该模式与丹麦医院环境相关且适用,从而证实了该模式的适当性。 结论这项研究表明,针对肺栓塞患者的 Attend-PE 模式在丹麦医院环境中是可行且可接受的。
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引用次数: 0
Venous thromboembolism in the era of machine learning and artificial intelligence in medicine 机器学习和人工智能医学时代的静脉血栓栓塞症
IF 3.7 3区 医学 Q1 HEMATOLOGY Pub Date : 2024-08-23 DOI: 10.1016/j.thromres.2024.109121
Morayma Reyes Gil , Joshua Pantanowitz , Hooman H. Rashidi

In this review, we embark on a comprehensive exploration of venous thromboembolism (VTE) in the context of medical history and its current practice within medicine. We delve into the landscape of artificial intelligence (AI), exploring its present utility and envisioning its transformative roles within VTE management, from prevention to screening and beyond. Central to our discourse is a forward-looking perspective on the integration of AI within VTE in medicine, advocating for rigorous study design, robust validation processes, and meticulous statistical analysis to gauge the efficacy of AI applications. We further illuminate the potential of large language models and generative AI in revolutionizing VTE care, while acknowledging their inherent limitations and proposing innovative solutions to overcome challenges related to data availability and integrity, including the strategic use of synthetic data. The critical importance of navigating ethical, legal, and privacy concerns associated with AI is underscored, alongside the imperative for comprehensive governance and policy frameworks to regulate its deployment in VTE treatment. We conclude on a note of cautious optimism, where we highlight the significance of proactively addressing the myriad challenges that accompany the advent of AI in healthcare. Through diligent design, stringent validation, extensive education, and prudent regulation, we can harness AI's potential to significantly enhance our understanding and management of VTE. As we stand on the cusp of a new era, our commitment to these principles will be instrumental in ensuring that the promise of AI is fully realized within the realm of VTE care.

在这篇综述中,我们将结合医学史和当前的医学实践,对静脉血栓栓塞症(VTE)进行全面探讨。我们深入探讨了人工智能(AI)的发展前景,探讨了其目前的实用性,并展望了其在 VTE 管理(从预防到筛查及其他)中的变革性作用。我们论述的核心是以前瞻性的视角来看待人工智能与 VTE 在医学中的整合,主张采用严格的研究设计、稳健的验证流程和细致的统计分析来衡量人工智能应用的有效性。我们进一步阐明了大型语言模型和生成式人工智能在彻底改变 VTE 护理方面的潜力,同时承认其固有的局限性,并提出了创新的解决方案,以克服与数据可用性和完整性相关的挑战,包括合成数据的战略性使用。我们强调了驾驭与人工智能相关的伦理、法律和隐私问题的极端重要性,以及建立全面的治理和政策框架以规范其在 VTE 治疗中的应用的必要性。最后,我们持谨慎乐观的态度,强调了积极应对人工智能在医疗保健领域出现的各种挑战的重要性。通过勤奋的设计、严格的验证、广泛的教育和审慎的监管,我们可以利用人工智能的潜力来大大提高我们对 VTE 的理解和管理。当我们站在新时代的风口浪尖时,我们对这些原则的承诺将有助于确保人工智能的承诺在 VTE 护理领域得到充分实现。
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引用次数: 0
Development and testing of a mobile app for systematic collection of patient-reported outcomes (PROs) in patients with hemophilia 开发和测试用于系统收集血友病患者患者报告结果 (PROs) 的移动应用程序
IF 3.7 3区 医学 Q1 HEMATOLOGY Pub Date : 2024-08-22 DOI: 10.1016/j.thromres.2024.109122
J.E. Megías-Vericat , S. Bonanad Boix , S. Haya Guaita , M. Aguilar Rodríguez , E. Viciano Delibano , E. Monte-Boquet , A.R. Cid Haro , S. Pérez-Alenda , T. Palanques-Pastor , P. Bosch , B. Saubí-Cañete , C. Pérez-Rambla , F.J. Pérez-Sádaba , J.L. Poveda Andrés
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引用次数: 0
Efficacy and safety of intra-operative thromboprophylaxis with low-molecular-weight-heparin or heparin in patients undergoing surgical resection of colorectal cancer: A post-hoc analysis of the PERIOP-01 trial 接受结直肠癌手术切除的患者术中使用低分子量肝素或肝素进行血栓预防的有效性和安全性:PERIOP-01 试验的事后分析
IF 3.7 3区 医学 Q1 HEMATOLOGY Pub Date : 2024-08-20 DOI: 10.1016/j.thromres.2024.109123
Tzu-Fei Wang , Ranjeeta Mallick , Abdelrahman Noureldin , Amanda Pecarskie , Marc Carrier , Rebecca Auer , PERIOP-01 investigators
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引用次数: 0
A comparative study on the haemostatic changes in kidney failure patients: Pre- and post- haemodialysis and haemodiafiltration 肾衰竭患者止血变化的比较研究:血液透析和血液滤过前后
IF 3.7 3区 医学 Q1 HEMATOLOGY Pub Date : 2024-08-19 DOI: 10.1016/j.thromres.2024.109120
Caruana Jessica , Vella Kevin , Vella Amy Marie , Borg Marica , Cini Masini Maria , Farrugia Emanuel , Camilleri Liberato , Riva Nicoletta , Gatt Alexander

Background

Individuals with kidney failure have a compromised haemostatic system making them susceptible to both thrombosis and bleeding.

Objectives

Assessment of primary haemostasis in patients treated with either haemodialysis (HD) or haemodiafiltration (HDF) was performed through the measurement of several coagulation-based tests, both pre- and post-dialysis.

Patients/methods

41 renal failure patients and 40 controls were recruited. Platelet aggregometry, Factor XIII (FXIII), Fibrinogen, Von Willebrand Factor (VWF) and Soluble P-Selectin (sP-Sel) levels were measured.

Results

Maximum platelet aggregation was diminished in renal patients irrespective of aspirin intake. Post-dialysis, platelet function was exacerbated. Pre-dialysis FXIII levels were similar to the healthy cohort and became elevated post-dialysis. This elevation could not be explained by the relative decrease of water by dialysis. Fibrinogen levels were already elevated pre-dialysis and further increased post-dialysis. This elevation was associated with the relative decrease of water by dialysis. VWF levels in males were similar to the healthy cohort and became elevated post-dialysis. This elevation was associated with dialysis-related water loss. VWF antigen and activity in female patients were already elevated pre-dialysis and further increased post-dialysis with the exception of VWF activity in HDF treated female patients. sP-Sel levels were lower than those of the healthy cohort and became similar to the healthy cohort post-dialysis. This elevation could not be explained by the relative decrease of water by dialysis.

Conclusions

Whilst platelet aggregometry was diminished, we noted elevated clotting factors such as fibrinogen, FXIII and VWF with no significant differences between HD and HDF-treated patients.

背景肾衰竭患者的止血系统受到损害,因此很容易发生血栓和出血。目的通过测量透析前和透析后的几项凝血测试,评估接受血液透析(HD)或血液透析滤过(HDF)治疗的患者的原发性止血情况。对血小板聚集率、因子 XIII (FXIII)、纤维蛋白原、冯-威廉因子 (VWF) 和可溶性 P-选择素 (sP-Sel) 水平进行了测量。透析后,血小板功能加剧。透析前的 FXIII 水平与健康人群相似,透析后则升高。透析后水分相对减少无法解释这种升高。透析前纤维蛋白原水平已经升高,透析后进一步升高。这种升高与透析使水分相对减少有关。男性的 VWF 水平与健康人群相似,但在透析后升高。这种升高与透析导致的失水有关。女性患者的 VWF 抗原和活性在透析前已经升高,透析后进一步升高,但接受 HDF 治疗的女性患者的 VWF 活性除外。结论虽然血小板聚集率降低,但我们注意到纤维蛋白原、FXIII 和 VWF 等凝血因子升高,HD 和 HDF 治疗患者之间无显著差异。
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引用次数: 0
The association between pembrolizumab and risk of venous thromboembolism in patients with breast cancer 彭博利珠单抗与乳腺癌患者静脉血栓栓塞风险之间的关系
IF 3.7 3区 医学 Q1 HEMATOLOGY Pub Date : 2024-08-17 DOI: 10.1016/j.thromres.2024.109119
Cho-Han Chiang , Xiaocao Xu , Junmin Song , Nutchapon Xanthavanij , Kuan-Yu Chi , Yu-Cheng Chang , Yu Chang , Chieh-Lien Hsiao , Cho-Hung Chiang , Shuwen Lin
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引用次数: 0
期刊
Thrombosis research
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