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New drugs, old problems: immune checkpoint inhibitors and cancer-associated thrombosis 新药物,老问题:免疫检查点抑制剂与癌症相关性血栓形成
Pub Date : 2024-05-16 DOI: 10.4081/btvb.2024.113
Mehrie H. Patel, Alok A. Khorana
A frequent side effect of cancer treatment is venous thromboembolism (VTE), which is made more likely by systemic anticancer medication. Immune checkpoint inhibitors (ICIs) have emerged as a paradigm-shifting treatment for many cancers. Early trials investigating the efficacy of ICIs did not identify thrombosis as a significant adverse event of concern. An initial meta-analysis reported a 1.1% [95% confidence interval (CI) 0.5-2.1] risk of arterial thromboembolism (ATE) and a 2.7% (95% CI 1.8-4.0) rate of vein thrombosis. ICIs have, however, been linked to ATE and VTE in an increasing number of post-marketing investigations. The reported incidence rates of cumulative VTE range from 5-8% at 6 months to 10-12% at 12 months, while the rates of ATE vary from 1-2% at 6 months to 17 months. Furthermore, a number of studies show a correlation between reduced survival and ICI-related thromboembolism. In order to provide a compiled and thorough narrative on the mechanisms, incidence, risk factors, and survival related to ICI-associated VTE and ATE, this narrative review summarizes the literature.
癌症治疗的一个常见副作用是静脉血栓栓塞症(VTE),而全身性抗癌药物更容易导致这种副作用。免疫检查点抑制剂(ICIs)的出现改变了许多癌症的治疗模式。早期研究 ICIs 疗效的试验并未发现血栓形成是一个值得关注的重大不良事件。最初的一项荟萃分析报告显示,动脉血栓栓塞(ATE)风险为 1.1% [95% 置信区间 (CI) 0.5-2.1],静脉血栓形成率为 2.7% (95% CI 1.8-4.0)。然而,在越来越多的上市后调查中,ICIs 已与 ATE 和 VTE 联系在一起。报告的累积 VTE 发生率从 6 个月时的 5%-8%到 12 个月时的 10%-12%不等,而 ATE 发生率则从 6 个月时的 1%-2%到 17 个月时的 1%-2%不等。此外,许多研究表明,生存率降低与 ICI 相关血栓栓塞之间存在相关性。为了对 ICI 相关 VTE 和 ATE 的机制、发病率、风险因素和存活率进行汇编和详尽阐述,本综述对相关文献进行了总结。
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引用次数: 0
Endothelial cell dysfunction in cancer: a not-so-innocent bystander 癌症中的内皮细胞功能障碍:不那么无辜的旁观者
Pub Date : 2024-05-16 DOI: 10.4081/btvb.2024.116
Betül Ünlü, Neha Joshi, Jamie M. O'Sullivan
The body’s homeostasis depends on the vascular endothelium, which controls angiogenesis, vascular tone, inflammation, cell trafficking, hemostasis, and the movement of nutrients and waste out of the body. Endothelial cells (ECs) are the primary gatekeepers of many of these vessel wall functions, despite only having a single cell’s thickness. Normally quiescent ECs in the context of cancer are activated by anti-cancer therapies, the tumor microenvironment, and factors secreted by the tumor. Crucially, this dysfunctional endothelium actively participates in tumor metastasis and progression rather than just acting as a passive bystander. Compared to the healthy vasculature, ECs in the tumor vasculature are heterogeneous and have a different gene expression profile. Tumor-associated ECs, in particular, exhibit increased pro-angiogenic characteristics and upregulated expression of adhesion molecules and proinflammatory cytokines, facilitating the intra- and extravasation of spreading tumor cells. Furthermore, the downregulation of important anticoagulant molecules and increased endothelial secretion of prothrombotic molecules can directly encourage cancer-associated thrombosis. Many anti-cancer therapies are also less effective in their delivery and function when there is dysfunction in the tumor endothelium. The review highlights some of the most recent research showing how tumor-associated ECs influence angiogenesis, inflammation, coagulation, and metastasis to contribute to the progression of tumors. Undoubtedly, a better understanding of how the tumor microenvironment subverts quiescent ECs and how phenotypic alterations in the vessel wall support the survival and spread of tumor cells will aid in the identification of new therapeutic targets to slow the advancement of cancer.
人体的平衡依赖于血管内皮,它控制着血管生成、血管张力、炎症、细胞贩运、止血以及营养物质和废物的排出。尽管血管内皮细胞(EC)只有一个细胞的厚度,但它却是许多血管壁功能的主要看门人。在癌症情况下,通常处于静止状态的内皮细胞会被抗癌疗法、肿瘤微环境和肿瘤分泌的因子激活。重要的是,这种功能失调的内皮会积极参与肿瘤的转移和进展,而不仅仅是被动的旁观者。与健康血管相比,肿瘤血管中的内皮细胞具有异质性,基因表达谱也不同。尤其是肿瘤相关的 ECs,其促血管生成特性增强,粘附分子和促炎症细胞因子的表达上调,从而促进了扩散的肿瘤细胞在体内和体外的浸润。此外,重要抗凝分子的下调和内皮促血栓形成分子分泌的增加会直接促进癌症相关血栓的形成。当肿瘤内皮功能失调时,许多抗癌疗法的效果和作用也会大打折扣。本综述重点介绍了一些最新研究,这些研究显示了肿瘤相关内皮细胞如何影响血管生成、炎症、凝血和转移,从而导致肿瘤进展。毫无疑问,更好地了解肿瘤微环境如何颠覆静止的EC,以及血管壁的表型改变如何支持肿瘤细胞的生存和扩散,将有助于确定新的治疗靶点,减缓癌症的进展。
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引用次数: 0
Venous thromboembolism and mortality in patients with hematological malignancies 血液恶性肿瘤患者的静脉血栓栓塞与死亡率
Pub Date : 2024-05-16 DOI: 10.4081/btvb.2024.119
Kristen M. Sanfilippo, Tzu-Fei Wang
Mortality and venous thromboembolism (VTE) are major risks for patients with hematological malignancies. However, they are commonly underrepresented in major clinical trials of VTE. Treatment decisions are further complicated by the unique characteristics they frequently exhibit, such as thrombocytopenia. In addition to discussing treatment challenges, knowledge gaps, and future directions, our goal in this narrative review is to provide an overview of the epidemiology and risk factors of mortality in patients with hematological malignancies and VTE.
死亡率和静脉血栓栓塞(VTE)是血液恶性肿瘤患者面临的主要风险。然而,在有关 VTE 的主要临床试验中,血液恶性肿瘤患者的比例通常偏低。由于他们经常表现出血小板减少等独特特征,治疗决策变得更加复杂。除了讨论治疗挑战、知识差距和未来方向外,我们在这篇叙述性综述中的目标是概述血液恶性肿瘤和 VTE 患者的流行病学和死亡风险因素。
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引用次数: 0
Location of metastasis and complications in patients with venous thromboembolism and cancer: systematic review 静脉血栓栓塞症和癌症患者的转移位置与并发症:系统性综述
Pub Date : 2024-05-16 DOI: 10.4081/btvb.2024.114
M. Barca-Hernando, Victor Garcia-Garcia, L. Jara-Palomares
According to current guidelines, patients with venous thromboembolism (VTE) and active cancer should receive prolonged anticoagulant treatment (>6 months). In patients with cancer-associated thrombosis (CAT), metastasis is a factor in recurrent VTE and bleeding; however, the function of metastasis location remains unclear. In order to assess the risk of complications (such as bleeding or recurrent VTE) based on the location of metastases in patients with CAT, we conducted a systematic review. The PubMed database search was used to perform a systematic review. MESH terms pertaining to metastasis, VTE, and neoplasms were employed. Patients with CAT who were at least eighteen years old and receiving therapeutic doses of anticoagulants were included, as were details regarding the locations of metastases and the availability of patients who had complications (bleeding or recurrent VTE). Among the 1,447 articles found by the search, 7 retrospective studies met all eligibility requirements and were added to the analysis. The majority of these studies addressed brain metastases. Studies found that intracranial hemorrhage occurred between 4% and 19% of the time. In the context of brain metastases and VTE, other studies examined the safety and effectiveness of direct oral anticoagulants in comparison to low-molecular-weight heparin. This systematic review draws attention to the paucity of data regarding the impact of metastasis location on complications in CAT patients. Further research is required to assess the effect of metastasis location on the risk of VTE complications in patients with CAT.
根据现行指南,静脉血栓栓塞症(VTE)和活动性癌症患者应接受长期抗凝治疗(>6 个月)。在癌症相关血栓形成(CAT)患者中,转移是导致复发性 VTE 和出血的一个因素;然而,转移位置的作用仍不明确。为了根据 CAT 患者转移瘤的位置评估并发症(如出血或复发性 VTE)的风险,我们进行了一项系统性综述。我们使用 PubMed 数据库进行了系统性回顾。采用了与转移、VTE 和肿瘤有关的 MESH 术语。研究对象包括年满 18 周岁且正在接受治疗剂量抗凝药物的 CAT 患者,以及转移灶位置和出现并发症(出血或复发性 VTE)患者的详细情况。在搜索到的 1,447 篇文章中,有 7 项回顾性研究符合所有资格要求并被纳入分析。这些研究大多涉及脑转移。研究发现,颅内出血的发生率在 4% 到 19% 之间。针对脑转移和 VTE,其他研究考察了直接口服抗凝剂与低分子量肝素相比的安全性和有效性。本系统综述提醒人们注意有关转移瘤位置对 CAT 患者并发症影响的数据很少。需要进一步研究评估转移瘤位置对CAT患者VTE并发症风险的影响。
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引用次数: 0
Trends and updates on the epidemiology of cancer-associated thrombosis: a systematic review 癌症相关血栓流行病学的趋势和最新情况:系统综述
Pub Date : 2024-05-16 DOI: 10.4081/btvb.2024.108
Ang Li, Emily Zhou
For cancer patients, cancer-associated thrombosis (CAT) is a serious complication. An updated epidemiology of CAT over the last ten years is summarized in this review. A comprehensive analysis of pertinent population cohort research released between 2011 and 2024 was carried out. In patients with unselected cancers, the 12-month incidence of CAT is roughly 3-5% (9-fold increase vs to the matched non-cancer population); however, in patients with advanced cancers requiring systemic therapy, the risk rises to 6-8% (20-fold increase vs. to the matched non-cancer population). Anticoagulation use and adherence have improved, but the risk of recurrence is still high, at 5-8% at 6 months and 7-15% at 12 months. The type, stage, and treatment of cancer, a history of venous thromboembolism (VTE), prolonged hospitalization or immobilization, and obesity are significant clinical predictors of the development of CAT. The modified Vienna-CATS and EHR-CAT have the best performance (area under the curve 0.68-0.71) among the clinical risk prediction scores for CAT using the original Khorana score backbone that has been externally validated. However, additional research is required to guarantee appropriate implementation and utilization of these models. Even with contemporary antineoplastic treatments, CAT is still a major complication for cancer patients. We encourage interdisciplinary partnerships among hematologists, data scientists, epidemiologists, and oncologists to guarantee the integration of customized VTE risk evaluation into standard oncologic treatment.
对于癌症患者来说,癌症相关血栓形成(CAT)是一种严重的并发症。本综述总结了过去十年中 CAT 的最新流行病学情况。我们对 2011 年至 2024 年间发布的相关人群队列研究进行了全面分析。在未经选择的癌症患者中,CAT 的 12 个月发病率约为 3-5%(与匹配的非癌症人群相比增加了 9 倍);然而,在需要系统治疗的晚期癌症患者中,风险上升到 6-8%(与匹配的非癌症人群相比增加了 20 倍)。抗凝治疗的使用和依从性有所改善,但复发风险仍然很高,6 个月时为 5-8%,12 个月时为 7-15%。癌症的类型、分期和治疗方法、静脉血栓栓塞症(VTE)病史、长期住院或固定不动以及肥胖都是诱发 CAT 的重要临床预测因素。修改后的维也纳-CATS 和 EHR-CAT 在使用经外部验证的原始 Khorana 评分骨干的 CAT 临床风险预测评分中表现最佳(曲线下面积为 0.68-0.71)。然而,要保证这些模型的适当实施和使用,还需要进行更多的研究。即使采用了现代抗肿瘤治疗方法,CAT 仍是癌症患者的主要并发症。我们鼓励血液科医生、数据科学家、流行病学家和肿瘤学家之间的跨学科合作,以确保将定制的 VTE 风险评估纳入标准的肿瘤治疗中。
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引用次数: 0
Diagnosis and management of abnormal uterine bleeding in adolescence 青春期异常子宫出血的诊断和处理
Pub Date : 2024-05-08 DOI: 10.4081/btvb.2024.106
Roberto Mario Santi, Annamaria Fulghesu, Ezio Zanon, E. De Candia, Elvira Grandone, Giancarlo Di Renzo, Claudia Succu, V. Tosto, Vincenzina Bruni, Paolo Gresele
During menarche and adolescence, abnormal uterine bleeding (AUB) may serve as a crucial indicator of a hidden bleeding disorder. When a young woman is suspected of having a bleeding disorder, the obstetrician-gynecologist should collaborate with a hemostasis specialist to arrange the necessary laboratory testing and determine the best course of action. The Italian Society for the Study of Hemostasis and Thrombosis and the Italian Society of Gynecology and Obstetrics jointly offer recommendations on the diagnosis and treatment of AUB. They also suggest diagnostic and therapeutic pathways to decrease diagnostic delay and improve treatment effectiveness and safety.
在月经初潮期和青春期,异常子宫出血(AUB)可能是隐性出血性疾病的一个重要指标。当年轻女性被怀疑患有出血性疾病时,妇产科医生应与止血专家合作,安排必要的实验室检查并确定最佳治疗方案。意大利止血与血栓研究学会和意大利妇产科学会联合提出了 AUB 诊断和治疗建议。它们还提出了诊断和治疗路径,以减少诊断延误,提高治疗效果和安全性。
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引用次数: 0
Tailored therapy with turoctocog alfa pegol according to patient’s lifestyle and hemorrhagic phenotype: from clinical trial to real-life 根据患者的生活方式和出血表型量身定制的 turoctocog alfa pegol 疗法:从临床试验到现实生活
Pub Date : 2024-04-22 DOI: 10.4081/btvb.2024.104
Ilaria Nichele, Giuseppe Carli, A. Tosetto
Although the use of prophylaxis regimens with prolonged half-life factors is now widespread in the world of hemophilia A, there is a lack of real-life evidence on the impact of these products on joint health, adherence, and quality of life of patients. Turoctocog alfa pegol is a glycoPEGylated recombinant factor VIII (FVIII) with an extended half-life (EHL), developed for prophylaxis, treatment of bleeds, and perioperative management in patients with hemophilia A. We report here on three cases of three patients affected by severe hemophilia A, with variable bleeding phenotype and lifestyle, to describe our clinical practice on prophylaxis with turoctocog alfa pegol. As confirmed in our cases, FVIII trough levels remained coherent with those experienced in the registration trial after the switch to the commercial EHL drug. Moreover, the cases highlight how the current clinical management of hemophilia can personalize treatment in several specific conditions.
尽管使用延长半衰期因子的预防方案目前在 A 型血友病领域已得到广泛应用,但缺乏有关这些产品对患者关节健康、依从性和生活质量的影响的实际证据。Turoctocog alfa pegol 是一种半衰期(EHL)较长的糖蛋白化重组因子 VIII (FVIII),开发用于 A 型血友病患者的预防、出血治疗和围手术期管理。我们在此报告了三例严重 A 型血友病患者的病例,他们的出血表型和生活方式各不相同,并介绍了我们使用 Turoctocog alfa pegol 进行预防的临床实践。我们的病例证实,在改用商用 EHL 药物后,FVIII 谷值水平与注册试验中的水平保持一致。此外,这些病例还突显了当前的血友病临床治疗如何在几种特殊情况下实现个性化治疗。
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引用次数: 0
ReDIP, the Italian network for the diagnosis of congenital platelet function disorders ReDIP,意大利先天性血小板功能障碍诊断网络
Pub Date : 2024-04-22 DOI: 10.4081/btvb.2024.134
Marco Cattaneo, Claudia Ghali, M. Scavone
Congenital platelet function disorders (cPFD) are associated with an increased risk of mucocutaneous bleeding of various levels of severity; they may be classified based on abnormalities of platelet components that share common characteristics: i) platelet receptors for adhesive proteins; ii) platelet receptors for soluble agonists; iii) platelet granules; iv) signal transduction pathways; v) procoagulant phospholipids; less well characterized PFD aregrouped in a sixth category of miscellaneous abnormalities [...].
先天性血小板功能障碍(cPFD)与不同严重程度的皮肤粘膜出血风险增加有关;可根据具有共同特征的血小板成分异常进行分类:i) 黏附蛋白的血小板受体;ii) 可溶性激动剂的血小板受体;iii) 血小板颗粒;iv) 信号转导途径;v) 促凝血磷脂;特征不明显的先天性血小板功能障碍被归入第六类杂项异常[...]。
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引用次数: 0
Palestinian patient associations appeal on World Hemophilia Day 巴勒斯坦患者协会在世界血友病日发出呼吁
Pub Date : 2024-04-17 DOI: 10.4081/btvb.2024.136
Sara Mellano
Ensuring access to life-saving therapies for Palestinian hemophilia patients and safeguarding their right to health, along with committing to long-term goals such as establishing a Palestinian Hemophilia Federation and systematically implementing updated and internationally recognized treatment protocols, is the appeal directed to the international community by Palestinian sector associations [...].
确保巴勒斯坦血友病患者获得拯救生命的疗法,保障他们的健康权,同时致力于实现长期目标,如建立巴勒斯坦血友病联合会,系统地实施最新的国际公认的治疗方案,这是巴勒斯坦各部门协会向国际社会发出的呼吁[......]。
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引用次数: 0
The diagnostic procedure for subjects with suspected pulmonary embolism. A recent comparison among the recommendations available from the international guidelines 疑似肺栓塞患者的诊断程序。国际指南建议的最新比较
Pub Date : 2024-03-19 DOI: 10.4081/btvb.2024.122
G. Palareti
Acute pulmonary embolism (PE) is a common and potentially life-threatening disease characterized by the occlusion of arterial lung vasculature, typically due to thrombi traveling from a thrombotic vein in the lower limb. Several guidelines have been proposed worldwide to assist clinicians in its diagnosis, however, they are not consistent on the usage of diagnostic tools. This commentary reviews the literature and discusses the concordance/discordance between these international guidelines on PE diagnosis.
急性肺栓塞(PE)是一种常见的、可能危及生命的疾病,其特点是肺部动脉血管闭塞,通常是由于血栓从下肢的血栓静脉流出所致。世界范围内已经提出了一些指南来帮助临床医生进行诊断,但在诊断工具的使用上并不一致。本评论回顾了相关文献,并讨论了这些国际指南在 PE 诊断方面的一致性/不一致性。
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引用次数: 0
期刊
Bleeding, Thrombosis and Vascular Biology
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