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A Systematic Review of Efficacy and Safety of Plasma-Derived von Willebrand Factor/Factor VIII Concentrate (Voncento) in von Willebrand Disease. 血浆衍生冯-维勒布兰德因子/因子 VIII 浓缩液 (Voncento®) 治疗冯-维勒布兰德病的有效性和安全性系统回顾。
IF 5 2区 医学 Q1 HEMATOLOGY Pub Date : 2024-09-01 Epub Date: 2024-01-25 DOI: 10.1055/a-2253-9701
Lucia Rugeri, Will Thomas, Kathrin Schirner, Lisa Heyder, Günter Auerswald

Background:  For the treatment of von Willebrand disease (VWD), von Willebrand factor (VWF) concentrates can be used in on-demand, long-term prophylaxis, and surgical prophylaxis regimens.

Methods:  This systematic literature review was conducted to evaluate the efficacy, consumption, and safety of plasma-derived human coagulation FVIII/human VWF (pdVWF/FVIII; Voncento/Biostate) for the treatment of patients with any inherited VWD type. An electronic search was conducted in MEDLINE and Cochrane Library databases on VWD therapies. All retrieved publications were assessed against predefined inclusion/exclusion criteria following the Cochrane group recommendations. Associated pharmacovigilance data were collected across the same time period.

Results:  Eleven publications from eight study cohorts were identified for data retrieval. All were from multicenter studies and included both pediatric and adult patients. Eight publications included evaluations of the efficacy of pdVWF/FVIII for on-demand treatment, eight included long-term prophylactic treatment, and eight included surgical prophylaxis. Treatment protocols and VWF administration methods differed between studies, as did safety evaluations. The clinical response was rated as excellent/good for on-demand treatment in 66 to 100% of nonsurgical bleeds, 89 to 100% in the treatment of breakthrough bleeds during long-term prophylaxis treatment, and hemostatic efficacy in surgical procedures was 75 to 100%. Pharmacovigilance data confirmed a low incidence of adverse events in treated patients.

Conclusion:  This review provides a comprehensive summary of studies that evaluated the use of pdVWF/FVIII in VWD demonstrating the long-term effectiveness and safety of this pdVWF/FVIII across all ages, types of VWD, and treatment settings.

背景:为治疗冯-威廉氏病(VWD),冯-威廉因子(VWF)浓缩物可用于按需治疗、长期预防和手术预防方案:本系统性文献综述旨在评估血浆衍生人凝血 FVIII/人 VWF(pdVWF/FVIII;Voncento®/Biostate®)治疗任何遗传性 VWD 患者的疗效、用量和安全性。在 MEDLINE® 和 Cochrane Library 数据库中对 VWD 疗法进行了电子检索。根据 Cochrane 小组的建议,按照预定义的纳入/排除标准对所有检索到的出版物进行了评估。同时还收集了同期的相关药物警戒数据:数据检索确定了来自 8 个研究队列的 11 篇出版物。所有研究均来自多中心研究,包括儿童和成人患者。其中 8 篇论文评估了 pdVWF/FVIII 按需治疗的疗效,8 篇论文评估了长期预防性治疗的疗效,8 篇论文评估了手术预防性治疗的疗效。不同研究的治疗方案和 VWF 给药方法各不相同,安全性评估也不尽相同。在按需治疗中,67%-100%的非手术出血临床反应被评为优/良,在长期预防治疗中,88.9%-100%的突破性出血临床反应被评为优/良,外科手术中的止血效果为75%-100%。药物警戒数据证实,接受治疗的患者不良反应发生率较低:本综述对评估 pdVWF/FVIII 在 VWD 中应用的研究进行了全面总结,证明了这种 pdVWF/FVIII 在所有年龄段、VWD 类型和治疗环境中的长期有效性和安全性。
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引用次数: 0
In-Hospital Pulmonary Arterial Embolism after Catheter Ablation of Over 45,000 Cardiac Arrhythmias: Individualized Case Analysis of Multicentric Data. 超过 45,000 例心律失常导管消融术后的院内肺动脉栓塞:多中心数据的个性化病例分析。
IF 5 2区 医学 Q1 HEMATOLOGY Pub Date : 2024-09-01 Epub Date: 2024-03-31 DOI: 10.1055/s-0044-1785519
Florian Doldi, Nele Geßler, Omar Anwar, Ann-Kathrin Kahle, Katharina Scherschel, Benjamin Rath, Julia Köbe, Philipp Sebastian Lange, Gerrit Frommeyer, Andreas Metzner, Christian Meyer, Stephan Willems, Karl-Heinz Kuck, Lars Eckardt

Objective and background:  Data on incidence of in-hospital pulmonary embolisms (PE) after catheter ablation (CA) are scarce. To gain further insights, we sought to provide new findings through case-based analyses of administrative data.

Methods:  Incidences of PE after CA of supraventricular tachycardias (SVT), atrial fibrillation (AF), atrial flutter (AFlu), and ventricular tachycardias (VT) in three German tertiary centers between 2005 and 2020 were determined and coded by the G-DRG (German Diagnosis Related Groups System) and OPS (German Operation and Procedure Classification) systems. An administrative search was performed with a consecutive case-based analysis.

Results:  Overall, 47,344 ablations were analyzed (10,037 SVT; 28,048 AF; 6,252 AFlu; 3,007 VT). PE occurred in 14 (0.03%) predominantly female (n = 9; 64.3%) patients with a mean age of 55.3 ± 16.9 years, body mass index 26.2 ± 5.1 kg/m2, and left ventricular ejection fraction of 56 ± 13.6%. PE incidences were 0.05% (n = 5) for SVT, 0.02% (n = 5) for AF, and 0.13% (n = 4) for VT ablations. No patient suffered PE after AFlu ablation. Five patients (35.7%) with PE after CA had no prior indication for oral anticoagulation (OAC). Preprocedural international normalized ratio in PE patients was 1.2 ± 0.5. Most patients with PE following CA presented with symptoms the day after the procedure (n = 9) after intraprocedural heparin application of 12,943.2 ± 5,415.5 IU. PE treatment included anticoagulation with either phenprocoumon (n = 5) or non-vitamin K-dependent OAC (n = 9). Two patients with PE died after VT/AF ablation, respectively. The remaining patients were discharged without sequels.

Conclusion:  Over a 15-year period, incidence of PE after ablation is low, particularly low in patients with ablation for AF/AFlu. This is most likely due to stricter anticoagulation management in these patients compared with those receiving SVT/VT ablation procedures and could argue for continuation of OAC prior to ablation. Optimizing periprocedural anticoagulation management should be subject of further prospective trials.

目的和背景:有关导管消融术(CA)后院内肺栓塞(PE)发生率的数据很少。为了进一步了解情况,我们试图通过对行政数据进行病例分析来提供新的发现:方法:通过G-DRG(德国诊断相关分组系统)和OPS(德国操作和程序分类)系统对2005年至2020年期间在德国三个三级中心发生的室上性心动过速(SVT)、心房颤动(AF)、心房扑动(AFlu)和室性心动过速(VT)导管消融术后PE的发生率进行了测定和编码。通过基于病例的连续分析进行了行政检索:共分析了 47344 例消融手术(10037 例 SVT;28048 例 AF;6252 例 AFlu;3007 例 VT)。14例(0.03%)发生 PE,主要为女性患者(n = 9;64.3%),平均年龄为 55.3 ± 16.9 岁,体重指数为 26.2 ± 5.1 kg/m2,左心室射血分数为 56 ± 13.6%。SVT PE发生率为0.05%(n = 5),房颤为0.02%(n = 5),VT消融为0.13%(n = 4)。没有患者在房颤消融术后发生 PE。5名(35.7%)在CA术后发生PE的患者之前没有口服抗凝药(OAC)的适应症。PE患者术前的国际标准化比值为(1.2 ± 0.5)。大多数 CA 后 PE 患者在术中应用肝素 12,943.2 ± 5,415.5 IU 后,于术后第二天出现症状(n = 9)。PE 治疗包括苯丙酮(5 例)或非维生素 K 依赖性 OAC(9 例)抗凝。两名 PE 患者分别在 VT/AF 消融术后死亡。结论:15年来,消融术后 PE 的发生率很低,尤其是因房颤/心房颤动而进行消融术的患者。这很可能是因为与接受 SVT/VT 消融术的患者相比,这些患者的抗凝管理更为严格,因此消融术前应继续使用 OAC。优化围术期抗凝管理应成为进一步前瞻性试验的主题。
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引用次数: 0
Marginal Zone B Cells Represent a Conserved Initiating Player in the Immune Response to Factor VIII in Hemophilia A Mice. 边缘区 B 细胞是 A 型血友病小鼠对因子 VIII 的免疫反应中的一个保守启动因子。
IF 5 2区 医学 Q1 HEMATOLOGY Pub Date : 2024-09-01 Epub Date: 2024-07-16 DOI: 10.1055/s-0044-1788559
Maya Maarouf, Seema R Patel, Wallace Hunter Baldwin, Patricia E Zerra, Courtney Cox, Ernest T Parker, Sean R Stowell, Shannon L Meeks
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引用次数: 0
Pulmonary Thromboembolism after Catheter Ablation of Cardiac Arrhythmias. 心律失常导管消融术后的肺血栓栓塞症。
IF 5 2区 医学 Q1 HEMATOLOGY Pub Date : 2024-09-01 Epub Date: 2024-07-16 DOI: 10.1055/a-2366-7245
Nebojsa Mujovic, Tatjana S Potpara
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引用次数: 0
Racial Differences in Ischemic and Hemorrhagic Stroke: An Ecological Epidemiological Study. 缺血性和出血性中风的种族差异:生态流行病学研究。
IF 5 2区 医学 Q1 HEMATOLOGY Pub Date : 2024-09-01 Epub Date: 2024-02-29 DOI: 10.1055/a-2278-8769
Dong-Seon Kang, Pil-Sung Yang, Daehoon Kim, Eunsun Jang, Hee Tae Yu, Tae-Hoon Kim, Jung-Hoon Sung, Hui-Nam Pak, Moon-Hyoung Lee, Gregory Y H Lip, Boyoung Joung

Background:  This study aimed to evaluate racial differences in the incidence of stroke by conducting an ecological epidemiological study using UK Biobank and Korean nationwide data.

Methods:  This study used individual data from the Korean National Health Insurance Service-Health Screening and UK Biobank, which included participants who underwent health examinations between 2006 and 2010. We included 112,750 East Asians (50.7% men, mean age: 52.6 years) and 210,995 Caucasians (44.7% men, mean age: 55.0 years) who were not diagnosed with atrial fibrillation, cardiovascular diseases, chronic kidney disease, chronic obstructive pulmonary disease, or cancer. The primary outcome was defined as a composite of ischemic and hemorrhagic stroke.

Results:  East Asians tended to have a lower body mass index (23.7 vs. 26.4 kg/m2, p < 0.001) and a higher proportion of participants who did not engage in moderate-to-vigorous physical activity (49.6% vs. 10.7%, p < 0.001) than Caucasians. During the follow-up, East Asians had higher 5-year incidence rates (presented as per 1,000 person-years) for primary outcome (1.73 vs. 0.50; IR ratio [IRR]: 3.48, 95% confidence interval [CI]: 3.13-3.88), ischemic stroke (1.23 vs. 0.33; IRR: 3.70, 95% CI: 3.25-4.21), hemorrhagic stroke (0.56 vs. 0.18; IRR: 3.20, 95% CI: 2.67-3.84), and atrial fibrillation-related stroke (0.19 vs. 0.09; IRR: 2.04, 95% CI: 1.55-2.68).

Conclusion:  Based on this ecological epidemiological study, racial differences in stroke incidence were robust to a variety of statistical analyses, regardless of the subtype. This suggests the need for region-specific approaches to stroke prevention.

背景:本研究旨在通过使用英国生物数据库和韩国全国数据进行生态流行病学研究,评估中风发病率的种族差异:本研究旨在利用英国生物库和韩国全国范围的数据开展生态流行病学研究,评估中风发病率的种族差异:本研究使用了韩国国民健康保险服务-健康筛查和英国生物库的患者级数据,其中包括 2006 年至 2010 年期间接受健康检查的参与者。我们纳入了112750名东亚人(50.7%为男性,平均年龄52.6岁)和210995名白种人(44.7%为男性,平均年龄55.0岁),他们均未被诊断出患有心房颤动、心血管疾病、慢性肾病、慢性阻塞性肺病或癌症。主要结果定义为缺血性和出血性中风的综合结果:与白种人相比,东亚人的体重指数往往较低(23.7 kg/m2 vs. 26.4 kg/m2,P < 0.001),不参加中度到剧烈运动的比例较高(49.6% vs. 10.7%,P < 0.001)。在随访期间,东亚人在主要结果(1.73 对 0.50;发病率比 [IRR] 3.48,95% 置信区间 [CI] 3.13-3.88)、缺血性中风(1.73 对 0.50;发病率比 [IRR] 3.48,95% 置信区间 [CI] 3.13-3.88)方面的五年发病率(以每千人年计)高于白种人。88)、缺血性中风(1.23 vs. 0.33;IRR 3.70,95% CI 3.25-4.21)、出血性中风(0.56 vs. 0.18;IRR 3.20,95% CI 2.67-3.84)和心房颤动相关中风(0.19 vs. 0.09;IRR 2.04,95% CI 1.55-2.68):结论:根据这项生态流行病学研究,不论是哪种亚型,中风发病率的种族差异在各种统计分析中都是稳健的。结论:根据这项生态流行病学研究,不管是哪种亚型,中风发病率的种族差异在各种统计分析中都很明显。
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引用次数: 0
Anticoagulation in Patients with Isolated Distal Deep Vein Thrombosis: Bringing the Puzzle Together. 孤立性远端深静脉血栓患者的抗凝治疗:拼凑谜题。
IF 5 2区 医学 Q1 HEMATOLOGY Pub Date : 2024-09-01 Epub Date: 2024-01-19 DOI: 10.1055/a-2250-3298
Nicola Potere, Yugo Yamashita, Walter Ageno
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引用次数: 0
Sensitivity to Aortic Rupture in Hereditary Aortic Diseases. 遗传性主动脉疾病对主动脉破裂的敏感性
IF 5 2区 医学 Q1 HEMATOLOGY Pub Date : 2024-08-31 DOI: 10.1055/a-2378-9201
Vivian de Waard
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引用次数: 0
Volume Regulation and Nonosmotic Volume of Individual Human Platelets Quantified by High-Speed Scanning Ion Conductance Microscopy. 通过高速扫描离子传导显微镜量化单个人体血小板的体积调节和非渗透体积。
IF 5 2区 医学 Q1 HEMATOLOGY Pub Date : 2024-08-29 DOI: 10.1055/a-2378-9088
Konstantin Krutzke, Jan Seifert, Meinrad Gawaz, Johannes Rheinlaender, Tilman E Schäffer

Background:  Platelets are anucleate cells that play an important role in wound closure following vessel injury. Maintaining a constant platelet volume is critical for platelet function. For example, water-induced swelling can promote procoagulant activity and initiate thrombosis. However, techniques for measuring changes in platelet volume such as light transmittance or impedance techniques have inherent limitations as they only allow qualitative measurements or do not work on the single-cell level.

Methods:  Here, we introduce high-speed scanning ion conductance microscopy (HS-SICM) as a new platform for studying volume regulation mechanisms of individual platelets. We optimized HS-SICM to quantitatively image the morphology of adherent platelets as a function of time at scanning speeds up to 7 seconds per frame and with 0.1 fL precision.

Results:  We demonstrate that HS-SICM can quantitatively measure the rapid swelling of individual platelets after a hypotonic shock and the following regulatory volume decrease (RVD). We found that the RVD of thrombin-, ADP-, and collagen-activated platelets was significantly reduced compared with nonactivated platelets. Applying the Boyle-van't Hoff relationship allowed us to extract the nonosmotic volume and volume fraction on a single-platelet level. Activation by thrombin or ADP, but not by collagen, resulted in a decrease of the nonosmotic volume, likely due to a release reaction, leaving the total volume unaffected.

Conclusion:  This work shows that HS-SICM is a versatile tool for resolving rapid morphological changes and volume dynamics of adherent living platelets.

血小板是一种无核细胞,在血管损伤后的伤口闭合过程中发挥着重要作用。保持恒定的血小板体积对血小板功能至关重要。例如,水引起的肿胀可促进促凝活性并引发血栓形成。然而,测量血小板体积变化的技术(如透光率或阻抗技术)有其固有的局限性,因为它们只能进行定性测量或不能在单细胞水平上进行测量。在此,我们引入高速扫描离子电导显微镜(HS-SICM)作为研究单个血小板体积调节机制的新平台。我们对 HS-SICM 进行了优化,使其能以高达 7 秒/帧的扫描速度和 0.1 fL 的精度定量成像附着血小板的形态随时间变化的函数。我们证明,HS-SICM 可以定量测量低渗休克后单个血小板的快速膨胀以及随后的调节容积下降(RVD)。我们发现,与未激活的血小板相比,凝血酶、ADP 和胶原激活的血小板的 RVD 明显降低。应用波义耳-范特霍夫关系,我们可以提取单个血小板的非渗透体积和体积分数。凝血酶或 ADP(而非胶原蛋白)的活化会导致非渗透体积的减少,这可能是由于释放反应造成的,而总体积则不受影响。
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引用次数: 0
The Efficacy and Safety of DOACs in Inherited Antithrombin Deficiency: A Cohort Study from a Tertiary Referral Center. DOACs 对遗传性抗凝血酶缺乏症的疗效和安全性:一家三级转诊中心的队列研究。
IF 5 2区 医学 Q1 HEMATOLOGY Pub Date : 2024-08-21 DOI: 10.1055/a-2379-7288
Caroline Dix, Andrew J Doyle, Karen Breen, Beverley J Hunt

Background:  Individuals with inherited antithrombin deficiency (IATD) have a high risk of venous thromboembolism (VTE). Most VTEs are managed with direct oral anticoagulants (DOACs), but the utility of DOACs in antithrombin deficiency (ATD) is unreported.

Materials and methods:  Patients with IATD treated with DOAC were identified from our institutions' IATD registry. We assessed patients' characteristics, ATD type, and initial VTE characteristics, thrombosis recurrence and bleeding rates.

Results:  Thirty-three patients received DOACs for 73 (38.5-111.5) months (median (interquartile range)). Prior to taking DOACs, 12 (36%) patients had VTE recurrence: these occurred after anticoagulation was ceased (4), nonadherence to VKA prior to DOAC use (3), or during heparin use in pregnancy (5). There were no VTE recurrences on standard-dose DOAC, except in a noncompliant patient receiving dabigatran. There was one recurrence with compliant DOAC use-a patient receiving rivaroxaban 10 mg. Six (18%) patients experienced clinically relevant bleeding, which was predominantly menorrhagia (5/6). One major bleeding event, intracranial hemorrhage, occurred in a patient receiving full-dose rivaroxaban who had refractory hypertension (0.5 events/100 patient-years). In this cohort, compliant DOAC users had an overall VTE recurrence rate of 0.5/100 patient-years, whereas with low-dose DOACs the event rate was 3.5/100 patient-years.

Conclusion:  Standard-dose DOACs appear efficacious and relatively safe in IATD.

遗传性抗凝血酶缺乏症(IATD)患者罹患静脉血栓栓塞症(VTE)的风险很高。大多数 VTE 都是通过直接口服抗凝剂 (DOAC) 治疗的,但 DOAC 在 ATD 中的效用尚未报道。我们从本机构的 IATD 登记册中找到了接受 DOAC 治疗的 IATD 患者。我们评估了患者的特征、ATD类型、初始VTE特征、血栓复发率和出血率。33 名患者接受 DOACs 治疗 73(38.5,111.5)个月(中位数(IQR))。在服用 DOAC 之前,有 12 名患者(36%)出现了 VTE 复发:其中有 4 名患者是在停止抗凝后复发的,有 3 名患者是在服用 DOAC 之前没有坚持使用 VKA,有 5 名患者是在妊娠期使用肝素期间复发的。除了一名接受达比加群治疗的不达标患者外,使用标准剂量 DOAC 的患者没有 VTE 复发。一名接受利伐沙班 10 毫克治疗的患者在遵医嘱使用 DOAC 时出现了一次复发。6名(18%)患者出现了临床相关出血,主要是月经过多(5/6)。一名接受全剂量利伐沙班治疗的难治性高血压患者发生了颅内出血这一重大出血事件(0.5 例/100 患者年)。在该队列中,符合标准剂量的 DOAC 使用者的总体 VTE 复发率为 0.5/100,而低剂量 DOAC 的事件发生率为 3.5/100。总之,标准剂量的 DOACs 在 IATD 中疗效显著且相对安全。
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引用次数: 0
Venous Thromboembolism in Patients with Glioblastoma: Molecular Mechanisms and Clinical Implications. 胶质母细胞瘤患者的静脉血栓栓塞症:分子机制和临床意义。
IF 5 2区 医学 Q1 HEMATOLOGY Pub Date : 2024-08-21 DOI: 10.1055/s-0044-1789592
Maaike Y Kapteijn, Nina Bakker, Johan A F Koekkoek, Henri H Versteeg, Jeroen T Buijs

Patients with glioblastoma are among the cancer patients with the highest risk of developing venous thromboembolism (VTE). Long-term thromboprophylaxis is not generally prescribed because of the increased susceptibility of glioblastoma patients to intracranial hemorrhage. This review provides an overview of the current clinical standard for glioblastoma patients, as well as the molecular and genetic background which underlies the high incidence of VTE. The two main procoagulant proteins involved in glioblastoma-related VTE, podoplanin and tissue factor, are described, in addition to the genetic aberrations that can be linked to a hypercoagulable state in glioblastoma. Furthermore, possible novel biomarkers and future treatment strategies are discussed, along with the potential of sequencing approaches toward personalized risk prediction for VTE. A glioblastoma-specific VTE risk stratification model may help identifying those patients in which the increased risk of bleeding due to extended anticoagulation is outweighed by the decreased risk of VTE.

胶质母细胞瘤患者是罹患静脉血栓栓塞症(VTE)风险最高的癌症患者之一。由于胶质母细胞瘤患者对颅内出血的易感性增加,因此一般不采取长期血栓预防措施。本综述概述了目前针对胶质母细胞瘤患者的临床标准,以及导致 VTE 高发的分子和遗传背景。文章介绍了参与胶质母细胞瘤相关 VTE 的两种主要促凝蛋白 podoplanin 和组织因子,以及可能与胶质母细胞瘤高凝状态有关的基因畸变。此外,还讨论了可能的新型生物标记物和未来的治疗策略,以及个性化 VTE 风险预测测序方法的潜力。胶质母细胞瘤特异性 VTE 风险分层模型可能有助于确定哪些患者因延长抗凝时间而增加的出血风险大于 VTE 风险的降低。
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引用次数: 0
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Thrombosis and haemostasis
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