Blood Vessels, Thrombosis & Hemostasis最新文献_第3页

Automated natural language processing to identify venous thromboembolism from diagnostic imaging reports 从诊断成像报告中识别静脉血栓栓塞的自动自然语言处理

Blood Vessels, Thrombosis & Hemostasis

Pub Date : 2025-10-28 DOI: 10.1016/j.bvth.2025.100122

Naveen Subramanian , Hector Garcia Pleitez , Daniel Nguyen , Denái R. Milton , Partow Kebriaei , Elizabeth Shpall , Lee Cheng , Jing Lu , Shida Jin , Carol C. Wu , Rahul A. Sheth , Alessandra Ferrajoli , Katy M. Toale , Michael H. Kroll , Cristhiam M. Rojas-Hernandez

Abstract

The annual incidence of venous thromboembolism (VTE) may be 50-fold increased after allogeneic hematopoietic stem cell transplant (HSCT). Such incidence data, as well as data that establish clinical variables resulting in this enhanced risk, have generally required manual chart review. This cumbersome process can be improved by natural language processing (NLP) algorithms designed to detect VTE in electronic medical record systems. We describe the development of an institutional NLP algorithm for VTE detection, and our evaluation of its performance in detecting VTE in patients who recently underwent HSCT. We retrospectively reviewed adult patients between 2016 and 2020. NLP assessed patient records for acute VTE within 100 days of HSCT, and manual chart review was performed for comparison. NLP sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) were calculated. A total of 1300 electronic health records were analyzed. The 100-day VTE incidence rate as determined via manual chart review and NLP was 10.3% and 8.8%, respectively. NLP’s specificity, sensitivity, PPV, and NPV were >0.85. Of the 19 events not identified by NLP, all were found in radiology or vascular laboratory reports overlooked by NLP. These results demonstrate excellent performance of NLP for identifying VTE in HSCT patients. Future refinement of NLP, and its combination with other detection methods should provide better detection of VTE in this and other at-risk cohorts.

摘要同种异体造血干细胞移植（HSCT）后静脉血栓栓塞（VTE）的年发病率可能增加50倍。这种发病率数据，以及建立导致这种风险增加的临床变量的数据，通常需要手工检查图表。这个繁琐的过程可以通过自然语言处理（NLP）算法来改进，该算法设计用于检测电子医疗记录系统中的静脉血栓栓塞。我们描述了一种用于静脉血栓栓塞检测的机构NLP算法的发展，以及我们对其在最近接受了HSCT的患者中检测静脉血栓栓塞的性能的评估。我们回顾性地回顾了2016年至2020年的成年患者。NLP评估了HSCT术后100天内急性静脉血栓栓塞的患者记录，并进行了手工图表回顾以进行比较。计算NLP的敏感性、特异性、阳性预测值（PPV）和阴性预测值（NPV）。共分析了1300份电子健康记录。通过手工图表检查和NLP确定的100天静脉血栓栓塞发生率分别为10.3%和8.8%。NLP的特异性、敏感性、PPV和NPV均为>；0.85。在NLP未发现的19个事件中，所有事件都是在被NLP忽略的放射学或血管实验室报告中发现的。这些结果表明NLP在鉴别HSCT患者的静脉血栓栓塞方面表现优异。未来对NLP的改进，以及与其他检测方法的结合，应该能更好地检测出这一人群和其他高危人群的静脉血栓栓塞。

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引用次数: 0

Treatment of canine hemophilia A via intraosseous delivery of a platelet-specific factor VIII–lentiviral vector 血小板特异性因子viii -慢病毒载体骨内递送治疗犬血友病A

Blood Vessels, Thrombosis & Hemostasis

Pub Date : 2025-10-24 DOI: 10.1016/j.bvth.2025.100119

Cameron W. Rementer ∗ , Chong Li ∗ , Timothy C. Nichols , Xiaohe Cai , Julia Joo , Xuefeng Wang , Mark Kloos , Nneka George , Ting-Yen Chao , Yuanyi Xu , Mortimer Poncz , Hans D. Ochs , David J. Rawlings , Carol H. Miao

Abstract

Hemophilia A (HemA) is a genetic disease resulting from a factor VIII (FVIII) deficiency. Traditional protein infusions to treat HemA are costly and inconvenient and require repeated dosing. We demonstrated previously that intraosseous (IO) gene therapy via delivery of lentiviral vectors (LVs) into bone marrow targeting FVIII expression in platelets successfully treated HemA mice. To facilitate the translation of this novel strategy to clinical application, we investigated the treatment of HemA dogs using IO gene therapy. The vesicular stomatitis virus–pseudotyped G-cF8-LV incorporating a platelet-specific promoter, Gp1bα, and canine F8 gene was injected into the tibia or iliac bones of 4 HemA dogs. All dogs recovered well from the procedure and had blood chemistry values within normal ranges. Canine FVIII can be detected in platelets with the highest expression ∼40 to 50 days after the procedure, and the expression persisted for the experimental duration in all treated dogs. Copy numbers of the transgene were persistently detected from the genomic DNA isolated from peripheral mononuclear blood cells. The shortened whole-blood clotting time and improved parameters evaluated through thromboelastography testing at multiple time points indicated improved hemostasis after gene therapy. Furthermore, the IO gene therapy was well tolerated and did not produce any toxicity in the treated dogs. Most significantly, the treated dogs experienced fewer bleeding events per year after gene therapy than before. Our study demonstrated a potentially safe and effective in vivo gene therapy strategy for treating people with HemA.

血友病A （HemA）是一种由因子VIII （FVIII）缺乏引起的遗传病。传统的蛋白输注治疗血HemA既昂贵又不方便，而且需要反复给药。我们之前证明，通过将慢病毒载体（lv）递送到骨髓中靶向血小板中FVIII表达的骨内（IO）基因治疗成功治疗了HemA小鼠。为了促进这种新策略的临床应用，我们研究了使用IO基因疗法治疗HemA犬。将含有血小板特异性启动子Gp1bα和犬F8基因的水泡性口炎病毒假型G-cF8-LV注射到4只HemA犬的胫骨或髂骨中。所有的狗都从手术中恢复良好，血液化学值在正常范围内。犬FVIII可在血小板中检测到，在手术后40至50天达到最高表达，并且在所有治疗犬的实验期间均持续表达。从外周血单核细胞分离的基因组DNA中持续检测到转基因的拷贝数。全血凝血时间缩短，多个时间点血栓弹性成像指标改善，表明基因治疗后止血改善。此外，IO基因疗法耐受性良好，对接受治疗的狗没有产生任何毒性。最重要的是，经过基因治疗的狗每年的出血事件比之前少。我们的研究证明了一种潜在安全有效的体内基因治疗策略可以治疗HemA患者。

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引用次数: 0

Sustained expression of hemopexin in an animal model of sickle cell anemia 镰状细胞性贫血动物模型中血凝素的持续表达

Blood Vessels, Thrombosis & Hemostasis

Pub Date : 2025-10-22 DOI: 10.1016/j.bvth.2025.100115

Franciele De Lima , Carla Roberta Peachazepi De Moraes , Ivanio Teixeira Borba-Junior , Heloísa Balan Assalin , Mario José Abdalla Saad , Fernando Ferreira Costa , Erich V. De Paula

Abstract

Sickle cell disease is a condition characterized by vaso-occlusive episodes and sustained hemolysis, leading to a chronic inflammatory state. Several studies have shown that the release of heme to the extracellular space due to hemolysis contributes to the inflammatory cascade observed in these patients. Hemopexin (HPX), the molecule responsible for removing excess heme from the circulation, is depleted in these patients. We have previously demonstrated that the IV infusion of an adeno-associated virus–based gene transfer vector was capable of inducing the transgenic expression of HPX in a dose-dependent manner in C57Bl6 mice. Here, we explored the effect of this vector in a mouse model of sickle cell anemia. Townes mice were transduced with 2 × 10¹³ vector genomes per kilogram and followed up for up to 48 weeks. HPX expression was confirmed in liver samples by both western blot and quantitative polymerase chain reaction (HPX), but gene transfer did not restore circulating levels of HPX in Townes mice, as shown in models without hemolysis. Indirect surrogate markers of a beneficial effect of delivering HPX were observed, including increased expression of heme-oxygenase 1 upon heme overload, greater weight gain on the long-term follow-up, and a significant decrease in tumor necrosis factor α levels. No signs of liver or hematological toxicity were observed. Our results demonstrate the potential and challenges of therapeutic strategies based on the long-term delivery of HPX in an animal model of sickle cell anemia.

镰状细胞病是一种以血管闭塞发作和持续溶血为特征的疾病，导致慢性炎症状态。几项研究表明，由于溶血，血红素释放到细胞外空间有助于这些患者观察到的炎症级联反应。血红素（HPX）是一种负责从血液循环中去除过量血红素的分子，在这些患者中被耗尽。我们之前已经证明，静脉输注基于腺相关病毒的基因转移载体能够在C57Bl6小鼠中以剂量依赖的方式诱导HPX的转基因表达。在这里，我们探索了该载体在镰状细胞性贫血小鼠模型中的作用。用每公斤2 × 1013个载体基因组对Townes小鼠进行转导，随访48周。western blot和定量聚合酶链反应（quantitative polymerase chain reaction， HPX）证实HPX在肝脏样本中表达，但在没有溶血的模型中，基因转移并没有恢复Townes小鼠循环中HPX的水平。我们观察到传递HPX有益效果的间接替代标记物，包括血红素超载时血红素加氧酶1的表达增加，长期随访时体重增加，肿瘤坏死因子α水平显著降低。没有观察到肝脏或血液毒性的迹象。我们的研究结果证明了基于镰状细胞性贫血动物模型长期递送HPX的治疗策略的潜力和挑战。

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引用次数: 0

The small-molecule Syk inhibitor R788 inhibits hematopoiesis and worsens anemia in sickle cell disease mice 小分子Syk抑制剂R788抑制造血并加重镰状细胞病小鼠的贫血

Blood Vessels, Thrombosis & Hemostasis

Pub Date : 2025-10-16 DOI: 10.1016/j.bvth.2025.100118

Bindu Parachalil Gopalan , Sayuri Kamimura , Pradeep Dagur , Duck-Yeon Lee , Niharika Shah , Martha Quezado , Zenaide Quezado ∗ , Arun S. Shet ∗

Abstract

Vaso-occlusive crises, thrombosis, inflammation, and immune dysregulation contribute to organ damage and poor outcomes in sickle cell disease (SCD). Because neutrophils and dysregulated extracellular trap formation (NETosis) contribute to sickle pathophysiology, and the spleen tyrosine kinase (Syk) signaling pathway is a key driver of NETosis, we investigated the effect of targeting Syk with fostamatinib (R788). Specifically, we studied the effect of a selective Syk inhibitor, R788, on hematologic and biochemical parameters, NETosis, platelet P-selectin expression, and platelet-neutrophil aggregate formation in Townes sickle mice at baseline and after exposure to pathophysiological stressors (tumor necrosis factor α [TNF-α] and hypoxia-reoxygenation). Our results showed that at baseline R788 impaired hematopoiesis, and worsened anemia and neutropenia in sickle mice. Additionally, R788 at nontoxic doses had little, if any, effect on NETosis and platelet activation induced by TNF-α or hypoxia-reoxygenation. Severe anemia and neutropenia induced by R788 in the sickle mouse model suggests that concomitant use of Syk inhibitors with hydroxyurea in patients with SCD should be approached cautiously. Further research is required to clarify the benefits and risks of selective Syk inhibition in SCD and other hemolytic conditions exhibiting stress hematopoiesis.

血管闭塞危象、血栓形成、炎症和免疫失调导致镰状细胞病（SCD）的器官损伤和不良预后。由于中性粒细胞和失调的细胞外陷阱形成（NETosis）有助于镰状病病理生理，而脾脏酪氨酸激酶（Syk）信号通路是NETosis的关键驱动因素，我们研究了fostamatinib靶向Syk的效果（R788）。具体来说，我们研究了选择性Syk抑制剂R788在基线和暴露于病理生理应激源（肿瘤坏死因子α [TNF-α]和缺氧再氧化）后对汤斯镰状小鼠血液学和生化参数、NETosis、血小板p -选择素表达和血小板中性粒细胞聚集形成的影响。我们的研究结果显示，在基线R788损害造血功能，加重贫血和中性粒细胞减少的镰状小鼠。此外，无毒剂量的R788对TNF-α或缺氧再氧化诱导的NETosis和血小板活化几乎没有影响。R788在镰状小鼠模型中引起的严重贫血和中性粒细胞减少，提示在SCD患者中同时使用Syk抑制剂和羟基脲应谨慎对待。需要进一步的研究来阐明选择性Syk抑制在SCD和其他表现应激性造血的溶血性疾病中的益处和风险。

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引用次数: 0

Risk factors for anticoagulant-related bleeding in cancer: traditional and cancer-specific factors 癌症抗凝相关出血的危险因素：传统因素和癌症特异性因素

Blood Vessels, Thrombosis & Hemostasis

Pub Date : 2025-10-09 DOI: 10.1016/j.bvth.2025.100116

Alexa Loncharich , Brian F. Gage , Suhong Luo , Martin Schoen , Amber Afzal , Amir Mahmoud , Kenneth Carson , Su-Hsin Chang , Yan Yan , Kristen M. Sanfilippo

Abstract

Managing anticoagulant therapy in cancer-associated venous thromboembolism (VTE) is challenging due to risks of recurrent VTE and anticoagulant-related bleeding. Existing clinical risk models for bleeding are limited by discriminatory ability in patients with cancer, perhaps due to the omission of cancer-specific risk factors for bleeding. This study estimated the associations of traditional and cancer-specific risk factors with bleeding requiring hospitalization in patients with cancer-associated VTE prescribed anticoagulant therapy. We conducted a retrospective cohort study using the Veterans Health Administration database to identify patients with cancer-associated VTE between 2012 and 2020. Cancer-associated VTE was defined by diagnostic International Classification of Diseases codes and the prescription of anticoagulant therapy within 30 days of VTE. The primary outcome was bleeding resulting in hospitalization. Traditional and cancer-specific risk factors were assessed using the methods of Fine and Gray, with death as a competing event. Among 11 151 patients with cancer-associated VTE, 869 patients (8.5%) experienced bleeding within 12 months of anticoagulant therapy. The most common bleeding sites were gastrointestinal (56.3%) and genitourinary tract (20.1%). Significant risk factors included age, alcohol abuse, anemia, liver injury or disease, uncontrolled hypertension, and history of bleeding. Cancer-specific risk factors included site of cancer, metastatic disease, and systemic cancer therapy. This study identifies readily available clinical risk factors associated with anticoagulant-related bleeding requiring hospitalization in patients with cancer-associated VTE. Among the identified variables, some could be considered modifiable. Identification and mitigation of risk factors for anticoagulant-related bleeding could guide management of anticoagulant therapy in this high-risk patient population.

摘要肿瘤相关性静脉血栓栓塞（VTE）的抗凝治疗管理具有挑战性，因为VTE复发和抗凝相关出血的风险。现有的临床出血风险模型受到癌症患者的区分能力的限制，可能是由于遗漏了癌症特异性的出血危险因素。本研究估计了传统和癌症特异性危险因素与癌症相关性静脉血栓栓塞患者需要住院治疗的出血之间的关系。我们使用退伍军人健康管理局的数据库进行了一项回顾性队列研究，以确定2012年至2020年间患有癌症相关静脉血栓栓塞的患者。通过诊断性国际疾病分类代码和静脉血栓栓塞30天内抗凝治疗处方来定义癌症相关静脉血栓栓塞。主要结果是出血导致住院。使用Fine和Gray方法评估传统和癌症特异性风险因素，并将死亡作为竞争事件。在11151例癌症相关性静脉血栓栓塞患者中，869例（8.5%）患者在抗凝治疗12个月内出现出血。最常见的出血部位为胃肠道（56.3%）和泌尿生殖系统（20.1%）。重要的危险因素包括年龄、酗酒、贫血、肝损伤或疾病、未控制的高血压和出血史。癌症特异性危险因素包括癌症部位、转移性疾病和全身癌症治疗。本研究确定了与癌症相关性静脉血栓栓塞患者需要住院治疗的抗凝相关出血相关的临床危险因素。在确定的变量中，有些可以被认为是可修改的。识别和减轻抗凝相关出血的危险因素可以指导这一高危患者群体的抗凝治疗管理。

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引用次数: 0

High incidence of thrombin generation resistance to thrombomodulin in patients with unprovoked venous thromboembolism 无因性静脉血栓栓塞患者凝血酶生成对血栓调节素耐药的高发

Blood Vessels, Thrombosis & Hemostasis

Pub Date : 2025-10-09 DOI: 10.1016/j.bvth.2025.100117

Jean-Christophe Gris , Mathias Chea , Eva Nouvellon , Raphaël De Jouvancourt , Mathieu Fortier , Chloé Bourguignon , Jeremy Laurent , Sylvie Bouvier , Antonia Perez-Martin

Abstract

Poorly controlled thrombin generation (TG) can induce venous thromboembolism (VTE). Assessing the global coagulation potential may help to characterize the risk of VTE. TG assay (TGA) quantifying the endogenous thrombin potential (ETP) and its inhibition after adding purified thrombomodulin (TM) allows certain thrombotic phenotypes to be recognized. We tested the TM-induced ETP variation in 989 uncoagulated patients with their first unprovoked VTE and 200 controls using an automated TGA and commercially available reagents. We found evidence of ETP resistance to TM, defined at the fifth percentile value found in controls, in 406 patients (41.1%, P < .0001), mixing tests in patients who were antiphospholipid antibody-negative showing no inhibitory activity. We investigated the 422 patients with full clinical and laboratory information for predictors of ETP resistance to TM (R-ETP/TM), found positive in 163 of them (38.6%). Multivariate analysis showed that D-dimers were positive, protein S and Rosner index were negative risk factors for R-ETP/TM (quantitative model), high D-dimers and factor VIII, protein C <65 IU, and protein S <50 IU were risk factors (qualitative model). The scores derived had insufficient predictive performances to diagnose R-ETP/TM, which is a frequent plasma phenotype in patients with unprovoked VTE. The complete identification of its determinants deserves further investigation.

摘要控制不良的凝血酶生成可诱发静脉血栓栓塞。评估总凝血电位可能有助于确定静脉血栓栓塞的风险。TG测定（TGA）定量内源性凝血酶电位（ETP）及其在加入纯化的血栓调节素（TM）后的抑制作用，使某些血栓表型得以识别。我们使用自动TGA和市售试剂检测了989例首次无诱发性静脉血栓栓塞的未凝患者和200例对照患者中tm诱导的ETP变异。我们在406例患者（41.1%,P < .0001）中发现了ETP对TM耐药的证据，在抗磷脂抗体阴性的患者中进行混合试验，显示没有抑制活性。我们调查了422例具有完整临床和实验室信息的ETP对TM耐药预测因子（R-ETP/TM），其中163例（38.6%）呈阳性。多因素分析显示d -二聚体阳性，蛋白S和Rosner指数为R-ETP/TM的负相关危险因素（定量模型），高d -二聚体和因子VIII、蛋白C和蛋白S为65 IU，蛋白S和50 IU为危险因素（定性模型）。获得的评分不足以预测R-ETP/TM的诊断，R-ETP/TM是非诱发性静脉血栓栓塞患者常见的血浆表型。它的决定因素的完全确定值得进一步的研究。

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引用次数: 0

The role of hemoglobin F in sickle cell disease complications: a descriptive secondary analysis 血红蛋白F在镰状细胞病并发症中的作用：描述性二次分析

Blood Vessels, Thrombosis & Hemostasis

Pub Date : 2025-10-09 DOI: 10.1016/j.bvth.2025.100114

Heath Aston , Elexis Price , Elena Wernecke , Emma Hazenberg , Daniel Herrera , Siera Gollan , Hongyan Xu , Girindra Raval , Abdullah Kutlar

Abstract

Individuals with sickle cell disease (SCD), a prevalent inherited blood disorder, are at increased risk for tissue ischemia and thrombosis secondary to sickle hemoglobin polymerization. Fetal hemoglobin (HbF) protects against the vaso-occlusive nature of sickled erythrocytes. Our study aims to investigate the association between HbF level and various SCD complications. The study used a descriptive and cross-sectional design to analyze existing, secondary medical record data of 496 patients with SCD who received care from the Center for Blood Disorders in Augusta, Georgia. Of these, only patients with HbSS and an HbSβ0 thalassemia (n = 273) were included in the analysis. Data abstraction included history of thrombotic event (TE) and HbF values closest to the TE, along with presence of SCD clinical complications, use of anticoagulation medications, specific laboratory values, and Hb electrophoresis. These patients were reflective of the greater population of patients with SCD in that they had similar rates of complications such as avascular necrosis and sickle cell retinopathy compared with nationally reported data. We found a significant association between incidence of thrombosis and higher HbF levels (P = .034). The presence of HbF was also found to influence the incidence of complications, including avascular necrosis and pulmonary hypertension. When stratified into quantiles, there was a relationship between HbF and incidence of AVN in male patients (P = .038). Further research is warranted to investigate whether other treatments for SCD produce similar results and whether this effect is representative of other large patient populations with SCD.

摘要镰状细胞病（SCD）是一种常见的遗传性血液疾病，镰状血红蛋白聚合引起的组织缺血和血栓形成的风险增加。胎儿血红蛋白（HbF）对镰状红细胞的血管闭塞性有保护作用。我们的研究旨在探讨HbF水平与各种SCD并发症之间的关系。该研究采用描述性和横断面设计来分析496名SCD患者的现有二级医疗记录数据，这些患者接受了乔治亚州奥古斯塔血液疾病中心的治疗。其中，只有HbSS和HbSβ0型地中海贫血患者（n = 273）被纳入分析。数据包括血栓形成事件（TE）的历史和最接近TE的HbF值，以及SCD临床并发症的存在，抗凝药物的使用，特定实验室值和Hb电泳。这些患者反映了更多的SCD患者群体，因为与全国报道的数据相比，他们有相似的并发症发生率，如缺血性坏死和镰状细胞视网膜病变。我们发现血栓发生率与HbF水平升高之间存在显著关联（P = 0.034）。HbF的存在也会影响并发症的发生率，包括缺血性坏死和肺动脉高压。当分层到分位数时，HbF与男性患者AVN发生率之间存在相关性（P = 0.038）。需要进一步的研究来调查其他治疗SCD是否产生类似的结果，以及这种效果是否代表其他大型SCD患者群体。

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引用次数: 0

DOACs vs warfarin in AF with comorbid CKD or valvular disease: a systematic review and meta-analysis DOACs vs华法林治疗合并CKD或瓣膜疾病的房颤：一项系统回顾和荟萃分析

Blood Vessels, Thrombosis & Hemostasis

Pub Date : 2025-10-07 DOI: 10.1016/j.bvth.2025.100111

Aileen Liang , Cathy Wang , Alla E. Iansavitchene , Alejandro Lazo-Langner

Abstract

Direct oral anticoagulant agents (DOACs) are indicated to prevent vascular events in patients with atrial fibrillation (AF) without concomitant valvular disease or severe chronic kidney disease (CKD), groups in which warfarin is the preferred choice. We aimed to evaluate the safety of DOACs in these populations compared to warfarin. We conducted a systematic review in MEDLINE, Embase, and Evidence Based Medicine Reviews to identify randomized-controlled trials (RCTs) and non-RCTs assessing warfarin or DOACs (rivaroxaban, dabigatran, apixaban, or edoxaban) in patients with AF with concomitant valvular disease or CKD (according to Kidney Disease Outcomes Quality Initiative guidelines) that reported on bleeding, stroke, or systemic/arterial thromboembolism. Meta-analysis was performed for eligible studies using the Mantel-Haenszel method random effects model. Of 3172 screened studies, we included 110 studies (310 478 patients with concomitant AF and CKD; 99 299 patients with concomitant AF and valve disease). Meta-analysis showed that, compared to warfarin, in patients with concomitant AF and CKD, DOACs were associated with reduced bleeding (odds ratio [OR], 0.66; 95% confidence interval [Cl], 0.49-0.88; P = .005) and strokes (OR, 0.60; 95% CI, 0.43-0.85; P = .004), particularly in patients with stages 4 and 5 CKD and dialysis patients. In patients with concomitant AF and valvular disease, DOACs were associated with reduced bleeding (OR, 0.75; 95% CI, 0.57-0.97; P = .03) and stroke incidence (OR, 0.66; 95% CI, 0.47-0.93; P = .02). Differences were noted for RCTs and non-RCTs. Our findings suggest that DOACs may be equivalent or superior to warfarin both in the prevention of thromboembolic events and reduction of bleeding in these patients.

【摘要】直接口服抗凝药物（DOACs）可以预防心房颤动（AF）患者的血管事件，但不伴有瓣膜疾病或严重慢性肾脏疾病（CKD），其中华法林是首选。我们的目的是评估doac与华法林在这些人群中的安全性。我们在MEDLINE、Embase和循证医学评论中进行了系统回顾，以确定评估华法林或doac（利伐沙班、达比加群、阿哌沙班或依多沙班）在伴有瓣膜疾病或CKD（根据肾病结局质量计划指南）的房颤患者中（报告出血、卒中或全身/动脉血栓栓塞）的随机对照试验（rct）和非rct。采用Mantel-Haenszel方法随机效应模型对符合条件的研究进行meta分析。在筛选的3172项研究中，我们纳入了110项研究（310478例合并房颤和CKD患者；99299例合并房颤和瓣膜疾病患者）。荟萃分析显示，与华法林相比，在合并AF和CKD的患者中，DOACs与出血减少（优势比[OR]， 0.66； 95%可信区间[Cl]， 0.49-0.88; P = 0.005）和卒中（OR, 0.60; 95% CI, 0.43-0.85; P = 0.004）相关，特别是在4期和5期CKD患者和透析患者中。在伴有房颤和瓣膜疾病的患者中，DOACs与出血减少（OR, 0.75; 95% CI, 0.57-0.97; P = 0.03）和卒中发生率相关（OR, 0.66; 95% CI, 0.47-0.93; P = 0.02）。在随机对照试验和非随机对照试验中存在差异。我们的研究结果表明，DOACs在预防这些患者的血栓栓塞事件和减少出血方面可能相当于或优于华法林。

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引用次数: 0

Limited availability of variant-specific germ line data creates challenges in the interpretation of myeloid NGS panels 变异特异性生殖系数据的有限可用性为髓系NGS面板的解释带来了挑战

Blood Vessels, Thrombosis & Hemostasis

Pub Date : 2025-10-06 DOI: 10.1016/j.bvth.2025.100113

Aaron Jacob Winer , Emily F. Mason , Alexander G. Bick , Michael R. Savona , Ashwin Kishtagari

Abstract

ANKRD26-related thrombocytopenia (ANKRD26-RT) is a rare inherited platelet disorder that carries an increased predisposition to hematologic malignancy. We report the case of an unprovoked thrombus in a patient with anemia, who was discovered to have an ANKRD26 germ line variant of uncertain significance (VUS), along with a 20q chromosomal deletion. This patient’s variant lies downstream of the recognized mutational hot spot known to be associated with thrombocytopenia and myeloid neoplasms and, as a VUS, is not definitively diagnostic of ANKRD26-RT. In this case, the del(20q) supports the notion of somatic chromosomal abnormality in the context of unexplained anemia, suggestive of clonal cytopenia of undetermined significance (CCUS). Although 3 known cases of thrombosis have been reported in patients with ANKRD26-RT, there is no known association with hypercoagulability. The role of the ANKRD26 VUS reported in this case vis-à-vis the patient’s hypercoagulability and CCUS remains unclear. This case raises the question of whether hypercoagulability should be added to the expanding phenotypic spectrum of ANKRD26-related disorders, highlights the challenges of interpreting and managing unexpected germ line findings, and underlines the importance of contributing to genetic variant databases to optimize variant calling and recommendations for patients.

tankrd26相关性血小板减少症（ANKRD26-RT）是一种罕见的遗传性血小板疾病，携带血液恶性肿瘤易感性增加。我们报告一例无因性血栓患者的贫血，谁被发现有ANKRD26生殖系变异不确定的意义（VUS），连同20q染色体缺失。该患者的变异位于已知与血小板减少症和髓系肿瘤相关的公认突变热点的下游，作为一种VUS，不能明确诊断ANKRD26-RT。在这种情况下，del（20q）支持了在不明原因贫血背景下体细胞染色体异常的概念，暗示了未确定意义的克隆性细胞减少症（CCUS）。虽然有3例已知的ANKRD26-RT患者血栓形成的报告，但没有已知的与高凝性的关联。本病例中报道的ANKRD26 VUS在-à-vis患者高凝性和CCUS中的作用尚不清楚。该病例提出了一个问题，即是否应该将高凝性添加到ankrd26相关疾病的不断扩大的表型谱中，突出了解释和管理意外生殖系发现的挑战，并强调了贡献遗传变异数据库以优化变异召唤和患者建议的重要性。

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引用次数: 0

Mitochondrial arginase 2 regulates hematopoietic and cardiovascular adaptation to hypoxia 线粒体精氨酸酶2调节造血和心血管对缺氧的适应

Blood Vessels, Thrombosis & Hemostasis

Pub Date : 2025-10-06 DOI: 10.1016/j.bvth.2025.100110

Weiling Xu , Kewal Asosingh , Allison J. Janocha , Evan Madden , Nicholas Wanner , Dylan Trotter , Michael V. Novotny , Anny Mulya , Ruoying Chen , Samar Farha , Serpil C. Erzurum

Abstract

Physiological adaptation to hypoxia involves coordinated responses of the hematopoietic and cardiovascular systems to maintain tissue oxygenation. Arginine metabolism, via nitric oxide synthases and arginases, modulates both erythropoiesis and vascular tone. Arginase 2 (Arg2), a mitochondrial enzyme, may regulate these responses by limiting arginine availability for nitric oxide (NO) production. We hypothesized that deletion of Arg2 (Arg2 knockout [Arg2KO]) would augment NO bioavailability, attenuate hypoxia-driven hematopoiesis, and protect against pulmonary vascular remodeling. To test this, we exposed Arg2KO and wild-type (WT) mice to normoxia, short-term (6-72 hours) or chronic (3 weeks) hypoxia. In comparison with WT, Arg2KO mice under normoxia had fewer erythroid progenitors, comparable hematologic and cardiovascular parameters, but greater numbers of small vessels in the lungs. Under short-term hypoxia, Arg2KO mice had a blunted erythropoietic response, with elevated plasma arginine and NO metabolites as compared with WT mice. Under chronic hypoxia, WT mice developed elevated right ventricular systolic pressure (RVSP) and remodeling of small pulmonary vessels. In contrast, Arg2KO mice did not increase RVSP or small vessel remodeling and maintained lower systemic blood pressure and heart rate compared with WT mice. Metabolically, endothelial cells from Arg2KO mice lungs demonstrated upregulation of arginine biosynthetic and fatty acid β-oxidation pathways, accompanied by less myocardial lipid droplet accumulation. These findings identify a previously unrecognized role for mitochondrial ARG2 in regulating hematopoietic and vascular adaptation to hypoxia through modulation of nitric oxide signaling and metabolic reprogramming.

对缺氧的生理适应涉及造血系统和心血管系统的协调反应，以维持组织氧合。精氨酸代谢，通过一氧化氮合酶和精氨酸酶，调节红细胞生成和血管张力。精氨酸酶2 (Arg2)，一种线粒体酶，可能通过限制精氨酸对一氧化氮（NO）产生的可用性来调节这些反应。我们假设Arg2的缺失（Arg2敲除[Arg2KO]）会增加NO的生物利用度，减弱缺氧驱动的造血，并保护肺血管重构。为了验证这一点，我们将Arg2KO和野生型（WT）小鼠暴露于常氧、短期（6-72小时）或慢性（3周）缺氧环境中。与WT相比，正常缺氧条件下的Arg2KO小鼠红细胞祖细胞较少，血液学和心血管参数相似，但肺部小血管数量较多。在短期缺氧条件下，Arg2KO小鼠的红细胞生成反应减弱，血浆精氨酸和NO代谢产物与WT小鼠相比升高。在慢性缺氧条件下，WT小鼠右心室收缩压升高，肺小血管重构。相比之下，Arg2KO小鼠与WT小鼠相比，没有增加RVSP或小血管重塑，并保持较低的全身血压和心率。代谢方面，Arg2KO小鼠肺内皮细胞显示精氨酸生物合成和脂肪酸β-氧化途径上调，同时心肌脂滴积累减少。这些发现表明，线粒体ARG2通过调节一氧化氮信号和代谢重编程，在调节造血和血管对缺氧的适应中发挥了以前未被认识到的作用。

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引用次数: 0