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Inflammatory pathways in transfusion-associated circulatory overload 输血相关循环负荷中的炎症途径

Blood Vessels, Thrombosis & Hemostasis

Pub Date : 2025-08-01 DOI: 10.1016/j.bvth.2025.100080

RoseAnn E. Vik ∗ , Esther B. Bulle ∗ , Wilmore C. Webley , Paul Visintainer , Samantha Ramirez , Peter St. Marie , Theresa Stec , Lynne O’Hearn , Chester Andrzejewski Jr. † , Alexander P. J. Vlaar †

Abstract

Transfusion-associated circulatory overload (TACO) is a leading cause of transfusion-associated mortality. TACO is thought to result from hydrostatic forces in the vascular space, leading to transudative pulmonary edema. Recent studies suggest that TACO is not solely a volume overload phenomenon, but may involve inflammatory processes. This study aimed to further explore the presence of inflammation in patients with TACO. We conducted a retrospective study with 3 cohorts receiving red blood cell transfusion: (1) patients having TACO as defined by a national hemovigilance case surveillance classification (conventional TACO [cTACO], n = 33); (2) patients having symptoms consistent with TACO but not completely meeting reporting criteria (institutional TACO [iTACO], n = 33); and (3) a patient cohort who experienced uncomplicated transfusions (n = 6). Samples from before transfusion, after transfusion, and 8 to 36 hours after transfusion were examined. Samples were analyzed for levels of tumor necrosis factor α, interleukin-1α (IL-1α), IL-6, IL-8, IL-10, C-reactive protein, intercellular adhesion molecule 1 (ICAM-1), vascular cell adhesion molecule 1, atrial natriuretic peptide, cardiac troponin, and N-terminal pro–B-type natriuretic peptide. Patients with cTACO and iTACO had an elevated body temperature, higher heart rate, and lower oxygen saturation after transfusion, whereas only patients with cTACO had higher blood pressures. Levels of key proinflammatory cytokines, IL-6, and IL-8 were elevated in patients with cTACO and iTACO after transfusion, whereas ICAM-1 was elevated only in patients with iTACO after transfusion. Our results suggest that inflammatory pathways may be invoked in patients with TACO. Patients with iTACO showed a more distinctive inflammatory profile, suggesting a gray area between transfusion-related acute lung injury and TACO.

输血相关循环负荷（TACO）是输血相关死亡的主要原因。TACO被认为是由血管间隙的流体静力引起的，导致肺水肿。最近的研究表明，TACO不仅仅是一种体积超载现象，而且可能涉及炎症过程。本研究旨在进一步探讨TACO患者是否存在炎症。我们对接受红细胞输血的3个队列进行了回顾性研究：(1)根据国家血液警戒病例监测分类（传统TACO [cTACO]， n = 33）定义的TACO患者；(2)症状符合TACO但不完全符合报告标准的患者（机构TACO [iTACO]， n = 33）；(3)经历无并发症输血的患者队列（n = 6）。检查输血前、输血后和输血后8至36小时的样本。分析肿瘤坏死因子α、白细胞介素-1α (IL-1α)、IL-6、IL-8、IL-10、c反应蛋白、细胞间粘附分子1 （ICAM-1）、血管细胞粘附分子1、心房钠肽、心肌肌钙蛋白和n端前b型钠肽的水平。cTACO和iTACO患者输血后体温升高，心率升高，血氧饱和度降低，而只有cTACO患者血压升高。输血后，cTACO和iTACO患者的关键促炎细胞因子、IL-6和IL-8水平升高，而ICAM-1仅在iTACO患者中升高。我们的研究结果表明，炎症途径可能在TACO患者中被调用。iTACO患者表现出更独特的炎症特征，表明输血相关急性肺损伤与TACO之间存在灰色地带。

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引用次数: 0

Nasal RADA16 hydrogel application decreases epistaxis severity scores in adults with hereditary hemorrhagic telangiectasia 鼻腔应用RADA16水凝胶可降低遗传性出血性毛细血管扩张的成人鼻出血严重程度评分

Blood Vessels, Thrombosis & Hemostasis

Pub Date : 2025-07-25 DOI: 10.1016/j.bvth.2025.100098

Avraham Adelman , Eunice Im , Lindsey Jackson , Anil Patel , Nikita Chapurin , Christina Eagan , Ali Ataya , Marc Zumberg , Jennifer K. Mulligan , Carl Atkinson , Brian C. Lobo , Jeb M. Justice

Abstract

More than 90% of adults with hereditary hemorrhagic telangiectasia (HHT) experience epistaxis, which can be recurrent and cause significant morbidity. RADA16 is a self-assembling peptide hydrogel approved by the US Food and Drug Administration for hemostasis and wound healing. In this cohort study, we assessed the effectiveness of nasal RADA16 application in controlling HHT-related epistaxis. A retrospective chart review was performed on a cohort of adult patients who received nasal RADA16 without any other changes in treatment. Pre- and post-Epistaxis Severity Scores (ESS), hemoglobin, and hematocrit were collected to assess treatment response. Of the included patients (n = 22), there were 26 applications of RADA16. The cohort was 54.5% male and 86.4% White, had a mean age of 55.5 years, and had a predominantly ACVRL1 genotype (40.9%). Baseline mean ESS was 5.0 and decreased by an average of 2.0 at an average of 46.9 days after treatment, which is 2.8 times more than the minimal clinically important difference for ESS in HHT (0.71). The mean baseline hemoglobin (n = 13) and hematocrit (n = 10), were 11.3 g/dL and 37.5%, respectively, and did not exhibit significant changes after RADA16 application. No bleeding, pain, or allergic reactions occurred due to the application. Several patients reported mild nasal congestion. Our experience demonstrates that RADA16 can be considered as a safe epistaxis treatment modality for HHT that is easy to apply and does not require the operating suite.

【摘要】成人遗传性出血性毛细血管扩张症（HHT）患者90%以上会发生鼻出血，可反复发作，发病率高。RADA16是一种自组装肽水凝胶，经美国食品和药物管理局批准用于止血和伤口愈合。在这项队列研究中，我们评估了鼻腔RADA16应用在控制hht相关鼻出血中的有效性。对一组接受鼻腔RADA16治疗且未改变其他治疗方法的成年患者进行回顾性图表回顾。收集鼻衄前后严重程度评分（ESS）、血红蛋白和红细胞压积来评估治疗效果。在纳入的患者（n = 22）中，有26例使用了RADA16。该队列中男性占54.5%，白人占86.4%，平均年龄为55.5岁，ACVRL1基因型占40.9%。基线平均ESS为5.0，在治疗后平均46.9天平均下降2.0，这是HHT中ESS最小临床重要差异（0.71）的2.8倍。平均基线血红蛋白（n = 13）和红细胞压积（n = 10）分别为11.3 g/dL和37.5%，应用RADA16后无显著变化。无出血、疼痛或过敏反应发生。几名患者报告轻度鼻塞。我们的经验表明，RADA16可以被认为是HHT的一种安全的鼻出血治疗方式，易于应用，不需要手术套件。

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引用次数: 0

The Bleeding Disorders Research Collaborative 出血性疾病研究合作组织

Blood Vessels, Thrombosis & Hemostasis

Pub Date : 2025-07-25 DOI: 10.1016/j.bvth.2025.100099

Leonard A. Valentino , Maria E. Santaella , Michelle L. Witkop , Raymond W. Stanhope , Sammie Valadez , Samantha A. Carlson , Halli Benasutti , Donna DiMichele , Michael Recht

Abstract

The Bleeding Disorders Research Collaborative (BDRC) aims to advance an accessible standard of care and quality of life for all people living with inheritable bleeding disorders. This goal will be achieved through collaborative and meaningful scientific inquiry, coordinated by an efficient research infrastructure, and undertaken by a diverse, capacitated workforce in partnership with an engaged community. The BDRC is supported by facilitative research policy and grounded in the principles of health equity, diversity, inclusion, accessibility, and belonging, striving for dignity, safety, well-being, and opportunities, leading to health justice. Importantly, the initiative is fully informed by lived experience experts, people affected by inheritable bleeding disorders, who are key members in the research development, implementation, and dissemination team.

出血性疾病研究协进会（BDRC）旨在为所有患有遗传性出血性疾病的人提供可获得的护理标准和生活质量。这一目标将通过协作和有意义的科学探究来实现，由高效的研究基础设施进行协调，并由多样化的、有能力的工作人员与参与其中的社区合作进行。BDRC得到促进性研究政策的支持，并以卫生公平、多样性、包容性、可及性和归属感原则为基础，争取尊严、安全、福祉和机会，从而实现卫生正义。重要的是，该倡议由生活经验专家提供充分信息，这些专家是受遗传性出血性疾病影响的人，他们是研究开发、实施和传播团队的关键成员。

引用次数: 0

Mitochondrial dysfunction–induced hemolysis: a precursor to vascular leakage and pulmonary hypertension 线粒体功能障碍引起的溶血：血管渗漏和肺动脉高压的前兆

Blood Vessels, Thrombosis & Hemostasis

Pub Date : 2025-07-25 DOI: 10.1016/j.bvth.2025.100097

Joel James ∗ , Maki Niihori ∗ , Mathews V. Varghese , Nolan McClain , Olga Rafikova , Ruslan Rafikov

引用次数: 0

M1 protein from group A Streptococcus affects fibrin clot formation, structure, and fibrinolytic potential 来自A群链球菌的M1蛋白影响纤维蛋白凝块的形成、结构和纤溶电位

Blood Vessels, Thrombosis & Hemostasis

Pub Date : 2025-07-18 DOI: 10.1016/j.bvth.2025.100094

Sophie Cherrington , Lewis J. Hardy , Azhar Maqbool , Helen Philippou , Craig Thelwell

Abstract

M1 protein is a major virulence determinant of group A Streptococcus (GAS). During infection, M1 is cleaved from the cell surface by host and bacterial proteases resulting in soluble M1 at the site of infection. M1 forms a supramolecular complex with host fibrinogen. We hypothesize that this supramolecular complex affects the formation of fibrin clots. Fibrin formation is an essential part of innate immunity, sealing off infections to limit bacteria spreading. The effects of recombinant M1 (rM1) were assessed in fibrin clots made from whole blood, plasma, or purified fibrinogen incubated in thrombin by a semiautomated coagulation analyzer, permeation studies, confocal microscopy, and scanning electron microscopy. Clotting and lysis profiles (with plasminogen activators and plasminogen) were investigated using microtiter plate assays and kinetically with rotational thromboelastography. Factor XIII crosslinking was quantified using commercial kits and sodium dodecyl sulfate–polyacrylamide gel electrophoresis densitometry analysis. This study demonstrated that rM1-bound (0.47-60 μg/mL) fibrinogen produced clots with remarkably different structures and properties compared with clots without rM1. Inclusion of rM1 formed heterogeneous clots with irregular fiber bundles and compacted fibrin. Formation of the protective fibrin film was disrupted by rM1. Furthermore, mechanical strength of fibrin clots was reduced, and the fibrin networks were more porous with increased fluid permeability. Fibrin clots formed using whole blood incorporating rM1 were more susceptible to lysis by plasmin. GAS strains of M1 type are often associated with invasive infections; the impact of M1 on fibrin structure could contribute to the severity of GAS infection by compromising the fibrin barrier that limits bacterial proliferation and migration.

摘要m1蛋白是a群链球菌（GAS）的主要毒力决定因子。在感染过程中，M1被宿主和细菌蛋白酶从细胞表面切割，在感染部位产生可溶性M1。M1与宿主纤维蛋白原形成超分子复合物。我们假设这种超分子复合物影响了纤维蛋白凝块的形成。纤维蛋白的形成是先天免疫的重要组成部分，它可以封闭感染，限制细菌的传播。重组M1 （rM1）的作用通过半自动化凝血分析仪、渗透研究、共聚焦显微镜和扫描电子显微镜，在由全血、血浆或纯化的纤维蛋白原在凝血酶中培养的纤维蛋白凝块中进行评估。凝血和溶解谱（与纤溶酶原激活剂和纤溶酶原）研究使用微量滴度板测定和动态旋转血栓弹性成像。采用商品化试剂盒和十二烷基硫酸钠-聚丙烯酰胺凝胶电泳密度分析法对因子十三交联进行定量分析。本研究表明，rM1结合（0.47-60 μg/mL）的纤维蛋白原产生的凝块与不含rM1的凝块相比，具有显著不同的结构和性质。rM1的包涵形成了不规则纤维束和致密纤维蛋白的异质凝块。保护性纤维蛋白膜的形成被rM1破坏。此外，纤维蛋白凝块的机械强度降低，纤维蛋白网络更多孔，流体渗透率增加。含rM1的全血形成的纤维蛋白凝块更容易被纤溶酶溶解。M1型GAS菌株常与侵袭性感染相关；M1对纤维蛋白结构的影响可能通过破坏限制细菌增殖和迁移的纤维蛋白屏障而导致GAS感染的严重程度。

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引用次数: 0

Endo-chip laser-induced thrombus formation: a vessel-on-chip model for in vitro testing of antithrombotic agents 芯片内激光诱导血栓形成：用于抗血栓药物体外测试的芯片上血管模型

Blood Vessels, Thrombosis & Hemostasis

Pub Date : 2025-07-18 DOI: 10.1016/j.bvth.2025.100096

Alexander Dupuy , Miao Qi , Jemma C. L. Fenwick , Daisie M. Yates , Paul R. Coleman , Jennifer R. Gamble , Lining Arnold Ju , Freda H. Passam

Abstract

Mouse models, such as the intravital laser-induced model of thrombus formation, are commonly used for mechanistic and preclinical studies in thrombosis. However, their translational value is limited by species differences. Few in vitro models incorporate laser-induced vascular injury. Here, we developed an endothelialized microfluidic device, the Endo-chip, to model thrombus formation in response to laser injury. Citrated blood was treated with IXA4, an endoplasmic reticulum stress inducer, or with antithrombotic agents including antitissue factor antibody (5G9), antiplatelet drugs (abciximab, aspirin), and anticoagulants (argatroban, heparin). Fluorescently labeled antibodies (to platelets, fibrin, or von Willebrand factor [VWF]), annexin V or the calcium dye Cal520, were added to the blood. After recalcification at 10 mM, blood was perfused through the Endo-chip at a shear rate of 100 s^–1 or 800 s^–1. Endothelial injury was induced with a 355-nm laser pulse producing a focal 10-μm injury, and phosphatidylserine exposure on endothelial cells within ∼1 cell diameter from the injury site. Annexin V-positive endothelial cells expressed tissue factor and released VWF, supporting localized platelet and fibrin deposition. The thrombus formed a teardrop morphology aligned with flow incorporating VWF with increasing shear. IXA4 enhanced platelet cytoplasmic calcium. Platelet accumulation was inhibited by abciximab but not aspirin, whereas coagulation inhibitors (5G9, argatroban, heparin) markedly reduced thrombus formation. These findings support that the Endo-chip laser-injury model incorporates key features of thrombus formation after endothelial injury, and provides a humanized, in vitro, alternative or auxiliary to mouse models for preclinical studies and antithrombotic drug development.

摘要小鼠模型，如活体激光诱导血栓形成模型，通常用于血栓形成的机制和临床前研究。然而，它们的翻译价值受到物种差异的限制。很少有体外模型包含激光诱导的血管损伤。在这里，我们开发了一种内皮化的微流体装置，endochip，来模拟激光损伤后血栓形成的反应。柠檬酸血用内质网应激诱导剂IXA4或抗血栓药物治疗，包括抗组织因子抗体（5G9）、抗血小板药物（阿昔单抗、阿司匹林）和抗凝剂（阿加曲班、肝素）。将荧光标记的抗体（针对血小板、纤维蛋白或血管性血液病因子[VWF]）、膜联蛋白V或钙染料Cal520加入血液中。在10 mM处再钙化后，血液以100 s-1或800 s-1的剪切速率通过endochip灌注。用355 nm激光脉冲诱导内皮细胞损伤，产生10 μm的病灶损伤，并将磷脂酰丝氨酸暴露在距损伤部位约1细胞直径的内皮细胞上。膜联蛋白v阳性内皮细胞表达组织因子并释放VWF，支持局部血小板和纤维蛋白沉积。血栓形成泪滴形态，与血流对齐，合并VWF，剪切增强。IXA4增强血小板胞质钙。阿昔单抗可抑制血小板积聚，但阿司匹林不能，而凝血抑制剂（5G9、阿加曲班、肝素）可显著减少血栓形成。这些发现支持endochip激光损伤模型包含内皮损伤后血栓形成的关键特征，并为临床前研究和抗血栓药物开发提供了一种人性化的、体外的、替代或辅助的小鼠模型。

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引用次数: 0

F9 missense variant hot spots associated with qualitative protein defects causing hemophilia B 与引起血友病B的定性蛋白缺陷相关的F9错义变异热点

Blood Vessels, Thrombosis & Hemostasis

Pub Date : 2025-07-18 DOI: 10.1016/j.bvth.2025.100095

Tirsa T. van Duijl , Samantha Gouw , Ina Kronevska , Alette Kooiker , Wil F. Kopatz , Nadia Freato , Marlene Beijlevelt , Henrike M. Hamer , Karin Fijnvandraat , Joost C. M. Meijers , Maartje van den Biggelaar

Abstract

Hemophilia B, a rare bleeding disorder, is caused by genetic variations in F9. Although quantitative factor IX (FIX) deficiencies are successfully treated by protein replacement therapy, qualitative defects may result in dysfunctional proteoforms in the circulation, potentially interfering with prophylactically or therapeutically administered recombinant FIX (rFIX) concentrates. To delineate the F9 missense variants associated with qualitative defects, we integrated genotype and phenotype from the European Association for Haemophilia and Allied Disorders F9 Coagulation Factor Variant Database. Of the 663 patients for whom activity (FIX:Act) and antigen (FIX:Ag) data were available, 40% of patients with severe hemophilia (n = 248), 50% of patients with moderate hemophilia (n = 244), and 47% of patients with mild hemophilia (n = 171) had cross-reactive material defined as FIX:Ag ≥40%. Variants associated with qualitative defects were predominantly localized (1) at proteolytic sites for FIX processing and activation, (2) within exosite II of the serine protease domain, and (3) at calcium ion coordinating residues within the Gla/EGF-1 domain of the FIX light chain. To study the effect of dysfunctional FIX proteoforms on thrombin generation in the presence of rFIX, we investigated 2 individuals with hemophilia B harboring a variant of unknown significance with an unexplained bleeding phenotype despite prophylaxis. Ex vivo therapeutic monitoring using patient plasma supplemented with rFIX concentrates, bypassing agent or emicizumab, enabled head-to-head comparison and revealed limited normalization of the prolonged initiation phase in coagulation. Alignment of information on genotype with functional proteotype may clarify the heterogeneity in bleeding phenotype and treatment response and provide a stepping stone for personalized care.

嗜血友病B是一种罕见的出血性疾病，由F9基因变异引起。虽然定量因子IX （FIX）缺乏可以通过蛋白质替代疗法成功治疗，但定性缺陷可能导致循环中功能失调的蛋白形式，潜在地干扰预防性或治疗性给予的重组FIX （rFIX）浓缩物。为了描述与质量缺陷相关的F9错义变异，我们整合了来自欧洲血友病和相关疾病协会F9凝血因子变异数据库的基因型和表型。在可获得活性（FIX:Act）和抗原（FIX:Ag）数据的663例患者中，40%的严重血友病患者（n = 248）， 50%的中度血友病患者（n = 244）和47%的轻度血友病患者（n = 171）具有交叉反应物质，定义为FIX:Ag≥40%。与质量缺陷相关的变异主要定位于(1)FIX加工和激活的蛋白水解位点，(2)丝氨酸蛋白酶结构域的外源位点II，以及(3)FIX轻链Gla/EGF-1结构域的钙离子配位残基。为了研究功能失调的FIX蛋白形态在rFIX存在下对凝血酶生成的影响，我们调查了2例血友病B患者，他们携带一种未知意义的变异，尽管进行了预防，但仍存在不明原因的出血表型。体外治疗监测使用患者血浆补充rFIX浓缩物、旁路药或emicizumab，实现了头对头比较，并显示凝血起始期延长的有限正常化。将基因型信息与功能蛋白型信息进行比对，可以澄清出血表型和治疗反应的异质性，并为个性化护理提供基础。

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引用次数: 0

Platelet reactivity expression score in diabetes mellitus 糖尿病患者血小板反应性表达评分

Blood Vessels, Thrombosis & Hemostasis

Pub Date : 2025-07-05 DOI: 10.1016/j.bvth.2025.100092

Carine E. Hamo , Matthew A. Muller , Jonathan D. Newman , Joshua Beckman , Kelly V. Ruggles , Tessa J. Barrett , Jeffrey S. Berger

引用次数: 0

A novel in vitro model of trauma-induced endotheliopathy provides a platform for studying mechanisms of coagulopathy 一种新的体外创伤性内皮病变模型为研究凝血功能障碍的机制提供了一个平台

Blood Vessels, Thrombosis & Hemostasis

Pub Date : 2025-07-05 DOI: 10.1016/j.bvth.2025.100087

Jeries Abu-Hanna , Gang Xu , Gael B. Morrow , Lewis Timms , Naveed Akbar , Mike Laffan , Robin P. Choudhury , Nicola Curry

Abstract

Trauma-induced coagulopathy (TIC) significantly contributes to trauma-related mortality, driven by dysregulated coagulation and fibrinolysis. Endotheliopathy of trauma (EoT) is central to TIC, yet its underlying mechanisms remain unclear. Current in vitro models fail to replicate the complex trauma environment, including hemorrhagic shock, tissue injury, and inflammation. This study aimed to develop a novel in vitro model of EoT that mimics key TIC features, enabling the investigation of endothelial contributions to TIC. Endothelial colony-forming cells (ECFCs) were exposed to trauma-relevant factors, including epinephrine, tumor necrosis factor α, interleukin 6, high mobility group box 1, hydrogen peroxide, and hypoxia. Endothelial injury markers (syndecan-1 and thrombomodulin), hemostatic protein expression, coagulation, and fibrinolysis were analyzed using enzyme-linked immunosorbent assay, immunofluorescence, global hemostasis assays, and RNA sequencing. Plasma from healthy donors and trauma patients was used to assess clinical relevance. Traumatized ECFCs exhibited progressive dysfunction, with early surface damage and sustained fibrinolytic dysregulation. Transcriptomic analysis showed activation of inflammatory pathways, metabolic shifts, and epigenetic changes. Surface expression of anticoagulant proteins decreased, whereas procoagulant tissue factor increased, heightening thrombogenic potential. Initially, traumatized ECFCs promoted fibrinolysis via thrombomodulin shedding but later secreted antifibrinolytic plasminogen activator inhibitor 1, mimicking the biphasic TIC phenotype. Plasma assays revealed thrombin generation and clot lysis changes similar to trauma patients. This in vitro model successfully replicates EoT and TIC-associated hemostatic imbalances, capturing the time-dependent evolution of endothelial dysfunction. It provides mechanistic insights into TIC and serves as a platform for testing targeted interventions to mitigate endothelial-driven coagulopathy in trauma.

摘要创伤性凝血功能障碍（TIC）是由凝血和纤溶异常引起的创伤性死亡率的重要因素。创伤性内皮病变（EoT）是TIC的核心，但其潜在机制尚不清楚。目前的体外模型无法复制复杂的创伤环境，包括失血性休克、组织损伤和炎症。本研究旨在建立一种新的体外EoT模型，模拟TIC的关键特征，从而研究内皮细胞对TIC的贡献。内皮集落形成细胞（ECFCs）暴露于创伤相关因素，包括肾上腺素、肿瘤坏死因子α、白细胞介素6、高迁移率组盒1、过氧化氢和缺氧。内皮损伤标志物（syndecan-1和血栓调节蛋白）、止血蛋白表达、凝血和纤维蛋白溶解均采用酶联免疫吸附法、免疫荧光法、整体止血法和RNA测序进行分析。来自健康供体和创伤患者的血浆用于评估临床相关性。创伤后的ecfc表现出进行性功能障碍，早期表面损伤和持续的纤维蛋白溶解失调。转录组学分析显示炎症通路激活、代谢变化和表观遗传变化。抗凝蛋白的表面表达减少，而促凝组织因子增加，提高了血栓形成的潜力。最初，创伤后的ecfc通过血栓调节蛋白脱落促进纤维蛋白溶解，但后来分泌抗纤溶酶原激活物抑制剂1，模拟双期TIC表型。血浆检测显示凝血酶生成和凝块溶解变化与创伤患者相似。该体外模型成功复制了EoT和tic相关的止血失衡，捕捉了内皮功能障碍的时间依赖性演变。它提供了TIC的机制见解，并作为测试靶向干预措施以减轻创伤中内皮驱动的凝血功能障碍的平台。

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引用次数: 0

M protein and the evolving spectrum of platelet-activating anti-PF4 disorders and MGTS and their linkage M蛋白与血小板活化抗pf4疾病和MGTS及其关联的演变谱

Blood Vessels, Thrombosis & Hemostasis

Pub Date : 2025-07-05 DOI: 10.1016/j.bvth.2025.100093

Tajamul H. Mir , Rushad Patell , Jason A. Freed

引用次数: 0