Research and Practice in Thrombosis and Haemostasis最新文献

英文中文

Loss of endogenous Nox2-NADPH oxidase does not prevent age-induced platelet activation and arterial thrombosis in mice 内源性 Nox2-NADPH 氧化酶的缺失并不能防止小鼠因年龄增长而引起的血小板活化和动脉血栓形成

IF 3.4 3区医学 Q2 HEMATOLOGY

Research and Practice in Thrombosis and Haemostasis

Pub Date : 2024-10-01 DOI: 10.1016/j.rpth.2024.102597

Azaj Ahmed , Gokul Patil , Vijay K. Sonkar , Melissa Jensen , Jennifer Streeter , Sanjana Dayal

Background

Reactive oxygen species are known to contribute to platelet hyperactivation and thrombosis during aging; however, the mechanistic contribution of the specific oxidative pathway remains elusive.

Objectives

We hypothesized that during aging, endogenous Nox2-NADPH oxidase contributes to platelet reactive oxygen species accumulation and that loss of Nox2 will protect from platelet activation and thrombosis.

Methods

We studied littermates of Nox2 knockout (Nox2-KO) and -wild-type (Nox2-WT) mice at young (3-4 months) and old (18-20 months) age. Within platelets, we examined the expression of subunits of NADPH oxidase and enzyme activity, oxidant levels, activation markers, aggregation, and secretion. We also assessed susceptibility to in vivo thrombosis in 2 experimental models.

Results

While aged Nox2-WT mice displayed increased mRNA levels for Nox2, aged Nox2-KO mice showed an increase in Nox4 mRNA. However, neither the protein levels of several subunits nor the activity of NADPH oxidase were found to be altered by age or genotype. Both aged Nox2-WT and aged Nox2-KO mice exhibited similar enhancement in levels of platelet oxidants, granule release, α_IIbβ₃ activation, annexin V binding, aggregation and secretion, and a greater susceptibility to platelet-induced pulmonary thrombosis compared with young mice. In a photochemical injury model, adoptive transfer of platelets from aged Nox2-WT or Nox2-KO mice to the aged host mice resulted in a similar time to develop occlusive thrombus in the carotid artery. These findings suggest that loss of endogenous Nox2 does not protect against age-related platelet activation and arterial thrombosis in mice.

Conclusion

We conclude that Nox2 is not an essential mediator of prothrombotic effects associated with aging.

背景众所周知，活性氧是衰老过程中血小板过度激活和血栓形成的原因之一；然而，特定氧化途径的机理作用仍然难以确定。方法我们研究了幼年（3-4 个月）和老年（18-20 个月）Nox2 基因敲除（Nox2-KO）小鼠和野生型（Nox2-WT）小鼠的同窝小鼠。在血小板内，我们检测了 NADPH 氧化酶亚基的表达和酶活性、氧化剂水平、活化标记物、聚集和分泌。我们还在两个实验模型中评估了体内血栓形成的易感性。结果虽然老龄 Nox2-WT 小鼠的 Nox2 mRNA 水平升高，但老龄 Nox2-KO 小鼠的 Nox4 mRNA 水平升高。然而，几个亚基的蛋白质水平和 NADPH 氧化酶的活性都没有因年龄或基因型而发生变化。与年轻小鼠相比，年老的 Nox2-WT 小鼠和年老的 Nox2-KO 小鼠在血小板氧化剂水平、颗粒释放、αⅡbβ3 激活、附件素 V 结合、聚集和分泌方面都表现出相似的增强，而且更容易发生血小板诱导的肺血栓形成。在光化学损伤模型中，将老龄 Nox2-WT 或 Nox2-KO 小鼠的血小板收养转移到老龄宿主小鼠体内，颈动脉形成闭塞性血栓的时间相似。这些研究结果表明，内源性 Nox2 的缺失并不能保护小鼠免受与年龄相关的血小板活化和动脉血栓形成的影响。

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引用次数: 0

Comorbidity and adverse events in acquired hemophilia A: data from the GTH-AHA-EMI study 获得性血友病 A 的合并症和不良事件：来自 GTH-AHA-EMI 研究的数据

IF 3.4 3区医学 Q2 HEMATOLOGY

Research and Practice in Thrombosis and Haemostasis

Pub Date : 2024-10-01 DOI: 10.1016/j.rpth.2024.102565

Christian Herbert Burgmann , Ulrich J. Sachs , Karolin Trautmann-Grill , Christian Pfrepper , Paul Knöbl , Richard Greil , Johannes Oldenburg , Wolfgang Miesbach , Katharina Holstein , Hermann Eichler , Patrick Möhnle , Matthias Höpting , Christiane Dobbelstein , Robert Klamroth , Andreas Tiede

Background

Persons with acquired hemophilia A are often older and suffer from comorbidity or frailty. Little is known about the impact on clinically relevant outcomes of acquired hemophilia A.

Objectives

To assess the relevance of age, physical performance status, comorbidity, and concomitant medication on the risk of bleeding and other outcomes.

Methods

Post hoc analysis of data from the GTH-AHA-EMI study that used emicizumab for bleed protection and withheld immunosuppressive treatment during the early phase of management. Primary endpoint was the rate of clinically relevant new bleeding (CRNB) during the first 12 weeks of emicizumab prophylaxis.

Results

Forty-seven patients were enrolled. Median age was 76 years; performance status (World Health Organization performance status [WHO-PS]) was 3 or worse in 41%; Charlson comorbidity index (CCI) was 5 or higher in 63%; antithrombotic drugs were reported in 34%. Rate of CRNB during 12 weeks of emicizumab prophylaxis was similar across subgroups of age, sex, WHO-PS, CCI, baseline factor VIII activity, and inhibitor titer. Patients with CRNB during the study had more severe anemia already at baseline. However, persistent severe anemia in week 4 was not related to risk of bleeding beyond this time. CRNB was associated with injury from falling in 7 of 14 patients. Adverse events grade 3 or higher were not related to baseline CCI or age but were more frequent in patients with poor WHO-PS.

Conclusion

Emicizumab provided bleed protection regardless of age and comorbidity. Clinical baseline characteristics did not predict breakthrough bleeding under emicizumab. Poor WHO-PS at baseline was associated with severe adverse events during the study.

背景后天性甲型血友病患者通常年龄较大，患有合并症或身体虚弱。方法对 GTH-AHA-EMI 研究的数据进行事后分析，该研究使用埃米珠单抗保护出血，并在早期管理阶段暂停免疫抑制治疗。主要终点是埃米珠单抗预防性治疗头12周内临床相关新出血率（CRNB）。中位年龄为76岁；41%的患者表现状态（世界卫生组织表现状态[WHO-PS]）为3级或更差；63%的患者夏尔森合并症指数（CCI）为5级或更高；34%的患者报告服用了抗血栓药物。不同年龄、性别、WHO-PS、CCI、基线因子 VIII 活性和抑制剂滴度的亚组在埃米珠单抗预防治疗 12 周期间的 CRNB 发生率相似。在研究期间出现 CRNB 的患者在基线时已经出现了较严重的贫血。然而，第 4 周的持续严重贫血与此后的出血风险无关。14 名患者中有 7 名患者的 CRNB 与摔伤有关。3级或更高的不良事件与基线CCI或年龄无关，但在WHO-PS较差的患者中更为常见。临床基线特征并不能预测埃米珠单抗的突破性出血。基线WHO-PS较差与研究期间的严重不良事件有关。

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引用次数: 0

Thrombin generation to evaluate the complex hemostatic balance of hemophilia A plasma containing direct oral anticoagulant and supplemented by factor VIII 生成凝血酶以评估含有直接口服抗凝剂和补充因子 VIII 的 A 型血友病血浆的复杂止血平衡情况

IF 3.4 3区医学 Q2 HEMATOLOGY

Research and Practice in Thrombosis and Haemostasis

Pub Date : 2024-10-01 DOI: 10.1016/j.rpth.2024.102576

Sylvain Lamoine , Vincent Jury , Virginie Fourneyron , Jonathan Douxfils , Dorian Teissandier , Laurie Talon , Thomas Sinegre , Aurélien Lebreton

Background

The incidence of cardiovascular diseases is increasing in persons with hemophilia A (HA). Therefore, anticoagulant therapy based on direct oral anticoagulants (DOACs) may be needed, despite the bleeding risk. In case of surgery or bleeding, such patients may be concomitantly treated with emicizumab (routine prophylaxis), factor (F)VIII products, and DOAC. Their concomitant presence constitutes a hemostatic challenge. Recent international guidelines stated that data are scarce on the hemostatic balance of plasma samples from patients with HA receiving emicizumab and DOAC.

Objectives

The aim of this observational study was to assess the coagulation of FVIII-deficient plasma spiked with DOAC and emicizumab and to evaluate the effects of FVIII addition.

Methods

Prothrombin time, activated partial thromboplastin time, and thrombin generation (TG) using the calibrated automated thrombogram method were evaluated in aliquots of a commercial severe HA plasma supplemented with emicizumab (0, 12.5, 25, 50, and 100 ng/mL), DOAC (0, 50, 100, 200, and 400 ng/mL of apixaban, rivaroxaban, edoxaban, or dabigatran) and FVIII (0%, 5%, 15%, 50%, and 100%).

Results

DOAC rapidly induced a TG decrease. Emicizumab could counter this effect only for the lowest DOAC dose. FVIII addition to the FVIII-deficient plasma containing a DOAC and emicizumab improved TG and countered the anticoagulant effect of DOAC at ≤100 ng/mL.

Conclusion

Our findings indicate that FVIII can be safely used with emicizumab to counter the anticoagulant effect of DOAC at ≤100 ng/mL. The TG assay is an efficient tool to monitor plasma containing anti-FXa DOAC, but not dabigatran (anti-FIIa).

背景A型血友病（HA）患者的心血管疾病发病率正在上升。因此，尽管存在出血风险，但仍可能需要使用直接口服抗凝剂（DOACs）进行抗凝治疗。在手术或出血的情况下，这类患者可同时使用埃米珠单抗（常规预防）、因子（F）VIII 产品和 DOAC。它们的同时存在构成了止血挑战。本观察性研究旨在评估添加了 DOAC 和埃米珠单抗的 FVIII 缺乏血浆的凝血情况，并评估添加 FVIII 的效果。方法使用校准自动血栓图法评估了添加了埃米珠单抗（0、12、25、50 和 100）的商用重症 HA 血浆的凝血酶原时间、活化部分凝血活酶时间和凝血酶生成量（TG）。5、25、50 和 100 纳克/毫升）、DOAC（0、50、100、200 和 400 纳克/毫升的阿哌沙班、利伐沙班、依多沙班或达比加群）和 FVIII（0%、5%、15%、50% 和 100%）。只有在 DOAC 剂量最低时，Emicizumab 才能抵消这种效应。结论我们的研究结果表明，在≤100 ng/mL时，FVIII可安全地与埃米珠单抗一起用于对抗DOAC的抗凝作用。TG测定是监测血浆中含有抗FXa DOAC而非达比加群（抗FIIa）的有效工具。

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引用次数: 0

Distinguishing hyperfibrinolysis from enhanced–fibrinolytic-type disseminated intravascular coagulation 区分纤溶亢进与纤溶增强型弥散性血管内凝血

IF 3.4 3区医学 Q2 HEMATOLOGY

Research and Practice in Thrombosis and Haemostasis

Pub Date : 2024-10-01 DOI: 10.1016/j.rpth.2024.102574

Shinya Yamada, Toshihiro Miyamoto, Hidesaku Asakura

引用次数: 0

Hospital-acquired venous thromboembolism among critically ill children with diabetic ketoacidosis: a multicenter, retrospective cohort study 糖尿病酮症酸中毒危重患儿在医院获得性静脉血栓栓塞症：一项多中心回顾性队列研究

IF 3.4 3区医学 Q2 HEMATOLOGY

Research and Practice in Thrombosis and Haemostasis

Pub Date : 2024-10-01 DOI: 10.1016/j.rpth.2024.102581

Kristin M. DeMayo , Elizabeth E. Havlicek , Marisol Betensky , Neil A. Goldenberg , Anthony A. Sochet

Background

Critically ill children and young adults with diabetic ketoacidosis are thought to be in a prothrombotic state. However, the rate of hospital-acquired venous thromboembolism and associated risk factors in this population have not been identified.

Objectives

Children hospitalized for diabetic ketoacidosis (DKA) may be at increased risk of hospital-acquired venous thromboembolism (HA-VTE). We sought to estimate the incidence of HA-VTE and identify unique prothrombotic risk factors in this population.

Methods

We performed a multicenter, retrospective cohort study using the Pediatric Health Information Systems registry including patients aged 0 to 21 years hospitalized for DKA from January 2017 to December 2023 within 48 participating centers. The primary outcome was the frequency of HA-VTE. Secondary outcomes were rates of cerebral edema, central venous catheterization (CVC), invasive mechanical ventilation (IMV), infection, and length of stay (LOS). An adjusted logistic regression was employed to identify potential HA-VTE risk factors.

Results

Of the 27,613 patients studied, 93 (0.3%) developed a HA-VTE. Compared with those without HA-VTE, those with HA-VTE had a greater median LOS (10 [IQR, 5-21] vs 2 [IQR, 2-3] days) and rates of cerebral edema (25.8% vs 6.6%), CVC (23.7% vs 1.1%), infection (72% vs 23.5%), and IMV (39.8% vs 1.4%; all P < .001). In an adjusted logistic model, factors independently associated with increased HA-VTE were CVC (adjusted odds ratio [aOR], 3.04; 95% CI, 1.49-6.19), infection (aOR, 4.61; 95% CI, 2.81-7.56), IMV (aOR, 9.24; 95% CI, 4.83-17.56), and increasing LOS (aOR, 1.05; 95% CI, 1.02-1.06; all P < .01).

Conclusion

The frequency of HA-VTE among critically ill children and young adults hospitalized for DKA was 0.3%. After prospective validation, putative risk factors (ie, CVC, IMV, infection, and extended LOS) may be incorporated into the design of forthcoming pediatric thromboprophylaxis trials.

背景患有糖尿病酮症酸中毒的重症儿童和年轻成人被认为处于血栓形成前状态。目标因糖尿病酮症酸中毒（DKA）住院的儿童发生医院获得性静脉血栓栓塞症（HA-VTE）的风险可能增加。我们试图估算 HA-VTE 的发生率，并确定这一人群中独特的血栓形成前风险因素。方法我们利用儿科健康信息系统登记册开展了一项多中心、回顾性队列研究，研究对象包括 2017 年 1 月至 2023 年 12 月期间在 48 个参与中心因 DKA 住院的 0 至 21 岁患者。主要结果是 HA-VTE 的发生频率。次要结果是脑水肿、中心静脉导管插入术（CVC）、有创机械通气（IMV）、感染和住院时间（LOS）的发生率。结果在接受研究的27613名患者中，93人（0.3%）发生了HA-VTE。与未发生 HA-VTE 的患者相比，发生 HA-VTE 的患者的中位住院日（10 [IQR, 5-21] 天 vs 2 [IQR, 2-3] 天）和脑水肿率（25.8% vs 6.6%）、CVC（23.7% vs 1.1%）、感染（72% vs 23.5%）和 IMV（39.8% vs 1.4%；所有 P 均为 0.001）更高。在调整后的逻辑模型中，与 HA-VTE 增加独立相关的因素有 CVC（调整后的几率比 [aOR]，3.04；95% CI，1.49-6.19）、感染（aOR，4.61；95% CI，2.81-7.56）、IMV（aOR，9.24; 95% CI, 4.83-17.56), and increasing LOS (aOR, 1.05; 95% CI, 1.02-1.06; all P < .01).经过前瞻性验证后，推测的风险因素（即CVC、IMV、感染和延长的LOS）可纳入即将开展的儿科血栓预防试验的设计中。

{"title":"Hospital-acquired venous thromboembolism among critically ill children with diabetic ketoacidosis: a multicenter, retrospective cohort study","authors":"Kristin M. DeMayo , Elizabeth E. Havlicek , Marisol Betensky , Neil A. Goldenberg , Anthony A. Sochet","doi":"10.1016/j.rpth.2024.102581","DOIUrl":"10.1016/j.rpth.2024.102581","url":null,"abstract":"<div><h3>Background</h3><div>Critically ill children and young adults with diabetic ketoacidosis are thought to be in a prothrombotic state. However, the rate of hospital-acquired venous thromboembolism and associated risk factors in this population have not been identified.</div></div><div><h3>Objectives</h3><div>Children hospitalized for diabetic ketoacidosis (DKA) may be at increased risk of hospital-acquired venous thromboembolism (HA-VTE). We sought to estimate the incidence of HA-VTE and identify unique prothrombotic risk factors in this population.</div></div><div><h3>Methods</h3><div>We performed a multicenter, retrospective cohort study using the Pediatric Health Information Systems registry including patients aged 0 to 21 years hospitalized for DKA from January 2017 to December 2023 within 48 participating centers. The primary outcome was the frequency of HA-VTE. Secondary outcomes were rates of cerebral edema, central venous catheterization (CVC), invasive mechanical ventilation (IMV), infection, and length of stay (LOS). An adjusted logistic regression was employed to identify potential HA-VTE risk factors.</div></div><div><h3>Results</h3><div>Of the 27,613 patients studied, 93 (0.3%) developed a HA-VTE. Compared with those without HA-VTE, those with HA-VTE had a greater median LOS (10 [IQR, 5-21] vs 2 [IQR, 2-3] days) and rates of cerebral edema (25.8% vs 6.6%), CVC (23.7% vs 1.1%), infection (72% vs 23.5%), and IMV (39.8% vs 1.4%; all <em>P</em> < .001). In an adjusted logistic model, factors independently associated with increased HA-VTE were CVC (adjusted odds ratio [aOR], 3.04; 95% CI, 1.49-6.19), infection (aOR, 4.61; 95% CI, 2.81-7.56), IMV (aOR, 9.24; 95% CI, 4.83-17.56), and increasing LOS (aOR, 1.05; 95% CI, 1.02-1.06; all <em>P</em> < .01).</div></div><div><h3>Conclusion</h3><div>The frequency of HA-VTE among critically ill children and young adults hospitalized for DKA was 0.3%. After prospective validation, putative risk factors (ie, CVC, IMV, infection, and extended LOS) may be incorporated into the design of forthcoming pediatric thromboprophylaxis trials.</div></div>","PeriodicalId":20893,"journal":{"name":"Research and Practice in Thrombosis and Haemostasis","volume":"8 7","pages":"Article 102581"},"PeriodicalIF":3.4,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142571818","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Evaluation of hemostasis understanding in medical and pharmacy students from a Parisian university 评估巴黎一所大学医学和药学专业学生对止血知识的了解程度

IF 3.4 3区医学 Q2 HEMATOLOGY

Research and Practice in Thrombosis and Haemostasis

Pub Date : 2024-08-01 DOI: 10.1016/j.rpth.2024.102547

Nicolas Gendron , Dominique Helley , Philippe Rousselot , Virginie Siguret , Pascale Gaussem , Chloé James , Lina Khider , Nadine Ajzenberg , Elodie Boissier , Nicolas Boissel , David M. Smadja , Benjamin Planquette

引用次数: 0

Poster Abstracts 海报摘要

IF 3.4 3区医学 Q2 HEMATOLOGY

Research and Practice in Thrombosis and Haemostasis

Pub Date : 2024-08-01 DOI: 10.1016/j.rpth.2024.102504

引用次数: 0

Is lupus anticoagulant testing with dilute Russell’s viper venom clotting times reliable in the presence of inflammation? 在有炎症的情况下，用稀释的罗素蝰蛇毒凝血时间进行狼疮抗凝检测可靠吗？

IF 3.4 3区医学 Q2 HEMATOLOGY

Research and Practice in Thrombosis and Haemostasis

Pub Date : 2024-08-01 DOI: 10.1016/j.rpth.2024.102536

Michael Hardy , Emilie Catry , Marie Pouplard , Thomas Lecompte , François Mullier

Background

Testing for lupus anticoagulant (LA) is not recommended in case of inflammation as C-reactive protein (CRP) can interfere in vitro with the phospholipids present in the activated partial thromboplastin time test used to detect an LA. However, the potential interference of an acute phase protein (ie, CRP) in LA testing using the dilute Russell’s viper venom (DRVV) test is poorly studied.

Objectives

To study the effect of inflammation, as evidenced by increased CRP levels, on DRVV tests.

Methods

First, a retrospective analysis (2013-2023) was performed: data on all LA workups were retrieved, and the association between CRP levels and DRVV screen, mix, and confirm clotting times was studied. Second, data on DRVV panels and CRP levels were extracted from 2 prospective studies involving intensive care unit patients to study the association between both variables. Third, CRP was added to normal pooled plasma at 6 relevant concentrations (up to 416 mg/L) to study the association between CRP itself and DRVV coagulation times.

Results

In the retrospective analysis, DRVV screen and confirm clotting times significantly increased as CRP increased (increase of 0.11 seconds and 0.03 seconds per 1 mg/L increase of CRP level, respectively). In the prospective analysis, only DRVV screen was prolonged with high CRP levels (increase of 0.06 seconds for a 1 mg/L increase in CRP level); DRVV screen/confirm ratio was also increased with high CRP levels. In vitro, the addition of CRP did not significantly increase any DRVV clotting times.

Conclusion

LA testing should be performed with much caution in the presence of inflammation as it may be associated with prolongation of both activated partial thromboplastin time and DRVV clotting times.

背景由于C反应蛋白（CRP）会在体外干扰用于检测狼疮抗凝物（LA）的活化部分凝血活酶时间试验中的磷脂，因此在有炎症的情况下不建议检测狼疮抗凝物（LA）。方法首先，进行回顾性分析（2013-2023 年）：检索所有 LA 检查数据，研究 CRP 水平与 DRVV 筛查、混合和确认凝血时间之间的关联。其次，从两项涉及重症监护室患者的前瞻性研究中提取 DRVV 面板和 CRP 水平的数据，研究这两个变量之间的关联。结果在回顾性分析中，随着 CRP 的增加，DRVV 筛选和确认凝血时间显著增加（CRP 水平每增加 1 毫克/升，分别增加 0.11 秒和 0.03 秒）。在前瞻性分析中，只有 DRVV 筛选时间随 CRP 水平升高而延长（CRP 水平每升高 1 毫克/升，延长时间为 0.06 秒）；DRVV 筛选/确认比率也随 CRP 水平升高而增加。在体外，CRP 的添加并不会明显增加 DRVV 的凝血时间。结论在有炎症的情况下，LA 检测应非常谨慎，因为它可能与活化部分凝血活酶时间和 DRVV 凝血时间的延长有关。

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引用次数: 0

Plant-derived compounds normalize platelet bioenergetics and function in hyperglycemia 植物萃取化合物可使高血糖状态下的血小板生物能和功能恢复正常

IF 3.4 3区医学 Q2 HEMATOLOGY

Research and Practice in Thrombosis and Haemostasis

Pub Date : 2024-08-01 DOI: 10.1016/j.rpth.2024.102548

Julia S. Gauer , Abigail Ajanel , Lutale M. Kaselampao , Isabel Candir , Amanda D.V. MacCannell , Lee D. Roberts , Robert A. Campbell , Robert A.S. Ariëns

Background

Polyphenols have been shown to decrease oxidative stress and modulate glycemic response. Nevertheless, their effect on platelet bioenergetics and clot structure in diabetes and hyperglycemia is unknown.

Objectives

To investigate the effect of polyphenols on human platelet bioenergetics and its subsequent effect on clot structure in normoglycemia vs acute hyperglycemia in vitro.

Methods

Four polyphenols (resveratrol, hesperetin, epigallocatechin gallate [EGCG], and quercetin) were selected for initial analysis. Healthy volunteers’ isolated platelets/platelet-rich plasma were treated with 5 or 25 mM glucose to represent normoglycemia and acute hyperglycemia, respectively. Platelet-derived reactive oxygen species (ROS), citrate synthase activity (mitochondrial density), mitochondrial calcium flux, and mitochondrial respiration were performed following exposure to polyphenols (20 µM, 1 hour) to determine their effects on platelet bioenergetics. Procoagulant platelets (annexin V) and fibrin fiber density (Alexa Fluor-488 fibrinogen; Invitrogen) were analyzed by laser scanning confocal microscopy, while clot porosity was determined using platelet-rich plasma following exposure to polyphenols (20 µM, 20 minutes).

Results

Acute hyperglycemia increased ROS, mitochondrial calcium flux, maximal respiration, and procoagulant platelet number. Resveratrol, quercetin, and EGCG reduced platelet ROS in normoglycemic and acute hyperglycemic conditions. Mitochondrial density was decreased by quercetin and EGCG in normoglycemia. Resveratrol and EGCG reduced mitochondrial calcium flux in acute hyperglycemia. Resveratrol also decreased procoagulant platelet number and attenuated oxygen consumption rate in normoglycemia and acute hyperglycemia. No effect of hyperglycemia or polyphenols was observed on fibrin fiber density or clot pore size.

Conclusion

Our results suggest polyphenols attenuate increased platelet activity stemming from hyperglycemia and may benefit thrombosis-preventative strategies in patients with diabetes.

背景多酚已被证明可以降低氧化应激和调节血糖反应。目的研究多酚对正常血糖与急性高血糖体外实验中人体血小板生物能的影响及其对血栓结构的影响。方法选择四种多酚（白藜芦醇、橙皮甙、没食子酸表没食子儿茶素 [EGCG] 和槲皮素）进行初步分析。健康志愿者的分离血小板/富含血小板的血浆分别用 5 或 25 mM 葡萄糖处理，以代表正常血糖和急性高血糖。在接触多酚（20 µM，1 小时）后，对血小板源性活性氧（ROS）、柠檬酸合成酶活性（线粒体密度）、线粒体钙通量和线粒体呼吸进行检测，以确定它们对血小板生物能的影响。通过激光扫描共聚焦显微镜分析了促凝血小板（annexin V）和纤维蛋白纤维密度（Alexa Fluor-488 纤维蛋白原；Invitrogen 公司），同时在接触多酚（20 µM，20 分钟）后使用富血小板血浆测定了血块孔隙率。白藜芦醇、槲皮素和 EGCG 可减少正常血糖和急性高血糖条件下的血小板 ROS。在正常血糖情况下，槲皮素和 EGCG 可降低线粒体密度。白藜芦醇和 EGCG 可降低急性高血糖时线粒体的钙通量。在正常血糖和急性高血糖情况下，白藜芦醇还能减少促凝血血小板的数量并降低耗氧量。结论：我们的研究结果表明，多酚可以减轻因高血糖引起的血小板活性增加，并可能有利于糖尿病患者的血栓预防策略。

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引用次数: 0

Erratum to ‘Performance of Risk Scores in Predicting Major Bleeding in Left Ventricular Assist Device (LVAD) Recipients: a Comparative External Validation. ’[Res Pract Thromb Haemost. 2024;8:e102437] 风险评分在预测左心室辅助装置（LVAD）受术者大出血中的表现：一项外部比较验证》的勘误。'[Res Pract Thromb Haemost.］

IF 3.4 3区医学 Q2 HEMATOLOGY

Research and Practice in Thrombosis and Haemostasis

Pub Date : 2024-08-01 DOI: 10.1016/j.rpth.2024.102558

S.F.B. van der Horst , Y. de Jong , N. van Rein , J.W. Jukema , M. Palmen , E. Janssen , E.F. Bonneville , F.A. Klok , M.V. Huisman , L.F. Tops , P.L. den Exter

引用次数: 0

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