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心脏手术中具有血小板反应蛋白基序的解聚素和金属蛋白酶13(ADAMTS13)活性的围手术期分析:动力学和机制洞察

Perioperative Profiling of a Disintegrin and Metalloprotease with Thrombospondin Type 1 Motif, Member 13 (ADAMTS13) Activity in Cardiac Surgery: Kinetics and Mechanistic Insights.

作者信息

Strasser Bernhard, Knotzer Johann, Sartori Selina, Poidinger Bernhard, Kotzinger Oskar, Irsara Christian, Lirk Gerald, Gunz Carolin, Haushofer Alexander

机构信息

Institute of Clinical Chemistry and Laboratory Medicine, Klinikum Wels-Grieskirchen, 4600 Wels, Austria.

Department of Anaesthesiology and Critical Care, Klinikum Wels-Grieskirchen, 4600 Wels, Austria.

出版信息

J Clin Med. 2025 Jul 11;14(14):4936. doi: 10.3390/jcm14144936.

DOI:10.3390/jcm14144936
PMID:40725629
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC12295668/
Abstract

The enzyme A Disintegrin and metalloprotease with thrombospondin type 1 motif, member 13 (ADAMTS13) regulates hemostasis by cleaving von Willebrand factor (VWF) multimers. ADAMTS13-VWF axis dysregulation leads to different thrombotic conditions. This study investigated changes in ADAMTS13 activity during major cardiac procedures and their relationship to VWF changes and clinical complications. A total of 628 ADAMTS13 activity and inhibitor measurements were carried out in 168 patients who underwent cardiac surgery. ADAMTS13 activity was measured after the initiation of anesthesia and daily for up to 6 days postoperatively via Technozym chromogenic ELISA. The von Willebrand factor antigen (VWF:Ag) and collagen binding (VWF:CB) were also measured. Clinical complications and correlations with liver function biomarkers were also assessed. ADAMTS13 activity significantly decreased during surgery, with mean values markedly decreasing from preoperative to postoperative measurements ( = 0.01). A clear inverse relationship between ADAMTS13 activity and the VWF:CB/VWF:AG ratio was observed, indicating that increased high-molecular-weight VWF multimers are associated with decreased ADAMTS13 activity. Correlation analyses (CHE, Spearman's rho = 0.39) indicated that the reduction in ADAMTS13 activity was not attributable to impaired liver synthesis but likely resulted from peripheral consumption, potentially influenced by surgical stress. Perioperative reductions in ADAMTS13 activity are associated with an accumulation of high-molecular-weight VWF multimers and a higher incidence of postoperative complications. These results demonstrate that ADAMTS13 could be a useful perioperative risk biomarker for cardiac surgery patients.

摘要

具有血小板反应蛋白1型基序的解聚素和金属蛋白酶13(ADAMTS13)通过裂解血管性血友病因子(VWF)多聚体来调节止血。ADAMTS13-VWF轴失调会导致不同的血栓形成情况。本研究调查了心脏大手术期间ADAMTS13活性的变化及其与VWF变化和临床并发症的关系。对168例接受心脏手术的患者进行了总共628次ADAMTS13活性和抑制剂测量。在麻醉开始后以及术后每天最多6天通过Technozym显色ELISA法测量ADAMTS13活性。还测量了血管性血友病因子抗原(VWF:Ag)和胶原结合(VWF:CB)。还评估了临床并发症以及与肝功能生物标志物的相关性。手术期间ADAMTS13活性显著降低,平均值从术前测量到术后测量明显下降( = 0.01)。观察到ADAMTS13活性与VWF:CB/VWF:AG比值之间存在明显的负相关关系,表明高分子量VWF多聚体增加与ADAMTS13活性降低有关。相关性分析(CHE,Spearman等级相关系数 = 0.39)表明,ADAMTS13活性的降低并非归因于肝脏合成受损,而是可能源于外周消耗,可能受手术应激影响。围手术期ADAMTS13活性降低与高分子量VWF多聚体的积累以及术后并发症的较高发生率相关。这些结果表明,ADAMTS13可能是心脏手术患者有用的围手术期风险生物标志物。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4188/12295668/b8552ec2c83d/jcm-14-04936-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4188/12295668/c2b592584832/jcm-14-04936-g001.jpg
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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4188/12295668/bc6bff891c0d/jcm-14-04936-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4188/12295668/b8552ec2c83d/jcm-14-04936-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4188/12295668/c2b592584832/jcm-14-04936-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4188/12295668/a4e39bb9cef3/jcm-14-04936-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4188/12295668/ffdfd6ed3d39/jcm-14-04936-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4188/12295668/bc6bff891c0d/jcm-14-04936-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4188/12295668/b8552ec2c83d/jcm-14-04936-g005.jpg

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本文引用的文献

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J Clin Med. 2025 Apr 30;14(9):3105. doi: 10.3390/jcm14093105.
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Atypical Hemolytic Uremic Syndrome: A Review of Complement Dysregulation, Genetic Susceptibility and Multiorgan Involvement.非典型溶血性尿毒症综合征:补体失调、遗传易感性及多器官受累综述
J Clin Med. 2025 Apr 7;14(7):2527. doi: 10.3390/jcm14072527.
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Anti-ADAMTS13 Autoantibodies in Immune-Mediated Thrombotic Thrombocytopenic Purpura.
免疫介导的血栓性血小板减少性紫癜中的抗ADAMTS13自身抗体
Antibodies (Basel). 2025 Mar 10;14(1):24. doi: 10.3390/antib14010024.
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VWF-ADAMTS13 imbalance bridges infection to stroke.血管性血友病因子-凝血酶原酶解素13失衡将感染与中风联系起来。
Blood Adv. 2025 Mar 25;9(6):1342-1343. doi: 10.1182/bloodadvances.2024015665.
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2024 EACTS/EACTAIC/EBCP Guidelines on cardiopulmonary bypass in adult cardiac surgery.2024年欧洲心胸外科学会/欧洲成人先天性心脏病协会/欧洲心脏麻醉与围术期学会成人心脏手术体外循环指南。
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