Bechtel Grace N, Sugerman Gabriella P, Eades Tatum, Malinowska Zuzanna, Bush Adam M, Saber Hamidreza, Parekh Sapun H, Rausch Manuel K
Department of Biomedical Engineering, The University of Texas at Austin, Austin, TX, 78712, USA.
Department of Biomedical Engineering, San José State University, San Jose, CA, 95192, USA.
Adv Healthc Mater. 2025 Apr;14(9):e2403389. doi: 10.1002/adhm.202403389. Epub 2025 Feb 21.
Thromboembolic diseases are a significant cause of mortality and are clinically treated enzymatically with tissue plasminogen activator (tPA). Interestingly, prior studies in fibrin fibers and fibrin gels have demonstrated that thrombolysis may be mechanically sensitive. This study aims to expand mechano-lytic studies to whole blood clots. Furthermore, this study investigates not only how mechanics impacts lysis but also how lysis impacts mechanics. Therefore, clots made from whole human blood are exposed to tPA while the clots are either stretched or unstretched. After, the resulting degree of clot lysis is measured by weighing the clots and by measuring the concentration of D-dimer in the surrounding bath. Additionally, each clot's mechanical properties are measured. This study finds that mechanical stretch accelerates loss in clot weight but does not impact the lysis rate as measured by D-dimer. Moreover, lysis not only removes clot volume but also reduces the remaining clot's stiffness and toughness. In summary, tPA-induced lysis of whole clot appears mechanically insensitive, but stretch reduces clot weight. Furthermore, results show that thrombolysis weakens clot. This suggests that thrombolysis may increase the risk of secondary embolizations but may also ease clot removal during thrombectomy, for example.
血栓栓塞性疾病是导致死亡的重要原因,临床上使用组织纤溶酶原激活剂(tPA)进行酶促治疗。有趣的是,先前在纤维蛋白纤维和纤维蛋白凝胶中的研究表明,溶栓作用可能对机械力敏感。本研究旨在将机械溶解研究扩展至全血凝块。此外,本研究不仅探究机械力如何影响溶解,还研究溶解如何影响机械力。因此,用人全血制成的凝块在拉伸或未拉伸状态下接触tPA。之后,通过称量凝块以及测量周围浴液中D - 二聚体的浓度来测定凝块的溶解程度。此外,还测量每个凝块的机械性能。本研究发现,机械拉伸会加速凝块重量的损失,但不会影响以D - 二聚体测量的溶解速率。此外,溶解不仅会减少凝块体积,还会降低剩余凝块的硬度和韧性。总之,tPA诱导的全凝块溶解似乎对机械力不敏感,但拉伸会减轻凝块重量。此外,结果表明溶栓作用会使凝块变弱。这表明溶栓作用可能会增加继发性栓塞的风险,但例如在血栓切除术期间也可能便于凝块清除。
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