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Measuring the effect of thrombosis, thrombus maturation and thrombolysis on clot mechanical properties in an in-vitro model
Journal of Biomechanics ( IF 2.4 ) Pub Date : 2021-09-06 , DOI: 10.1016/j.jbiomech.2021.110731
Anushree Dwivedi 1 , Aoife Glynn 1 , Sarah Johnson 2 , Sharon Duffy 3 , Behrooz Fereidoonnezhad 4 , Patrick McGarry 4 , Michael Gilvarry 1 , Ray McCarthy 1 ,
Affiliation  

Changes in acute ischemic stroke thrombi structure and composition may result in significant differences in treatment responsiveness. Ischemic stroke patients are often treated with a thrombolytic agent to dissolve thrombi, however these patients may subsequently undergo mechanical thrombectomy to remove the occlusive clot. We set out to determine if rt-PA thrombolysis treatment of blood clots changes their mechanical properties, which in turn may impact mechanical thrombectomy. Using a design-of-experiment approach, ovine clot analogues were prepared with varying composition and further exposed to different levels of compaction force to simulate the effect of arterial blood pressure. Finally, clots were treated with three r-tPA doses for different durations. Clot mass and mechanical behaviour was analysed to assess changes due to (i) Platelet driven contraction (ii) Compaction force and (iii) Thrombolysis. Clots that were exposed to r-tPA for longer duration showed significant reduction in clot mass (p < 0.001). Exposure time to r-tPA (p < 0.001) was shown to be an independent predictor of lower clot stiffness. A decrease in energy dissipation ratio during mechanical compression was associated with longer exposure time in r-tPA (p = 0.001) and a higher platelet concentration ratio (p = 0.018). The dose of r-tPA was not a significant factor in reducing clot mass or changing mechanical properties of the clots. Fibrinolysis reduces clot stiffness which may explain increased distal clot migration observed in patients treated with r-tPA and should be considered as a potential clot modification factor before mechanical thrombectomy.



中文翻译:

在体外模型中测量血栓形成、血栓成熟和溶栓对凝块机械性能的影响

急性缺血性卒中血栓结构和组成的变化可能导致治疗反应性的显着差异。缺血性中风患者通常用溶栓剂治疗以溶解血栓,但这些患者随后可能会接受机械血栓切除术以去除闭塞的凝块。我们着手确定血栓的 rt-PA 溶栓治疗是否会改变其机械特性,这反过来又可能影响机械取栓。使用实验设计方法,制备了具有不同成分的羊血凝块类似物,并进一步暴露于不同水平的压实力以模拟动脉血压的影响。最后,凝块用三种 r-tPA 剂量处理不同的持续时间。分析凝块质量和机械行为以评估由于 (i) 血小板驱动收缩 (ii) 压实力和 (iii) 血栓溶解引起的变化。长时间暴露于 r-tPA 的凝块显示凝块质量显着减少 (p < 0.001)。暴露于 r-tPA 的时间 (p < 0.001) 被证明是较低凝块刚度的独立预测因子。机械压缩过程中能量耗散率的降低与 r-tPA 中更长的暴露时间 (p = 0.001) 和更高的血小板浓度比 (p = 0.018) 相关。r-tPA 的剂量不是减少凝块质量或改变凝块机械性能的重要因素。

更新日期:2021-09-30
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