Blood clot fracture properties are dependent on red blood cell and fibrin content

Abstract

Thrombus fragmentation during endovascular stroke treatment, such as mechanical thrombectomy, leads to downstream emboli, resulting in poor clinical outcomes. Clinical studies suggest that fragmentation risk is dependent on clot composition. This current study presents the first experimental characterization of the fracture properties of blood clots, in addition to the development of a predictive model for blood clot fragmentation. A bespoke experimental test-rig and compact tension specimen fabrication has been developed to measure fracture toughness of thrombus material. Fracture tests are performed on three physiologically relevant clot compositions: a high fibrin 5% H clot, a medium fibrin 20% H clot, a low-fibrin 40% H clot. Fracture toughness is observed to significantly increase with increasing fibrin content, i.e. red blood cell-rich clots are more prone to tear during loading compared to the fibrin-rich clots. Results also reveal that the mechanical behaviour of clot analogues is significantly different in compression and tension.Finite element cohesive zone modelling of clot fracture experiments show that fibrin fibres become highly aligned in the direction perpendicular to crack propagation, providing a significant toughening mechanism. The results presented in this study provide the first characterization of the fracture behaviour of blood clots and are of key importance for development of next-generation thrombectomy devices and clinical strategies.

A new constitutive model for permanent deformation of blood clots with application to simulation of aspiration thrombectomy

“…The results suggest that the hyperelastic model overpredicts the maximum stress in the clot by 10-13%. The computed values of maximum principal stress for both models are lower than the critical values of crack initiation for different clot compositions (100-480 kPa), as reported in our previous study (Fereidoonnezhad et al, 2020a).…”

“…In (Fereidoonnezhad et al, 2021(Fereidoonnezhad et al, , 2020a we propose a framework for the elastic deformation and rotation of the fibrin network in the development of anisotropic hyperelastic behaviour of blood clots. In the current study we extend this framework to incorporate the permanent plastic deformation of clots due to formation and dissociation of cross-links in the fibrin network.…”

“…First pass revascularisation is associated with better clinical outcome. Revascularization in multiple passes leads to complications such as increased risk of distal embolization due to the clot fragmentation (Fereidoonnezhad et al, 2020a;Gralla et al, 2006;Kaesmacher et al, 2017;Po Sit, 2009). Moreover, a recent study shows that successful first pass recanalization in MT in US and EU reduces hospitalization and care costs in first year after stroke (Zaidat et al, 2020).…”

Development of a patient-specific cerebral vasculature fluid–structure-interaction model

“…Vessel material parameters are calibrated using published experimental stress-strain relationships for cranial vessels [21], resulting in the following It should be noted that the objective of the FSI simulation in this study is to demonstrate the capability of the developed platform and therefore these basic material models and parameters for the clot and artery are considered sufficient. More sophisticated material models such as those recently proposed for blood clots [23,24] and vessel walls [25] should be considered in future studies.…”

Experimental Evaluation of the Effectiveness of Aspiration-Based Techniques to Treat Different Types of Acute Thromboembolic Occlusions in the Femoropopliteal Vascular System Using an In Vitro Flow Model

“…Several studies examined thrombi extracted from patients with AIS and acute coronary syndrome (ACS), indicating such heterogeneous composition [19][20][21][22]. Here, composition seems to influence thrombus mechanics, which may affect a device's effectiveness [16,23,24]. Although data are lacking, this aspect seems to play a relevant role in peripheral thrombectomy, too.…”