Mechanical behavior of in vitro blood clots and the implications for acute ischemic stroke treatment

Abstract

BackgroundClot mechanical properties are influenced by composition and the arrangement of components within the clot. This work investigates the effects of platelet-driven contraction on blood clot microstructure and mechanical behavior, and provides insight into some implications for mechanical thrombectomy.MethodsPlatelet-contracted clot analogues (PCCs) and non-contracted clot analogues (NCCs) were prepared from blood mixtures of various hematocrits (%H), that is, the volume percentage of red blood cells (RBCs) in the mixture. Mechanical testing was performed to compare the behavior of the analogues with previously tested human thromboemboli. Scanning electron microscopy and histology investigated the clot microstructure and composition. The association between clot properties and their behavior during mechanical behavior was also investigated.ResultsOverall, PCCs were found to be stiffer than NCCs, across all hematocrits. PCCs with a low %H resisted complete ingestion via contact aspiration alone or complete retrieval with stent-retrievers. PCCs with a higher %H and all NCCs were fully retrievable, although the likelihood of fragmentation was increased in clots with a greater %H. Histologically, there was little difference in the RBC and fibrin content between PCCs and NCCs with the same %H. However, the microstructure of the two groups differed significantly.ConclusionA selection of repeatable clot analogues with a range of mechanical properties have been developed for in vitro modeling of acute ischemic stroke. Platelet contraction significantly affects clot volume and microstructure, and in turn clot stiffness. The significant difference in mechanical properties and microstructure, but without an appreciable difference in histology, implies that histological studies of explanted human clots alone may not prove to be predictive of the mechanical behavior of the clots in thrombectomy.

Development of an in vitro model of calcified cerebral emboli in acute ischemic stroke for mechanical thrombectomy evaluation

“…The first consisted of the above-described bone fragments only, and the latter were prepared by forming a thrombus around a bone fragment. Venous ovine blood was collected using methods similar to those reported previously 24 25. Platelet-rich plasma was isolated from the citrated blood by spinning at 180 g for 10 min.…”

“…Platelet-rich plasma was isolated from the citrated blood by spinning at 180 g for 10 min. The remaining fraction of blood was spun again at 2200 g to isolate the red blood cells (RBCs) 25. A blood mixture of 1% hematocrit, the volume percentage of RBCs in the mixture, was created with the platelet-rich plasma and RBCs.…”

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

“…Intra-arterial Mechanical Thrombectomy (MT) is a minimally invasive procedure for treatment of AIS in which the obstructing thrombus is removed using a stent-retriever and/or an aspiration catheter. Based on the recent clinical studies [2,3,[12][13][14][15][16][4][5][6][7][8][9][10][11] the proportion of patients experiencing successful procedural revascularization (TICI >=2b) ranged from 76% [17] to 85.4% [18] after all procedures. Although complete revascularization (TICI =3) is achieved in less than 61% of cases [19], and it often takes multiple attempts to remove the complete thrombus.…”

Characterizing thrombus with multiple red blood cell compositions by optical coherence tomography attenuation coefficient

“…During the coagulation process, water was absorbed by the formed fibrin network and was stored within the swollen fibrin. Once the clots were pulled from the syringe during the experiments, the water in fibrin network starts to weep from each phenotype clot in different ways with respect to time [60]. Each fibrin network in clots is independent, and the rate of water extracting from the fibrin network could be different.…”