Background Clot 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.
Methods Platelet-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.
Results Overall, 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.
Conclusion A 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.
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PEM and MG are joint senior authors.
Contributors SJ: clot preparation, study design, data collection, data analysis and interpretation, manuscript writing and editing. JC and MJG: experimental conception and design. RMC: clot preparation, study design, data interpretation, manuscript editing. PEM, JPM: interpretation of the results, manuscript editing. MG: initial concept of forming clot analogues, manuscript editing. All authors provided suggestions and feedback on the manuscript, and approved the final manuscript.
Funding This work was supported by Cerenovus, the Irish Research Council (Grant No. EPSPG/2015/92) and the NUI Galway Hardiman Research Scholarship.
Competing interests SJ reports grants from the Irish Research Council and the NUI Galway Hardiman Research Scholarship during the conduct of the study, and reports financial support from Cerenovus, outside the submitted work. RMC, MG report a financial relationship with Cerenovus outside the submitted work. JPM reports non-financial support from Cerenovus, outside the submitted work. JC reports fee-for-service consulting for Stryker Neurovascular and InNeuroCo Inc. MJG has been a consultant on a fee-per-hour basis for Cerenovus, Imperative Care, MIVI Neurosciences, phenox, Route 92 Medical, Stryker Neurovascular; holds stock in Imperative Care and Neurogami; and has received research support from the National Institutes of Health (NIH), the United States – Israel Binational Science Foundation, Anaconda, Cerenovus, Cook Medical, Gentuity, Imperative Care, InNeuroCo, Magneto, Microvention, Medtronic Neurovascular, MIVI Neurosciences, Neuravi, Neurogami, Philips Healthcare, Rapid Medical, Route 92 Medical, Stryker Neurovascular, Syntheon, and the Wyss Institute.
Patient consent for publication Not required.
Provenance and peer review Not commissioned; externally peer reviewed.
Data availability statement Please contact the corresponding author with data sharing requests.
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