Shell Versus Core Architecture and Biology of Thrombi in Acute Ischemic Stroke: A Systematic Review

BACKGROUND: The presence of an outer shell has been recently described as a common feature of acute ischemic stroke (AIS) thrombi. We performed a systematic review of the current literature on shell genesis, structure, and clinical significance. METHODS: Following PRISMA guidelines, we searched Ovid Cochrane Central Register of Controlled Trials, Embase, Medline, Scopus, and Web of Science for studies reporting the composition and structure of AIS thrombi and clot analogs. Identified studies were added to Covidence software for primary screening. Two reviewers independently screened titles and abstracts followed by full-text screening. RESULTS: From 1290 identified studies, 10 were included in this review. Studies using histology/immunohistochemistry/immunofluorescence described fibrin, platelets, von Willebrand factor, and neutrophil extracellular traps as the main components of the shell. Scanning electron microscopy demonstrated a dense, compact fibrin/platelet-rich shell, and a core rich in polyhedrocytes. Microfluidics studies identified highly activated P-selectin-positive platelets and fibrin forming the core while secondary agonists adenosine diphosphate and thromboxane, along with loosely packed P-selectin-negative platelets constituted the shell. CONCLUSIONS: The composition, compaction, and integrity of the shell may impact thrombolysis and revascularization outcomes. The preponderance of studies supported this conclusion.