Clot Composition and Ischemic Stroke Etiology: A Contemporary Narrative Review

Acute ischemic stroke (AIS) is one of the leading global causes of mortality and morbidity. Clearer understanding of stroke etiology is a major clinical objective to determine appropriate strategies for secondary stroke prevention. Histological and molecular analysis of clots retrieved during mechanical thrombectomy (MT) in AIS offers a unique opportunity to study clot composition and its relation to stroke etiology. The field of clot composition analysis has undergone substantial growth in recent years, driven in part by the establishment of MT as the standard of care, as well as its expanding indications. Although many features differ between large-artery atherosclerosis (LAA) and cardioembolic (CE) clots, application of these findings to predicting stroke etiology at a clinical level remains challenging. Moreover, a significant number of patients have multiple comorbidities or suffer a cryptogenic subtype. Next-generation techniques such as multiomic sequencing offer a powerful potential to elevate our understanding of clot pathology and provide the level of granularity required for clinical diagnosis and management. Herein, we provide an updated review of the current state of the field by exploring stroke etiologies and their relationship to clot pathology, including classic histologic features as well as more recent, emerging results from proteomic and transcriptomic analyses.