A journey into the insights of the clots retrieved in ischemic stroke
BY DR. MARCO BACIGALUPPI AND DR. AURORA SEMERANO
From Journal of Cerebral Blood Flow and Metabolism
The approval of endovascular procedures in 2015 to remove occlusive thrombi in large vessel stroke has revolutionized stroke care. Since the diffusion in clinical practice of endovascular procedures, extracted cerebral thrombi have become available. This material was before mostly inaccessible for analysis, with rare exceptions of post-mortem and experimental studies. Thus, over the last years, several centers have started to collected cerebral thrombi analysis purposes, and exciting research has rapidly grown on this topic. After all, ischemic stroke is due to a clot, and everyone knows how it is important to get insights into the pathogenic mechanisms of thrombosis.
A recent review article published in the Journal of Cerebral Blood Flow and Metabolism provides an overview of the main constituents of the human cerebral clots, comprehensively summarizes the existing literature on clot analysis, and critically focuses on its impact and its possible applications in clinical practice. How can a clump of coagulated blood help us advance knowledge about stroke mechanisms and ultimately improve stroke care?
Figure 1. Schematic picture of a cerebral thrombus with its main componts (image from Bacigaluppi et al. JCBFM, 10.1177/0271678X19856131)
Histopathologic assessment of cerebral clots might offer a glimpse into thrombus origin and define the cause of stroke. Indeed, clots that cause large vessel occlusion stroke can derive from a wide range of different sources (e.g., heart cavities or valves, atherosclerotic plaques or dissection of cervical arteries, venous thrombosis through paradoxical embolism). Despite intensive diagnostic workup, in up to 35% of cases, the source of stroke cannot be clarified, eliminating the opportunity for tailored prevention therapy. Thus, a first relevant potential application for clot analysis is to complement the diagnostic workup of stroke.
The clot's study can also unravel new targets for the development of new drugs to dissolve the thrombus in the acute phase of the stroke. Interestingly, new promising candidates have already emerged. Neutrophils are abundant in cerebral clots, and they may release Neutrophil Extracellular Traps, a web of extracellular DNA and proteins that act as a scaffold for thrombus formation and stabilization. Initial studies have shown that treatment with DNase, which operates on Neutrophil Extracellular Traps, can increase the lysis of human cerebral clots in ex-vivo experimental settings. Which other promising candidates are being discovered? Find More in the review article
Attempts to identify a signature of thrombus composition indirectly through Imaging are also on-going. It is indeed critical to predict thrombus composition in the acute stroke setting before clot retrieval. Consistent data report that a hyperdense artery sign in the baseline Computed Tomography scan or a Susceptibility Vessel Sign in Magnetic Resonance reveal the presence of a clot particularly enriched in red blood cells. In addition, also blood biomarkers are currently under investigation for prediction of clot composition; this field is in particular rapid evolution.
In summary, the JCBFM review article on cerebral thrombi highlights the importance of cerebral clot analysis as an emerging opportunity to complement the diagnostic workup of stroke, to develop new lytic approaches, and to optimize the acute treatment of stroke due to large vessel occlusion. Importantly, for their relevant, informative potential, retrieved clots should not be discarded after the endovascular procedure, whereas collaborative research projects are strongly encouraged. New interesting data are expected shortly. Will you also study retrieved thrombi?
Article details
Insights from thrombi retrieved in stroke due to large vessel occlusion
First Published June 18, 2019 Review Article
https://doi.org/10.1177/0271678X19856131
Journal of Cerebral Blood Flow & Metabolism
