Piyush Ojha, MBBS, MD, DM
Stroke accounts for approximately 10% of all deaths worldwide and leads to substantial long-term disability. The majority of the strokes are ischemic in origin. No identifiable cause is found in up to one-third of the patients after a standard evaluation, which limits the options for secondary stroke prevention. Mechanical thrombectomy has been found to be highly effective in patients with large vessel occlusions (LVO). In addition to the revascularisation, endovascular procedures have also created a unique opportunity to identify the likely stroke pathogenesis by providing thrombus material for further study. Emerging insights on various thrombus characteristics can not only provide valuable information that might be useful for guiding acute therapies, but also in optimizing secondary stroke prevention, as different components in the clot may respond to different pharmacological strategies.
Studies have tried to correlate thrombus histological composition and stroke pathogenesis. Sporns et al.1 observed that clots from a cardioembolic source had a higher proportion of fibrin/platelets and fewer red blood cells than noncardioembolic thrombi.
Fitzgerald et al.2 in this study assessed histological clot composition in a series of patients with large vessel occlusion and analysed correlation between clot composition and stroke pathogenesis. The study collected clots from patients (>18 years) undergoing mechanical thrombectomy for LVO as a part of the STRIP registry (Stroke Thromboembolism Registry of Imaging and Pathology). After immediate fixation in 10% phosphate buffered formalin, clots were shipped to a central core laboratory for standard tissue processing. Thin sections (3-5 µm) were prepared after embedding in paraffin and were stained with hematoxylin and eosin and Martius Scarlett Blue stains. Software analysis was used for histological quantification (platelet, RBC, fibrin, WBC). Demographic data was collected, and stroke pathogenesis was classified using the TOAST (Trial of ORG 10172 in Acute Stroke Treatment) system.
The study included 105 patients. Ninety-eight percent of patients achieved successful reperfusion (TICI 2b/3 score) with an overall mean number of passes 2.1. Almost half of the patients had a cardioembolic source for the embolus. The proportion of patients with a large artery atherosclerotic (LAA) and cryptogenic source was almost similar (one-fifth).
Clots from the patients with LAA strokes had a significantly higher mean platelet content than those with cardioembolic source (P=0.03) and non-significantly higher platelet content than cryptogenic strokes (P=0.74). Platelets count in clots with cardioembolic strokes was lower than cryptogenic stroke, although not significant. A statistically significant proportion of LAA strokes clots were platelet rich compared to cardioembolic strokes (55.0% versus 21.2%; P=0.005). Similarly, cryptogenic strokes had a significantly higher proportion of platelet rich clots than cardioembolic cases (50.0% versus 21.2%; P=0.024). LAA and cryptogenic strokes had a similar proportion of platelet-rich clots.
The authors, hence, concluded that clots in the patients with strokes secondary to LAA and cryptogenic source were more likely to be platelet rich than cardioembolic strokes.
The study had some limitations, like possibility of inter-site variability in the reporting of the suspected stroke pathogenesis. Another important limitation is that Martius Scarlett Blue stain cannot differentiate between platelets and other potentially key platelet-related factors such as von Willebrand factor, which may contribute to a significant proportions of clot composition, hence leading to incorrect observations.
Further large-scale studies may aid in identifying the pathogenesis, especially in cryptogenic strokes, along with guiding the management (antiplatelet vs anticoagulation) depending on histological characteristics of the retrieved clot.
References:
- Sporns PB, Hanning U, Schwindt W, Velasco A, Minnerup J, Zoubi T, et al. Ischemic stroke: what does the histological composition tell us about the origin of the thrombus? Stroke. 2017; 48:2206–2210.
- Fitzgerald S, Dai D, Wang S, Douglas A, Kadirvel R, Layton KF, et al. Platelet-Rich Emboli in Cerebral Large Vessel Occlusion Are Associated With a Large Artery Atherosclerosis Source. Stroke. 2019;50:1907–1910.
