The widespread adoption of mechanical thrombectomy has enabled the analysis of thrombi retrieved from patients with acute ischemic stroke (AIS). There is growing interest in the relationship between thrombi composition, including red blood cell (RBC), fibrin/other components (F/O), white blood cell (WBC) ratios, and stroke etiology (1). Identifying the etiology of stroke is crucial for secondary prevention. Arterial dissection, a prevalent cause of stroke in young patients (2), may exhibit diagnostically significant thrombi characteristics. Studies have primarily focused on the compositional differences among cardioembolism (CE), large artery atherosclerosis (LAA), and stroke of undetermined etiology (SUE), revealing significant heterogeneity (3, 4). However, systematic investigations that specifically address thrombi compositions in cases of arterial dissection are scarce. Therefore, this study aimed to characterize dissection thrombi compositions and compare them with those of non-dissection thrombi to explore the differences in thrombi compositions across various stroke etiologies.

Among the 230 patients with AIS, 16 (7.0%) had arterial dissection-related stroke, and 214 (93.0%) had non-dissection etiologies. The non-dissection group comprised 59 LAA cases, 124 CE cases, two SOE cases (patients with confirmed non-dissection etiologies: 1 carotid stent thrombosis and 1 systemic lupus erythematosus-related stroke), and 29 SUE cases. The patients in the dissection group were significantly younger than those in the non-dissection group (45 vs. 66 years, p < 0.001) and exhibited a lower prevalence of hypertension (12.5% vs. 53.5%, p = 0.002) and atrial fibrillation (0% vs. 50.5%, p < 0.001). Tandem lesions were predominantly observed in the dissection group (100% vs. 18.2%, p < 0.001). The proportion of extracranial artery stent implantation was higher in the dissection group (81.2% vs. 8.9%, p < 0.001). No intergroup differences were observed in other variables (sex, diabetes, dyslipidemia, admission NIHSS score, anterior or posterior circulation involvement, intracranial/extracranial occlusion or intravenous thrombolysis, mechanical thrombectomy technique, number of passes, intracranial primary balloon angioplasty and stent placement, and extracranial primary balloon angioplasty; all p > 0.05) (Table 1).

Subgroup analyses identified distinct phenotypic and procedural signatures in stroke etiology. The patients with arterial dissection were the youngest (vs. LAA/CE/SUE; all p < 0.05), with dissection and LAA showing a higher male prevalence than did CE (p < 0.05). Vascular risk factors followed etiology-specific gradients: hypertension decreased stepwise (LAA > CE > dissection; p < 0.05), whereas atrial fibrillation was most frequent in the CE group (vs. LAA/SUE/dissection; all p < 0.001). The lifestyle factors differed as follows: smoking (LAA > CE, p < 0.05) and alcohol use (LAA > CE/SUE, p < 0.05) increased in the LAA group. The NIHSS score was lower in the LAA group than in the CE group (p < 0.05) but was comparable between the LAA and dissection/SUE groups. Procedural variations included higher stent retriever use in the LAA group (vs. dissection, CE, or SUE; p < 0.05) and increased intracranial balloon angioplasty/stenting in the LAA vs. non-LAA group (p < 0.05). Extracranial stenting peaked in dissection (vs. all groups; p < 0.01), whereas balloon angioplasty was dominant in LAA (vs. CE/SUE; p < 0.001) and dissection (vs. CE; p = 0.023). Supplementary Table 1 shows the clinical comparisons.

Histopathological analyses revealed no significant differences between the dissection and non-dissection groups in the RBC% (55.9% vs. 49.8%), F/O% (38.6% vs. 45.9%), WBC% (3.5% vs. 3.9%), or total thrombus area (31.3 mm² vs. 15.8 mm²) (p > 0.05). Similarly, subgroup comparisons revealed no significant differences in the RBC%, F/O%, and WBC% (p > 0.05). The total thrombus area was significantly smaller in the LAA group (10.5 mm²) than in the CE (17.7 mm²) and dissection groups (31.3 mm²) (p < 0.05). There was no notable difference in the total thrombus area between the dissection and CE groups (p > 0.05) (Table 2 and Figure 3).

Arterial dissection is a mechanical vascular injury caused by an intimal tear that creates a false lumen, leading to local thrombus formation and potential distal embolization. Dissection involves different mechanisms than atherothrombotic events resulting from plaque rupture or cardioembolic events resulting from atrial fibrillation. In the present study, distinct risk profiles were observed among the patient groups: patients with arterial dissection were the youngest and had the least hypertension; patients with LAA had strong associations with vascular risk factors such as hypertension, smoking, and alcohol use; and patients with CE showed the highest rates of atrial fibrillation. These patterns align with their respective pathophysiological mechanisms—mechanical or genetic in dissection, atherosclerosis in LAA, and cardiac embolism in CE—highlighting the need for targeted prevention and treatment strategies.

Previous studies on thrombus composition and stroke etiology have predominantly focused on CE, LAA, and SUE sources (4, 10). However, the findings have been inconsistent. Kim et al. reported that clots from CE have a significantly higher proportion of RBCs and lower proportion of fibrin than those from LAA (11). In contrast, another study reported that LAA thrombi had the highest percentages of RBCs, CE, and SUE (12). The discrepancies in these findings may be attributed to the limited statistical power in previous studies, which often resulted from small sample sizes. Furthermore, the nonuniform distribution of thrombus components may undermine the representativeness of individual histological sections, especially when sample sizes are insufficient. It has been suggested that, for compositional analyses in large-scale studies, one thrombus section per case is adequate, whereas three sections per case have been recommended in smaller cohorts (8). Variations in image analysis software may also contribute to discrepancies in results. Thrombi associated with arterial dissection remain underexplored. The Stroke Thromboembolism Registry of Imaging and Pathology study (13), which examined thrombi from 1,350 patients with AIS using Martius Scarlet Blue staining, reported a higher RBC content in arterial dissection thrombi than in those from LAA and CE (50% vs. 46% vs. 42%; p < 0.01). However, this study primarily assessed the compositional differentiation between LAA and CE thrombi rather than the diagnostic utility for arterial dissection. Theoretically, arterial dissection thrombi may exhibit distinct compositional profiles compared to thrombi of other etiologies; however, the composition of arterial dissection thrombi is influenced by various factors, such as the extent of the intimal tear, hemodynamic conditions, and age of the thrombus, which likely contribute to their intrinsic heterogeneity. We observed a higher proportion of RBCs in the dissection thrombi than in the LAA and CE (55% vs. 49% vs. 50%). However, this difference was not statistically significant, implying that the conventional histological evaluation of cellular composition has limited efficacy in distinguishing stroke etiologies. Notably, RBC-rich thrombi tend to have a softer consistency and are more vulnerable to fragmentation, leading to distal embolization (1). This may explain the higher incidence of tandem lesions in the dissection group than in the non-dissection group observed in this study.

An assessment of thrombus burden is critically important for guiding endovascular treatment strategy selection and predicting clinical outcomes. Current standard evaluation methods primarily rely on non-contrast computed tomography or computed tomography angiography (14, 15); however, these radiologically estimated burdens lack validation for physically retrieved thrombi. Area analyses of representative sections of the retrieved thrombi in this study revealed that thrombi associated with LAA exhibited the smallest cross-sectional area, which was significantly smaller than those associated with CE or dissection. This may reflect differences in the context of thrombosis. LAA occlusions typically represent acute thrombosis superimposed on underlying stenosis, forming rapidly via platelet aggregation in a high-shear environment, resulting in compact, adherent thrombi, where even small volumes can cause complete occlusion. CE thrombi, however, form slowly under low-shear conditions, driven by thrombin-mediated coagulation with greater growth potential. Dissection-related thrombi develop within the false lumen, which may extend longitudinally, facilitating larger thrombus volumes. These observed differences in thrombus area may inform thrombectomy device selection; smaller LAA thrombi may be more amenable to stent retrievers, while larger CE or dissection thrombi might be better suited for aspiration thrombectomy. Notably, among the 88 patients excluded because of non-retrieved thrombi, 76 (86.4%) were LAA cases, suggesting a lower thrombus burden in the LAA. Rather than thrombus absence, these small thrombi may fragment and migrate distally; when advancing microcatheters/microwires through occluded arteries, fresh thrombus fragments can be pushed into patent distal segments, where endogenous lysis occurs (16). In such scenarios, successful reperfusion was achieved either by direct primary balloon angioplasty and/or stenting, despite mechanical thrombectomy attempts without thrombus retrieval. Furthermore, thrombi classified as SUE demonstrated a significantly larger mean area than did the LAA thrombi, providing evidence that potentially supports a non-LAA origin in a subset of SUE cases.

This study has several limitations: (1) Only retrieved thrombus portions were analyzed, and unretrieved thrombus fragments may have affected the results; (2) the spatial heterogeneity (17) of thrombi may have limited the representativeness of two-dimensional sections for the overall composition; and (3) H&E staining cannot reliably differentiate fibrin from platelets, and it is unclear whether these components differ between arterial dissection and other causes, necessitating further immunohistochemical validation.

This study demonstrated the absence of significant compositional differences between the thrombi associated with arterial dissection-related stroke and those associated with non-dissection stroke. The findings suggest that conventional histopathological staining has limited efficacy in distinguishing dissection from other etiologies. Notably, the thrombi resulting from dissection, CE, and SUE exhibited significantly larger areas than those resulting from LAA, indicating a greater thrombus burden. These findings may have important implications for the optimization of mechanical thrombectomy strategies.