Introduction: High rates of recanalization of Emergent Large Vessel Occlusion (ELVO) provide an opportunity to examine retrieved thrombi. We studied device and endothelial (ET) interactions to evaluate ET injury and the relationship between thrombi and Acute Ischemic Stroke (AIS) mechanism.
Methods: Prospective registry examining immunohistochemical characteristics of retrieved thrombi in ELVO patients. Thrombi were categorized histopathologically and ET injury quantified by CD34 staining and immunohistochemistry, ELISA and reverse transcribed quantitative PCR to detect ET components. ET mRNA expression of CD31 was quantified from thrombi RNA. Plasma at the thrombectomy site was tested for ET derived biomarkers: microparticles (MPs), soluble Intercellular Cell Adhesion Molecule-1 (sICAM1) and soluble Thrombomodulin (sTM). Statistical analysis was performed with unpaired student’s t-tests and chi-square tests.
Results: Twenty-five patients (age 68±3 , NIHSS 16±2, 48% female) were enrolled. The most common sites of occlusion were the MCA (9) and ICA (7). Eighty eight % of patients required three or less attempts at recanalization and 71 % achieved TICI 2b or 3. Histopathology demonstrated fibrin rich (5), erythrocytic (2), layered (7), and serpentine (11) thrombi and four were CD 34 positive. Levels of plasma biomarkers were: sTM 2.2±0.4 (<0.6-10.2ng/ml), MPs 101.4±18.4 (1.33-221nM), and sICAM1 160.0±19.8 (<15-406.1ng/ml). Patients with > 3 revascularization attempts had higher levels of sTM (5.5±0.4 vs 1.7±0.2, p<0.0002), sICAM (261.2±79.2 vs. 146.3±20.3, p<0.03), and CD31CT (27.7±0.8 vs 25.5±0.3, p < 0.03). Patients with PH 1 or 2 ICH had higher levels of microparticles than those without ICH or with HI 1 or 2 (203±19 vs 92±19, p<0.05). Patients with cardioembolic stroke had higher sTM (2.8±0.8 vs. 1.3±0.3, p<0.05) and sICAM1 levels (186±32 vs. 115±29, p<0.05) than those with carotid or intracerebral atherosclerosis.
Conclusions: ET markers can be detected in the retrieved thrombi and plasma milieu of ELVO patients. ET markers relate to increasing number of attempts at thrombectomy indicating ET disruption. sTM and sICAM are more common in patients with cardioembolic stroke and may serve as thrombus associated markers of AIS mechanism.