Platelet-Neutrophil Association in NETs-Rich Areas in the Retrieved AIS Patient Thrombi.

Histological structure of thrombi is a strong determinant of the outcome of vascular recanalization therapy, the only treatment option for acute ischemic stroke (AIS) patients. A total of 21 AIS patients from this study after undergoing non-enhanced CT scan and multimodal MRI were treated with mechanical stent-based and manual aspiration thrombectomy, and thromboembolic retrieved from a cerebral artery. Complementary histopathological and imaging analyses were performed to understand their composition with a specific focus on fibrin, von Willebrand factor, and neutrophil extracellular traps (NETs). Though distinct RBC-rich and platelet-rich areas were found, AIS patient thrombi were overwhelmingly platelet-rich, with 90% of thrombi containing <40% total RBC-rich contents (1.5 to 37%). Structurally, RBC-rich areas were simple, consisting of tightly packed RBCs in thin fibrin meshwork with sparsely populated nucleated cells and lacked any substantial von Willebrand factor (VWF). Platelet-rich areas were structurally more complex with thick fibrin meshwork associated with VWF. Plenty of leukocytes populated the platelet-rich areas, particularly in the periphery and border areas between platelet-rich and RBC-rich areas. Platelet-rich areas showed abundant activated neutrophils (myeloperoxidase+ and neutrophil-elastase+) containing citrullinated histone-decorated DNA. Citrullinated histone-decorated DNA also accumulated extracellularly, pointing to NETosis by the activated neutrophils. Notably, NETs-containing areas showed strong reactivity to VWF, platelets, and high-mobility group box 1 (HMGB1), signifying a close interplay between these components.

Association of Major Adverse Cardiovascular Events in Patients With Stroke and Cardiac Wall Motion Abnormalities.

Background The association of cardiac wall motion abnormalities (CWMAs) in patients with stroke who have major adverse cardiovascular events (MACE) remains unclear. The purpose of this study was to estimate the 50-month risk of MACE, including stroke recurrence, acute coronary events, and vascular death in patients with stroke who have CWMAs. Methods and Results We performed a retrospective analysis of prospectively collected acute stroke data (acute stroke and transient ischemic attack) over 50 months by electronic medical records. Data included demographic and clinical information, vascular imaging, and echocardiography data including CWMAs and MACE. Of a total of 2653 patients with acute stroke/transient ischemic attack, CWMA was observed in 355 (13.4%). In patients with CWMAs, the embolic stroke of undetermined source (50.7%) was the most frequent index stroke subtype and stroke recurrences (P=0.001). In multivariate Cox regression after adjustment for demographics, traditional risk, and confounding factors, CWMA was independently associated with a higher risk of MACE (adjusted hazard ratio [HR], 1.74; 95% CI, 1.37-2.21 [P=0.001]). Similarly, CWMA independently conferred an increased risk for ischemic stroke recurrence (adjusted HR, 1.50; 95% CI, 1.01-2.17 [P=0.04]), risk of acute coronary events (aHR, 2.50; 95% CI, 1.83-3.40 [P=0.001]) and vascular death (adjusted HR, 1.57; 95% CI, 1.04-2.40 [P=0.03]), in comparison to the patients with stroke without CWMA. Conclusions In a multiethnic cohort of ischemic stroke with CWMA, CWMA was associated with 1.7-fold higher risks of MACE independent of established risk factors. Embolic stroke of undetermined source was the most common stroke association with CWMA. Patients with stroke should be screened for CWMA to identify those at higher risk of MACE.