## 4 Relationship Between LAA and Stroke
### Hemodynamic Characteristics of Left Atrial Appendage  
The process of thrombosis involves four key stages: vascular injury, platelet activation and aggregation, the coagulation cascade, and thrombus stabilization [74, 75]. Initially, following vascular injury, platelets rapidly accumulate at the damage site and become activated, releasing chemicals that encourage the recruitment of additional platelets. Next, the activation of clotting factors through a cascade results in the formation of a fibrin mesh, which further strengthens the thrombus. Finally, the thrombus contracts and stabilizes over time, forming a robust structure that prevents blood flow [5, 76]. [PERSON]'s triad is closely associated with this process [74, 77]. Endothelial injury initiates the entire thrombus formation process. Blood flow stasis prolongs the retention of platelets and clotting factors at the site of injury, promoting their activation. In a hypercoagulable state, due to increased clotting factors, the coagulation cascade is more easily triggered. Thus, analyzing the flow patterns in the LA/LAA becomes essential.  
Hemodynamics is closely linked to thrombus formation. When blood flow slows or eddies form, platelets more readily come into contact with the vessel wall and aggregate at sites of injury [7; 16; 78]. Low wall shear stress (WSS) can lead to endothelial dysfunction, while frequent changes in WSS direction are likely to trigger the activation of platelets, especially in areas with disturbed flow, such as bends or bifurcations [18; 37; 79]. In AF patients, irregular electrical signals reduce the contractility of the LA and decrease blood flow velocity. The peak flow velocity within the LAA is often less than 20 cm/s, promoting the accumulation and interaction of pro-coagulant factors, platelets, and red blood cells in this region [74; 80; 81]. Research shows that just 15 min of AF can increase thrombin levels, leading to a hypercoagulable state in the blood [82; 83; 84]. Several factors, including prolonged hemodynamic changes, atrial dilation, and fibrosis, can cause endothelial damage. This endothelial damage exposes matrix components, which enhance platelet adhesion and activation [85; 86]. These factors align with [PERSON]'s triad, explaining the elevated risk of thrombosis in AF patients.  
This review analyzes the hemodynamic mechanisms underlying [PERSON]'s triad, focusing on indicators related to the risk of stroke or thrombosis associated with the LAA. In Table 3, velocity stands out as the most direct and fundamental metric, measurable through both invasive and non-invasive imaging techniques. Research predominantly emphasizes mean LAA velocity, peak LAA velocity (both during emptying and filling phases), and peak LAA emptying velocity [7; 15; 78]. Nearly all studies acknowledge a substantial correlation between low flow velocity and the occurrence of AF, thrombosis, and stroke events.  
The LAA ejection fraction is generally assessed using transesophageal echocardiography (TEE) [35; 36]. The other indicators mentioned in Table 3 require simulation calculations based on geometric models. While attempts have been made to establish threshold values for these indicators to guide anticoagulant therapy, few studies provide such statistical thresholds.  
Moreover, increased left atrial pressure (LAP) is observed in AF patients and might serve as an independent predictor for AF recurrence [19; 87; 88]. Nevertheless, there is a lack of studies directly investigating the relationship between elevated LAP and the risks of stroke or thrombosis, highlighting an area for further exploration.