Thrombus thrombi
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Summary
10 papers analyzed
These studies suggest that thrombus composition, including fibrin, platelets, red blood cells, leukocytes, and cholesterol crystals, impacts the efficacy of treatments and clinical outcomes, and that understanding these components can improve diagnosis, treatment, and management of thrombosis.
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Understanding Thrombus Composition and Its Impact on Thrombosis and Thrombolysis
Thrombus Composition in Acute Ischemic Stroke
Thrombi retrieved from patients with acute ischemic stroke exhibit significant heterogeneity in their composition. These thrombi typically contain a mix of fibrin, platelets, red blood cells (RBCs), von Willebrand Factor (VWF), and neutrophil extracellular traps (NETs). The composition of these thrombi can significantly impact the efficacy of mechanical thrombectomy and thrombolysis. Fibrin-rich clots, for instance, are associated with increased recanalization maneuvers, longer procedure times, and less favorable clinical outcomes compared to RBC-rich clots.
Visualizing Thrombus Structure and Dynamics
Recent advancements in imaging technologies have enabled better visualization and understanding of thrombus structure. Intravital imaging methodologies combined with mechanical thrombectomy have allowed for the extraction and microscopic examination of fresh thrombi. These studies have revealed that thrombi contain various structural forms of fibrin, platelet aggregates, leukocytes, and RBCs, many of which acquire a polyhedral shape due to intravital platelet-driven contraction. Additionally, visible-light optical coherence tomography (vis-OCT) has been used to monitor the dynamic process of thrombus formation in a microfluidic blood vessel-on-chip device, providing insights into the spatial and temporal behavior of thrombi in flowing blood.
Thrombus Composition in Cardiovascular Diseases
Thrombi in cardiovascular diseases such as myocardial infarction, acute ischemic stroke, and venous thromboembolism show distinct compositional characteristics. Thrombi from myocardial infarction patients are mainly composed of fibrin, platelets, RBCs, leukocytes, and cholesterol crystals. In contrast, thrombi from acute ischemic stroke patients are characterized by RBC- and platelet-rich regions, while those from venous thromboembolism patients contain mainly RBCs and fibrin with some platelets and leukocytes. The composition of thrombi can influence their stability and the clinical outcomes of thrombosis.
Role of Platelet Receptors and Signaling in Thrombus Formation
Platelet receptors and their signaling pathways play a crucial role in the dynamics of thrombus formation. Initial tethering and firm adhesion of platelets to the exposed subendothelium are mediated by glycoprotein (GP) Ib/IX/V complex and collagen receptors, GP VI and α2β1 integrin, in the platelet surface, and by VWF and fibrillar collagen in the vascular site. These interactions trigger signaling events that reinforce adhesion and promote platelet activation, leading to thrombus stabilization.
Factor XIII and Red Blood Cell Retention in Venous Thrombi
The activity of the transglutaminase factor XIII (FXIII) is critical for RBC retention within venous thrombi, directly affecting thrombus size. Studies have shown that FXIII-deficient mice produce smaller thrombi with fewer RBCs compared to wild-type mice. This indicates that FXIII plays a central role in venous thrombogenesis and could be a potential therapeutic target for limiting venous thrombosis.
Neutrophil Extracellular Traps in Thrombi
NETs, composed mainly of DNA and citrullinated histones, are released by activated neutrophils and modify the stability and lysability of fibrin in thrombi. The NET content of thrombi varies with the type of arterial disease and correlates with systemic inflammatory markers and patient age. These variations in NET-related thrombus structure can affect both the spontaneous progress and therapeutic outcomes of ischemic arterial diseases.
Blood-Borne Tissue Factor and Thrombus Propagation
Blood-borne tissue factor (TF) plays a significant role in thrombus propagation at the site of vascular injury. Studies have shown that TF-positive membrane vesicles, often derived from leukocytes, are inherently thrombogenic and contribute to thrombus formation. This highlights the importance of TF in the coagulation process and its potential as a target for therapeutic intervention .
Conclusion
Understanding the composition and dynamics of thrombi is crucial for improving the treatment and clinical outcomes of thrombosis. Advances in imaging technologies and molecular studies have provided valuable insights into the structural and functional characteristics of thrombi. These findings underscore the importance of considering thrombus heterogeneity in the development of more effective therapeutic strategies for thrombolysis and thrombectomy.
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