Abstract
Thrombosis is a major complication of cardiovascular disease, leading to myocardial infarction, acute ischemic stroke, or venous thromboembolism. Thrombosis occurs when a thrombus forms inside blood vessels disrupting blood flow. Developments in thrombectomy to remove thrombi from vessels have provided new opportunities to study thrombus composition which may help to understand mechanisms of disease and underpin improvements in treatments. We aimed to review thrombus compositions, roles of components in thrombus formation and stability, and methods to investigate thrombi. Also, we summarize studies on thrombus structure obtained from cardiovascular patients and animal models. Thrombi are composed of fibrin, red blood cells, platelets, leukocytes, and neutrophil extracellular traps. These components have been analyzed by several techniques, including scanning electron microscopy, laser scanning confocal microscopy, histochemistry, and immunohistochemistry; however, each technique has advantages and limitations. Thrombi are heterogenous in composition, but overall, thrombi obtained from myocardial infarction are composed of mainly fibrin and other components, including platelets, red blood cells, leukocytes, and cholesterol crystals. Thrombi from patients with acute ischemic stroke are characterized by red blood cell- and platelet-rich regions. Thrombi from patients with venous thromboembolism contain mainly red blood cells and fibrin with some platelets and leukocytes. Thrombus composition from patients with myocardial infarction is influenced by ischemic time. Animal thrombosis models are crucial to gain further mechanistic information about thrombosis and thrombus structure, with thrombi being similar in composition compared with those from patients. Further studies on thrombus composition and function are key to improve treatment and clinical outcome of thrombosis.
Highlights
Thrombosis is a major complication of cardiovascular disease, leading to myocardial infarction, acute ischemic stroke, or venous thromboembolism
Changes in clot structure are of key interest due to associations with risk of myocardial infarction (MI), acute ischemic stroke (AIS), and venous thromboembolism (VTE)
Histology indicated that white thrombi from patients with ST-segment–elevation MI (STEMI) were mainly composed of fibrin, whereas red thrombi were mainly composed of red blood cells (RBCs).[7]
Summary
Thrombosis is a major complication of cardiovascular disease, leading to myocardial infarction, acute ischemic stroke, or venous thromboembolism. Thrombi are heterogenous in composition, but overall, thrombi obtained from myocardial infarction are composed of mainly fibrin and other components, including platelets, red blood cells, leukocytes, and cholesterol crystals. Changes in clot structure are of key interest due to associations with risk of myocardial infarction (MI), acute ischemic stroke (AIS), and venous thromboembolism (VTE). Principal components of thrombi include fibrin, platelets, red blood cells (RBCs), leukocytes, and neutrophil extracellular traps (NETs). High thrombin concentrations lead to dense fibrin networks that are relatively resistant to fibrinolysis.[2] Previous in vitro studies have linked changes in fibrin clot structure,[1] viscoelastic properties,[4] and hypofibrinolysis[5] to thrombosis. Instead of forming 3-dimensional fiber networks, fibrin molecules align into continuous films forming a protective layer across the surface of clots, Highlights
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