Thrombus Structural Composition in Cardiovascular Disease

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.

Keywords: blood vessels; cardiovascular diseases; myocardial infarction; thrombectomy; thrombosis.

Figure 1.

Fibrin biofilm in thrombi.A and B, Film structures in thrombi extracted from patients with abdominal aortic aneurysm. A, Fibrin film covering the thrombus (arrows). B, Film transitioning from film to fibers (arrows) and film lining channels traversing the thrombus (asterisk). C–F, Thrombi from murine thrombosis model (FeCl₃ injury of the inferior vena cava) after perfusion/fixation. C, Small thrombus showing partial film coverage (arrows). D, Film covering part of the thrombus (arrows). E and F, Film coverage localized on top of red blood cells (RBCs; arrows).

Figure 2.

Thrombus composition in myocardial infarction (MI), acute ischemic stroke (AIS), venous thrombosis (VT), and pulmonary embolism (PE). RBC indicates red blood cell. Created with BioRender.com.

Figure 3.

Ischemic time and thrombus composition in patients with ST-segment–elevation myocardial infarction (STEMI). The amounts of fibrin, polyhedrocytes, and lymphocytes increase with ischemic time, while platelet and red blood cell (RBC) loads decrease. Note: the ratios of components within each thrombus (individual graph), as well as the ratios of components between both thrombi (between graphs), are representative but not quantitative. Created with BioRender.com.