Pathophysiologic and Therapeutic Perspectives Based on Thrombus Histology in Stroke

Abstract

Recent advances in endovascular thrombectomy have enabled the histopathologic analysis of fresh thrombi in patients with acute stroke. Histologic analysis has shown that the thrombus composition is very heterogeneous between patients. However, the distribution pattern of each thrombus component often differs between patients with cardiac thrombi and those with arterial thrombi, and the efficacy of endovascular thrombectomy is different according to the thrombus composition. Furthermore, the thrombus age is related to the efficacy of reperfusion therapy. Recent studies have shown that neutrophils and neutrophil extracellular traps contribute to thrombus formation and resistance to reperfusion therapy. Histologic features of thrombi in patients with stroke may provide some clues to stroke etiology, which is helpful for determining the strategy of stroke prevention. Research on thrombus may also be helpful for improving reperfusion therapy, including the development of new thrombolytic agents.

Keywords: Histology; Intracranial thrombus; Stroke; Thrombectomy.

Figure 1.

An illustration showing the process of neutrophil extracellular trap (NET) formation. NETs are formed within activated neutrophils, and then released from neutrophils. Released NETs form a web-like structure, which plays a role as a scaffold of thrombus. NETs also actively interact with platelets and erythrocytes to form thrombus.

Figure 2.

Representative immunohistochemistry images of the human thrombus outlining (A) neutrophils (anti-myeloperoxidase) and (B) neutrophil extracellular traps (anti-histone H3). Areas expressing neutrophils are overlapped with those expressing neutrophil extracellular traps. Positive signals to primary antibodies were developed using 3,3ʹ-diaminobenzidine, and are seen as areas of brown staining (×400).

Figure 3.

Variable features of neutrophil extracellular traps. Immunoreactivity to histone H3 (brown staining), representing neutrophil extracellular traps, is seen as (A) cell-like (within cells), (B) filopodia-like, or (C) web-like features. Lower panels are magnifications of the upper panel images (×400).

Figure 4.

(A, B, C) Representative immunohistochemistry images of the human thrombus outlining platelets (anti-CD42b), erythrocytes (anti-glycophorin A), and fibrin/fibrinogen (anti-fibrinogen) in a patient with atrial fibrillation (AF) and large artery atherosclerosis (LAA). The staining in the patient with AF shows a layered pattern of clustered platelets, whereas that in the patient with LAA shows peripherally located platelets and a large erythrocyte mass (×400).