Histologic Characteristics of Intracranial Clots Retrieved Using Mechanical Thrombectomy

Fig. 4.1

(a) Photograph shows multiple fragmented clots having a typical appearance of red clots retrieved from a patient with acute ischemic stroke. (b) Microscopic view of a retrieved clot shows that most parts of clot consist of red blood cells in a hematoxylin-eosin stained section (×400 magnification)

White clots are mainly composed of fibrin and platelets with only a sparse amount of RBCs (Fig. 4.2). White clots are characteristically formed in fast flow circumstances, along with irregular valvular and endothelial surfaces. White clots can also be formed as a result of injury to the endothelium overlying the complicated atheromatous plaque. Clots formed at the site of underlying intracranial atherosclerotic stenosis usually consist of a fibrin network superimposed on the underlying platelet aggregates.

Fig. 4.2

(a) Photograph shows white clots retrieved with a stent retriever from a patient with acute ischemic stroke and underlying intracranial atherosclerotic stenosis. (b) Microscopic view of a retrieved clot shows that most parts of clot consist of fibrin seen as distinctly pink in a hematoxylin-eosin stained section (×400 magnification)

In vitro experimental studies support the traditional classification of clot types. For example, Duffy et al. showed that clots formed under static condition (e.g., cardiogenic thrombi) are replete with RBCs with a low fibrin composition, whereas clots formed under flow conditions are fibrin-rich [5]. Under static conditions (stationary coagulation of whole blood), the mean % areas in the resulting clots were 91% RBCs, 8% fibrin, and 0.98% white blood cells (WBCs). In contrast, under flow conditions mimicking the carotid blood flow rates (approximately 240 mL/min), the mean % areas in the resulting clots were 18% RBCs, 79% fibrin, and 2.7% WBCs [5].

4.2 Histologic Analysis of Retrieved Clots

A mechanical thrombectomy is currently the first-line endovascular therapy for patients with acute large-vessel occlusions [1]. Recent studies have shown that a mechanical thrombectomy using a retrievable stent or flexible aspiration catheter is associated with a high recanalization rate and low complication rate [2, 3]. Furthermore, the use of a mechanical thrombectomy for acute stroke treatment facilitates the histopathologic examination of clots retrieved from intracranial arteries, providing new insights into the pathogenesis of acute stroke due to an intracranial large-vessel occlusion, along with an understanding of the pathologic basis of early vessel signs on imaging studies in patients with acute ischemic stroke.

Previous studies have demonstrated that the histologic composition of clots retrieved from patients with acute ischemic stroke is typically RBC-dominant (Fig. 4.3), fibrin-dominant (Fig. 4.4), or mixed [6–9]. Liebeskind et al. conducted a histopathologic analysis of clots retrieved from 50 patients with acute anterior circulation stroke and reported that 44% of the clots were fibrin-dominant, 26% were RBC-dominant, and 30% were mixed [8]. Meanwhile, Boeckh-Behrens et al. analyzed clots retrieved from 34 patients with acute anterior circulation stroke and reported that 50% of the clots were fibrin-dominant (>60% of fibrin), 12% were RBC-dominant (>60% of RBC), and 38% were mixed [9]. To date, the histopathologic studies of retrieved clots have mainly focused on the following: (1) the relationship between the histologic composition of clots and the stroke etiology and (2) the relationship between the histologic composition of clots and the imaging characteristics.

Fig. 4.3

Brain images from an 86-year-old woman with acute MCA occlusion and atrial fibrillation. (a) Axial gradient-echo MR image reveals a positive susceptibility vessel sign (arrow) in the M1 segment of the left MCA. (b) 3D TOF MR angiography shows the occlusion in the proximal M1 segment of the left MCA. (c) Microscopic view of a retrieved clot shows that most of the thrombi consist of red blood cells in a hematoxylin-eosin stained section (×100 magnification). (d) CD 61 immunostained section shows small areas of platelet infiltration (brown) in the periphery of the clot (×100 magnification)

Fig. 4.4

Brain images from a 74-year-old man with acute MCA occlusion and underlying intracranial atherosclerotic stenosis. (a) Axial gradient-echo MR image reveals a negative susceptibility vessel sign (arrow) in the M1 segment of the right MCA. (b) 3D TOF MR angiography shows the occlusion in the proximal M1 segment of the right MCA. (c) Microscopic view of a retrieved clot shows that most of the thrombi consist of organized fibrin aggregates with sparse cellular elements in a hematoxylin-eosin stained section (×100 magnification). (d) CD 61 immunostained section shows abundant infiltrations of platelets (brown) in the central and peripheral portion of the clot (×100 magnification)

4.3 Clot Compositions and Stroke Etiology

A clot composition analysis can potentially reveal important information regarding the stroke etiology, helping physicians to make a strategy for secondary stroke prevention. However, it remains unclear whether clot composition analysis can be used to predict a stroke mechanism in the case of an acute large-vessel occlusion. As yet, only a few studies have focused on this topic and yielded vague and contradictory results due to differences in the histologic staining methods, quantification methods, and component assignment [6–9].

Kim et al. suggested that the histologic composition of clots retrieved from cerebral arteries in the case of acute anterior circulation stroke differed between patients with a cardioembolism and patients with large-artery atherosclerosis [6]. In a semiquantitative proportion analysis to quantify the RBC, fibrin, platelets, and WBC by area after staining, the clot tissue with hematoxylin-eosin and antibodies for platelet glycoprotein IIIa, CD 61, the RBC, and fibrin percentages differed significantly between the patients with a cardioembolism and the patients with large-artery atherosclerosis, where the former had a significantly higher proportion of RBCs and lower proportion of fibrin than the latter (Figs. 4.3 and 4.4). No significant differences were found in the proportions of platelets and WBCs between the patients with a cardioembolism and the patients with large-artery atherosclerosis. Thus, Kim’s study supports the concept that, in an acute ischemic stroke setting, cardioembolic thrombi forming in regions of blood stasis or slow flow are mainly composed of entrapped RBCs while thrombi occurring in the context of atherosclerotic large arteries are mainly composed of fibrin and platelets. Kim’s findings also match the results of a postmortem study by Sato et al., which examined the cerebral arteries and thrombi of 17 patients who died of cardioembolic (n = 11) and large-artery atherosclerotic (n = 6) strokes within 30 days of stroke onset [10]. Similarly, Sato el al. found that the ratio and total area of RBCs were significantly larger in the cardioembolic thrombi than in the large-artery atherosclerotic thrombi, while the ratio of fibrin was threefold higher in the large-artery atherosclerotic thrombi than in the cardioembolic thrombi [10].

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