Per-pass analysis of acute ischemic stroke clots: impact of stroke etiology on extracted clot area and histological composition

Abstract

Background: Initial studies investigating correlations between stroke etiology and clot composition are conflicting and do not account for clot size as determined by area. Radiological studies have shown that cardioembolic strokes are associated with shorter clot lengths and lower clot burden than non-cardioembolic clots.

Objective: To report the relationship between stroke etiology, extracted clot area, and histological composition at each procedural pass.

Methods: As part of the multi-institutional RESTORE Registry, the Martius Scarlett Blue stained histological composition and extracted clot area of 612 per-pass clots retrieved from 441 patients during mechanical thrombectomy procedures were quantified. Correlations with clinical and procedural details were investigated.

Results: Clot composition varied significantly with procedural passes; clots retrieved in earlier passes had higher red blood cell content (H4=11.644, p=0.020) and larger extracted clot area (H4=10.730, p=0.030). Later passes were associated with significantly higher fibrin (H4=12.935, p=0.012) and platelets/other (H4=15.977, p=0.003) content and smaller extracted clot area. Large artery atherosclerotic (LAA) clots were significantly larger in the extracted clot area and more red blood cell-rich than other etiologies in passes 1-3. Cardioembolic and cryptogenic clots had similar histological composition and extracted clot area across all procedural passes.

Conclusion: LAA clots are larger and associated with a large red blood cell-rich extracted clot area, suggesting soft thrombus material. Cardioembolic clots are smaller in the extracted clot area, consistent in composition and area across passes, and have higher fibrin and platelets/other content than LAA clots, making them stiffer clots. The per-pass histological composition and extracted clot area of cryptogenic clots are similar to those of cardioembolic clots, suggesting similar formation mechanisms.

Keywords: atherosclerosis; intervention; stroke; thrombectomy.

Figure 1

Histological clot composition and extracted clot area per histological component. (A) Mean histological clot composition (%) of each procedural pass, as determined by MSB staining represented as the percentage of the total. (B) The mean area of each histological component within a procedural pass is calculated by multiplying each component’s histological composition by the extracted clot area of the corresponding procedural pass. (C) Mean histological clot composition (%) of each suspected etiology. (D) Mean area of each histological component within each suspected etiology. ECA, extracted clot area; LAA, large artery atherosclerotic (clots); MSB, Martius Scarlett Blue; RBCs, red blood cells; WBCs, white blood cells.

Figure 2

Gross photographs, MSB staining and per-pass extracted clot area of each histological component per suspected etiology. (A–C) Graphical representation of the per-pass histological composition multiplied by the extracted clot area of each suspected etiology; (A) LAA, (B) cardioembolic, and (C) cryptogenic. (D–F) Gross photographs used for extracted clot area quantification of the clots removed in passes 1 and 2 of each suspected etiology; (D) LAA, (E) cardioembolic, and (F) cryptogenic. (G–I) Corresponding MSB-stained slides used for histological quantification. *Red blood cells area in passes 1–3 of LAA clots was significantly larger than later LAA passes and all clot per pass for cardioembolic and cryptogenic etiologies. LAA, large artery atherosclerotic (clots); MSB, Martius Scarlett Blue.