Thrombus Composition in Cerebral Venous Thrombosis

Abstract

Background and Aims: Histological analysis of thrombi can enhance the understanding of pathophysiology. We aimed to analyze EVT-retrieved thrombi in cerebral venous thrombosis (CVT), compare them with acute ischemic stroke (AIS) thrombi, and correlate their composition with CT density. Methods: Retrospective case-series, including five CVT and 10 AIS cases treated with EVT. Thrombus sections were stained with hematoxylin and eosin; Picro Mallory for RBCs, fibrin, and collagen; and Prussian Blue for iron plus immunohistochemical staining with anti-CD61 (platelets), anti-MPO (neutrophils), anti-CD3 (T-cells), anti-CD20 (B-cells), anti-CD34 (endothelial cells), anti-CD68 (macrophages), and anti-citH3 (NETs). Thrombus components were quantified (Orbit) and expressed as a percentage of total area. The CVT-thrombus relative density (rHU) was calculated as HU thrombus/HU contralateral. Results: All CVT cases showed extensive thrombosis. Four patients had prior anticoagulation, and four had rHU > 1.00 with CT hyperdensity. The etiologies were heterogeneous. CVT thrombi were rich in red blood cells and displayed variable histological features, including signs of early organization. Compared to arterial thrombi, venous thrombi exhibited larger size (surface area 185.6 mm² [IQR 83.0-237.9] vs. 21.8 mm² [IQR 8.8-77.8]; p = 0.028) and lower fibrin content (16.6% [IQR 13.9-31.5] vs. 46.5% [IQR 25.1-49.5]; p = 0.036), with no other significant differences in composition. Low fibrin content and high RBC-to-fibrin ratio (R -0.9 and R 0.9, respectively; p = 0.047 for both) showed a significant correlation with rHU. Conclusion: Our exploratory study first shows that CVT thrombi are larger than AIS thrombi, with higher RBC content and lower fibrin, matching CT density. These findings enhance the understanding of CVT pathophysiology but need validation.

Figure 1

Thrombus assessment and composition of CVT- and AIS-related thrombi. (a) Venous thrombi (CVT) were significantly larger than arterial thrombi (AIS) (p = 0.028), as illustrated by both the bar chart and low-magnification H&E-stained sections. Picro Mallory staining shows that (b) red blood cell content (yellow) was comparable between groups (p = 0.729), (c) fibrin (pink/purple) was significantly lower in CVT thrombi (p = 0.036), and (d) collagen content (blue) did not differ significantly (p = 0.129). Immunohistochemistry demonstrated similar levels of (e) platelets (CD61+, p = 0.390) and (f) neutrophils (MPO+, p = 0.548) in venous and arterial thrombi. (g) NET content (CitH3+) was comparable between groups (p = 0.679). No significant differences were observed in (h) macrophage (CD68+, p = 0.514), (i) T-cell (CD3+, p = 0.440), or (j) B-cell (CD20+, p = 0.324) infiltration. (k) Endothelial cells (CD34+) were more abundant in CVT thrombi, though not significantly (p = 0.310). (l) Iron deposits, assessed via Prussian blue staining, were minimal and comparable across groups (p = 0.953).