Publications · May 29, 2019

Acute ischemic stroke thrombi have an outer shell that impairs fibrinolysis

Acute ischemic stroke thrombi have an outer shell that impairs fibrinolysis

In Neurology | Volume 93, Number 18 published on May, 29th 2019

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Authors

Lucas Di Meglio, MD, Jean-Philippe Desilles, MD, PhD, Véronique Ollivier, PhD, Mialitiana Solo Nomenjanahary, MSci, Sara Di Meglio, MSci, Catherine Deschildre, MSci, Stéphane Loyau, MSci, Jean-Marc Olivot, MD, PhD, Raphael Blanc, MD, Michel Piotin, MD, Marie-Christine Bouton, PhD, Jean-Baptiste Michel, MD, PhD, Martine Jandrot-Perrus, MD, PhD, Benoit Ho-Tin-Noé, PhD, and Mikael Mazighi, MD, PhD

Abstract

Objectives

Thrombi responsible for large vessel occlusion (LVO) in the setting of acute ischemic stroke (AIS) are characterized by a low recanalization rate after IV thrombolysis. To test whether AIS thrombi have inherent common features that limit their susceptibility to thrombolysis, we analyzed the composition and ultrastructural organization of AIS thrombi causing LVO.

Methods

A total of 199 endovascular thrombectomy-retrieved thrombi were analyzed by immunohistology and scanning electron microscopy (SEM) and subjected to ex vivo thrombolysis assay. The relationship between thrombus organization and thrombolysis resistance was further investigated in vitro using thrombus produced by recalcification of citrated whole blood.

Results

SEM and immunohistology analyses revealed that, although AIS thrombus composition and organization was highly heterogeneous, AIS thrombi shared a common remarkable structural feature in the form of an outer shell made of densely compacted thrombus components including fibrin, von Willebrand factor, and aggregated platelets. In vitro thrombosis experiments using human blood indicated that platelets were essential to the formation of the thrombus outer shell. Finally, in both AIS and in vitro thrombi, the thrombus outer shell showed a decreased susceptibility to tissue plasminogen activator–mediated thrombolysis as compared to the thrombus inner core.

Interpretation

Irrespective of their etiology and despite their heterogeneity, intracranial thrombi causing LVO have a core shell structure that influences their susceptibility to thrombolysis.

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