Acute ischemic stroke thrombi have an outer shell that impairs fibrinolysis.
Aged
Aged, 80 and over
Blood Platelets
/ metabolism
Brain Ischemia
/ drug therapy
Drug Resistance
Erythrocytes
/ metabolism
Extracellular Traps
/ metabolism
Female
Fibrin
/ metabolism
Fibrinolytic Agents
/ therapeutic use
Humans
Immunohistochemistry
In Vitro Techniques
Intracranial Thrombosis
/ drug therapy
Leukocytes
/ metabolism
Male
Microscopy, Electron, Scanning
Middle Aged
Stroke
/ drug therapy
Thrombectomy
Thrombolytic Therapy
Tissue Plasminogen Activator
/ therapeutic use
von Willebrand Factor
/ metabolism
Journal
Neurology
ISSN: 1526-632X
Titre abrégé: Neurology
Pays: United States
ID NLM: 0401060
Informations de publication
Date de publication:
29 10 2019
29 10 2019
Historique:
received:
25
01
2019
accepted:
29
05
2019
pubmed:
22
9
2019
medline:
6
2
2020
entrez:
22
9
2019
Statut:
ppublish
Résumé
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. 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. 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 Irrespective of their etiology and despite their heterogeneity, intracranial thrombi causing LVO have a core shell structure that influences their susceptibility to thrombolysis.
Identifiants
pubmed: 31541014
pii: WNL.0000000000008395
doi: 10.1212/WNL.0000000000008395
pmc: PMC6946479
doi:
Substances chimiques
Fibrinolytic Agents
0
von Willebrand Factor
0
Fibrin
9001-31-4
Tissue Plasminogen Activator
EC 3.4.21.68
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
e1686-e1698Commentaires et corrections
Type : ErratumIn
Informations de copyright
© 2019 American Academy of Neurology.
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