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Acute ischemic stroke thrombi have an outer shell that impairs fibrinolysis
- Source :
- Neurology, Neurology, American Academy of Neurology, 2019, 93 (18), pp.e1686-e1698. ⟨10.1212/WNL.0000000000008395⟩, Neurology, 2019, 93 (18), pp.e1686-e1698. ⟨10.1212/WNL.0000000000008395⟩
- Publication Year :
- 2019
-
Abstract
- ObjectivesThrombi 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.MethodsA 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.ResultsSEM 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.InterpretationIrrespective of their etiology and despite their heterogeneity, intracranial thrombi causing LVO have a core shell structure that influences their susceptibility to thrombolysis.
- Subjects :
- Male
Pathology
Erythrocytes
medicine.medical_treatment
[SDV.NEU.NB]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC]/Neurobiology
Drug Resistance
030204 cardiovascular system & hematology
Extracellular Traps
[SDV.IMM.II]Life Sciences [q-bio]/Immunology/Innate immunity
Brain Ischemia
0302 clinical medicine
Leukocytes
Thrombolytic Therapy
Platelet
030212 general & internal medicine
Acute ischemic stroke
Thrombectomy
Whole blood
Aged, 80 and over
[SDV.MHEP] Life Sciences [q-bio]/Human health and pathology
biology
Search Terms: Stroke
Thrombolysis
Middle Aged
Immunohistochemistry
Thrombosis
[SDV.MHEP.CSC] Life Sciences [q-bio]/Human health and pathology/Cardiology and cardiovascular system
Stroke
Tissue Plasminogen Activator
Cardiology
cardiovascular system
Female
circulatory and respiratory physiology
Blood Platelets
medicine.medical_specialty
thrombolysis
Shell (structure)
[SDV.CAN]Life Sciences [q-bio]/Cancer
In Vitro Techniques
Fibrin
Article
03 medical and health sciences
[SDV.CAN] Life Sciences [q-bio]/Cancer
Fibrinolytic Agents
Von Willebrand factor
[SDV.MHEP.CSC]Life Sciences [q-bio]/Human health and pathology/Cardiology and cardiovascular system
Internal medicine
von Willebrand Factor
Fibrinolysis
medicine
Humans
shell Publication history: none Submission Type: Article Title character count: 75 Number of Tables : 1 + 1 supplemental
cardiovascular diseases
Thrombus
[SDV.IMM.II] Life Sciences [q-bio]/Immunology/Innate immunity
Aged
business.industry
[SDV.NEU.NB] Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC]/Neurobiology
Correction
medicine.disease
Microscopy, Electron, Scanning
biology.protein
thrombus histology
Neurology (clinical)
Intracranial Thrombosis
business
030217 neurology & neurosurgery
thrombus structure
[SDV.MHEP]Life Sciences [q-bio]/Human health and pathology
Subjects
Details
- ISSN :
- 1526632X and 00283878
- Volume :
- 93
- Issue :
- 18
- Database :
- OpenAIRE
- Journal :
- Neurology
- Accession number :
- edsair.doi.dedup.....97fc22f7679a8501317a993888938776