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Article ; Online: Mechanical thrombectomy for acute ischemic stroke revealing a cardiac myxoma: histological and immunohistochemical study to determine myxomatous emboli.

Vantyghem, Soetkin / Staessens, Senna / Francois, Olivier / De Meyer, Simon F / Vanacker, Peter

2023 Volume 123, Issue 3, Page(s) 1201–1203

MeSH term(s)	Humans ; Ischemic Stroke/complications ; Ischemic Stroke/diagnostic imaging ; Stroke/complications ; Stroke/diagnostic imaging ; Brain Ischemia/complications ; Brain Ischemia/diagnostic imaging ; Thrombectomy ; Myxoma/complications ; Myxoma/diagnostic imaging ; Myxoma/pathology ; Tissue Plasminogen Activator ; Treatment Outcome
Chemical Substances	Tissue Plasminogen Activator (EC 3.4.21.68)
Language	English
Publishing date	2023-04-11
Publishing country	Italy
Document type	Letter
ZDB-ID	127315-2
ISSN	2240-2993 ; 0300-9009
ISSN (online)	2240-2993
ISSN	0300-9009
DOI	10.1007/s13760-023-02254-6
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Article ; Online: Thrombus heterogeneity in ischemic stroke.

Staessens, Senna / De Meyer, Simon F

Platelets

2020 Volume 32, Issue 3, Page(s) 331–339

Abstract: The structure of stroke thrombi has gained an increasing amount of interest in recent years. The advent of endovascular thrombectomy has offered the unique opportunity to provide and analyze thrombi removed from ischemic stroke patients. It has become ... ...

Abstract	The structure of stroke thrombi has gained an increasing amount of interest in recent years. The advent of endovascular thrombectomy has offered the unique opportunity to provide and analyze thrombi removed from ischemic stroke patients. It has become clear that the composition of ischemic stroke thrombi is relatively heterogenous and various molecular and cellular patterns become apparent. Good understanding of the histopathologic characteristics of thrombi is important to lead future advancements in acute ischemic stroke treatment. In this review, we give a brief overview of the main stroke thrombus components that have been recently characterized in this rapidly evolving field. We also summarize how thrombus heterogeneity can affect stroke treatment.
MeSH term(s)	Female ; Genetic Heterogeneity ; Humans ; Ischemic Stroke/complications ; Ischemic Stroke/genetics ; Ischemic Stroke/pathology ; Male ; Thrombectomy/methods ; Thrombosis/genetics
Language	English
Publishing date	2020-04-20
Publishing country	England
Document type	Journal Article ; Review
ZDB-ID	1034283-7
ISSN	1369-1635 ; 0953-7104
ISSN (online)	1369-1635
ISSN	0953-7104
DOI	10.1080/09537104.2020.1748586
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Article ; Online: R-tPA Resistance Is Specific for Platelet-Rich Stroke Thrombi and Can Be Overcome by Targeting Nonfibrin Components.

Vandelanotte, Sarah / François, Olivier / Desender, Linda / Staessens, Senna / Vanhoorne, Alexander / Van Gool, Fréderick / Tersteeg, Claudia / Vanhoorelbeke, Karen / Vanacker, Peter / Andersson, Tommy / De Meyer, Simon F

Stroke

2024 Volume 55, Issue 5, Page(s) 1181–1190

Abstract: Background: Resistance to r-tPA (recombinant tissue-type plasminogen activator) is a well-known but poorly understood phenomenon that hampers successful recanalization in patients with acute ischemic stroke. Using clinically relevant thrombi from ... ...

Abstract	Background: Resistance to r-tPA (recombinant tissue-type plasminogen activator) is a well-known but poorly understood phenomenon that hampers successful recanalization in patients with acute ischemic stroke. Using clinically relevant thrombi from patients with acute ischemic stroke, we investigated if and how thrombus composition impacts r-tPA-mediated lysis. In addition, we explored strategies to overcome r-tPA resistance. Methods: Thrombi were split into 2 parts, 1 of which was used for thrombolysis and the other for detailed histological analysis. Thrombolysis was performed in normal human plasma using r-tPA alone, using r-tPA in combination with DNase-1 or using r-tPA in combination with N,N'-diacetyl-l-cystine. Thrombus lysis was calculated as the percentage of residual thrombus weight compared with its initial weight and the degree of lysis was linked to thrombus composition determined via histology. Results: Interestingly, we found that the efficacy of r-tPA-mediated thrombolysis was strongly correlated with the composition of the thrombi. Thrombi containing high amounts of red blood cells and low amounts of DNA and von Willebrand Factor were efficiently degraded by r-tPA, whereas thrombi containing low amounts of red blood cells and higher amounts of DNA and von Willebrand Factor were resistant to r-tPA. Importantly, combination of r-tPA with DNase-1 or N,N'-diacetyl-l-cystine significantly and specifically improved the lysis of these r-tPA-resistant thrombi. Conclusions: Using patient thrombus material, our results for the first time show that the composition of stroke thrombi largely determines their susceptibility to r-tPA-mediated thrombolysis. Red blood cell-poor thrombi have a specific resistance to r-tPA, which can be overcome by targeting nonfibrin components using DNase-1 or N,N'-diacetyl-l-cystine.
Language	English
Publishing date	2024-03-25
Publishing country	United States
Document type	Journal Article
ZDB-ID	80381-9
ISSN	1524-4628 ; 0039-2499 ; 0749-7954
ISSN (online)	1524-4628
ISSN	0039-2499 ; 0749-7954
DOI	10.1161/STROKEAHA.123.045880
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Article: Detailed histological analysis of a thrombectomy-resistant ischemic stroke thrombus: a case report.

Staessens, Senna / François, Olivier / Desender, Linda / Vanacker, Peter / Dewaele, Tom / Sciot, Raf / Vanhoorelbeke, Karen / Andersson, Tommy / De Meyer, Simon F

Thrombosis journal

2021 Volume 19, Issue 1, Page(s) 11

Abstract: Background: Mechanical removal of a thrombus by thrombectomy can be quite challenging. For reasons that are not fully understood, some thrombi require multiple passes to achieve successful recanalization, whereas other thrombi are efficiently removed in ...

Abstract	Background: Mechanical removal of a thrombus by thrombectomy can be quite challenging. For reasons that are not fully understood, some thrombi require multiple passes to achieve successful recanalization, whereas other thrombi are efficiently removed in a single pass. Since first pass success is associated with better clinical outcome, it is important to better understand the nature of thrombectomy resistant thrombi. The aim of this study was therefore to characterize the cellular and molecular composition of a thrombus that was very hard to retrieve via mechanical thrombectomy. Case presentation: In a patient that was admitted with a right middle cerebral artery M1-occlusion, 11 attempts using various thrombectomy devices and techniques were required for removal of the thrombus. This peculiar case provided a rare opportunity to perform an in-depth histopathological study of a difficult to retrieve thrombus. Thrombus material was histologically analyzed using hematoxylin and eosin, Martius Scarlet Blue stain (red blood cells and fibrin), Feulgen stain (DNA), von Kossa stain (calcifications) and immunohistochemical analysis of von Willebrand factor, platelets, leukocytes and neutrophil extracellular traps. Histological analysis revealed abnormally high amounts of extracellular DNA, leukocytes, von Willebrand factor and calcifications. Extracellular DNA stained positive for markers of leukocytes and NETs, suggesting that a significant portion of DNA is derived from neutrophil extracellular traps. Conclusion: In this unique case of a nearly thrombectomy-resistant stroke thrombus, our study showed an atypical composition compared to the common structural features found in ischemic stroke thrombi. The core of the retrieved thrombus consisted of extracellular DNA that colocalized with von Willebrand factor and microcalcifications. These results support the hypothesis that von Willebrand factor, neutrophil extracellular traps and microcalcifications contribute to mechanical thrombectomy resistance. Such information is important to identify novel targets in order to optimize technical treatment protocols and techniques to increase first pass success rates.
Language	English
Publishing date	2021-02-22
Publishing country	England
Document type	Journal Article
ISSN	1477-9560
ISSN	1477-9560
DOI	10.1186/s12959-021-00262-1
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Article ; Online: Studying Stroke Thrombus Composition After Thrombectomy: What Can We Learn?

Staessens, Senna / François, Olivier / Brinjikji, Waleed / Doyle, Karen M / Vanacker, Peter / Andersson, Tommy / De Meyer, Simon F

Stroke

2021 Volume 52, Issue 11, Page(s) 3718–3727

Abstract: The composition of ischemic stroke thrombi has gained an increasing amount of interest in recent years. The implementation of endovascular procedures in standard stroke care has granted researchers the unique opportunity to examine patient thrombus ... ...

Abstract	The composition of ischemic stroke thrombi has gained an increasing amount of interest in recent years. The implementation of endovascular procedures in standard stroke care has granted researchers the unique opportunity to examine patient thrombus material. Increasing evidence indicates that stroke thrombi are complex and heterogenous, consisting of various biochemical (eg, fibrin, von Willebrand Factor, and neutrophil extracellular traps) and cellular (eg, red blood cells, platelets, leukocytes, and bacteria) components. This complex composition may explain therapeutic limitations and also offer novel insights in several aspects of stroke management. Better understanding of thrombus characteristics could, therefore, potentially lead to improvements in the management of patients with stroke. In this review, we provide a comprehensive overview of the lessons learned by examining stroke thrombus composition after endovascular thrombectomy and its potential relevance for thrombectomy success rates, thrombolysis, clinical outcomes, stroke etiology, and radiological imaging.
MeSH term(s)	Humans ; Ischemic Stroke ; Thrombectomy ; Thrombosis
Language	English
Publishing date	2021-09-14
Publishing country	United States
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't ; Review
ZDB-ID	80381-9
ISSN	1524-4628 ; 0039-2499 ; 0749-7954
ISSN (online)	1524-4628
ISSN	0039-2499 ; 0749-7954
DOI	10.1161/STROKEAHA.121.034289
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Article: Unusual Histopathological Findings in Mechanically Removed Stroke Thrombi - A Multicenter Experience.

Aspegren, Oskar / Staessens, Senna / Vandelanotte, Sarah / Desender, Linda / Cordonnier, Charlotte / Puy, Laurent / Bricout, Nicolas / De Meyer, Simon F / Andersson, Tommy / Arnberg, Fabian

Frontiers in neurology

2022 Volume 13, Page(s) 846293

Abstract: Background: Several studies have investigated the histopathology of mechanically retrieved thrombi from stroke patients. Thrombi with unusual components constitute about 1-2% of all stroke thrombi in clinical practice. Knowledge about these rare ... ...

Abstract	Background: Several studies have investigated the histopathology of mechanically retrieved thrombi from stroke patients. Thrombi with unusual components constitute about 1-2% of all stroke thrombi in clinical practice. Knowledge about these rare components is limited. Objectives: To characterize the histopathology of unusual stroke thrombi from a real-world setting with relation to clinical presentation, patient characteristics and procedural aspects of mechanical thrombectomy. Methods: One-thousand and eight thrombi retrieved from stroke patients with mechanical thrombectomy at three different hospitals were retrospectively reviewed for unusual histological components. Fifteen thrombi were included in the study for further histopathological analysis. Clinical data and data on procedural aspects were collected. Results: We identified six cases with large amounts of extracellular DNA, of which three were calcified. All six cases except one received anticoagulant therapy. We describe two types of calcifications that differ with respect to general calcification morphology, von Kossa staining pattern, macrophage immunophenotype and presence of multinucleated giant cells. Cholesterol-rich ( Conclusion: In our retrospective multicenter study, we characterized stroke thrombi histopathologically and found subgroups of thrombi defined by presence of rarely seen components. These defined subgroups showed relation to underlying cardiovascular disease, patient characteristics, and mechanical thrombectomy technique. Knowledge about these components may increase our understanding of stroke pathophysiology and influence interventional procedures.
Language	English
Publishing date	2022-05-17
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	2564214-5
ISSN	1664-2295
ISSN	1664-2295
DOI	10.3389/fneur.2022.846293
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Article ; Online: Identifying ex vivo acute ischemic stroke thrombus composition using electrochemical impedance spectroscopy.

Interventional neuroradiology : journal of peritherapeutic neuroradiology, surgical procedures and related neurosciences

2023 , Page(s) 15910199231175377

Abstract: Background: Intra-procedural characterization of stroke thromboemboli might guide mechanical thrombectomy (MT) device choice to improve recanalization rates. Electrochemical impedance spectroscopy (EIS) has been used to characterize various biological ... ...

Abstract	Background: Intra-procedural characterization of stroke thromboemboli might guide mechanical thrombectomy (MT) device choice to improve recanalization rates. Electrochemical impedance spectroscopy (EIS) has been used to characterize various biological tissues in real time but has not been used in thrombus. Objective: To perform a feasibility study of EIS analysis of thrombi retrieved by MT to evaluate: (1) the ability of EIS and machine learning to predict red blood cell (RBC) percentage content of thrombi and (2) to classify the thrombi as "RBC-rich" or "RBC-poor" based on a range of cutoff values of RBC. Methods: ClotbasePilot was a multicentric, international, prospective feasibility study. Retrieved thrombi underwent histological analysis to identify proportions of RBC and other components. EIS results were analyzed with machine learning. Linear regression was used to evaluate the correlation between the histology and EIS. Sensitivity and specificity of the model to classify the thrombus as RBC-rich or RBC-poor were also evaluated. Results: Among 514 MT,179 thrombi were included for EIS and histological analysis. The mean composition in RBC of the thrombi was 36% ± 24. Good correlation between the impedance-based prediction and histology was achieved (slope of 0.9, Conclusion: Combination of EIS and machine learning can reliably predict the RBC composition of retrieved ex vivo AIS thrombi and then classify them into groups according to their RBC composition with good sensitivity and specificity.
Language	English
Publishing date	2023-05-16
Publishing country	United States
Document type	Journal Article
ZDB-ID	1354913-3
ISSN	2385-2011 ; 1591-0199 ; 1123-9344
ISSN (online)	2385-2011
ISSN	1591-0199 ; 1123-9344
DOI	10.1177/15910199231175377
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Article ; Online: Structural analysis of ischemic stroke thrombi: histological indications for therapy resistance.

Staessens, Senna / Denorme, Frederik / Francois, Olivier / Desender, Linda / Dewaele, Tom / Vanacker, Peter / Deckmyn, Hans / Vanhoorelbeke, Karen / Andersson, Tommy / De Meyer, Simon F

Haematologica

2020 Volume 105, Issue 2, Page(s) 498–507

Abstract: Ischemic stroke is caused by a thromboembolic occlusion of cerebral arteries. Treatment is focused on fast and efficient removal of the occluding thrombus, ... ...

Abstract	Ischemic stroke is caused by a thromboembolic occlusion of cerebral arteries. Treatment is focused on fast and efficient removal of the occluding thrombus, either
MeSH term(s)	Brain Ischemia/therapy ; Humans ; Ischemic Stroke ; Stroke/therapy ; Thrombectomy ; Thrombosis/etiology ; Thrombosis/therapy
Language	English
Publishing date	2020-01-31
Publishing country	Italy
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	2333-4
ISSN	1592-8721 ; 0017-6567 ; 0390-6078
ISSN (online)	1592-8721
ISSN	0017-6567 ; 0390-6078
DOI	10.3324/haematol.2019.219881
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Article ; Online: Thrombus formation during ECMO: Insights from a detailed histological analysis of thrombus composition.

Journal of thrombosis and haemostasis : JTH

2022 Volume 20, Issue 9, Page(s) 2058–2069

Abstract: Objectives: Intra-device thrombosis remains one of the most common complications during extracorporeal membrane oxygenation (ECMO). Despite anticoagulation, approximately 35% of patients develop thrombi in the membrane oxygenator, pump heads, or tubing. ...

Abstract	Objectives: Intra-device thrombosis remains one of the most common complications during extracorporeal membrane oxygenation (ECMO). Despite anticoagulation, approximately 35% of patients develop thrombi in the membrane oxygenator, pump heads, or tubing. The aim of this study was to describe the molecular and cellular features of ECMO thrombi and to study the main drivers of thrombus formation at different sites in the ECMO circuits. Approach and results: Thrombi (n = 85) were collected immediately after veno-arterial-(VA)-ECMO circuit removal from 25 patients: 23 thrombi from the pump, 25 from the oxygenator, and 37 from the tubing. Quantitative histological analysis was performed for the amount of red blood cells (RBCs), platelets, fibrin, von Willebrand factor (VWF), leukocytes, and citrullinated histone H3 (H3Cit). ECMO thrombi consist of a heterogenous composition with fibrin and VWF being the major thrombus components. A clustering analysis of the four major histological parameters identified two typical thrombus types: RBC-rich and RBC-poor/fibrin-rich thrombi with no significant differences in VWF and platelet content. Thrombus composition was not associated with the thrombus location, except for higher amounts of H3Cit that were found in pump and oxygenator thrombi compared to tubing samples. We observed higher blood leukocyte count and lactate dehydrogenase levels in patients with fibrin-rich thrombi. Conclusion: We found that thrombus composition is heterogenous, independent of their location, consisting of two types: RBC-rich and a fibrin-rich types. We also found that NETs play a minor role. These findings are important to improve current anticoagulation strategies in ECMO.
MeSH term(s)	Anticoagulants ; Extracorporeal Membrane Oxygenation/adverse effects ; Fibrin/analysis ; Humans ; Thrombosis ; von Willebrand Factor
Chemical Substances	Anticoagulants ; von Willebrand Factor ; Fibrin (9001-31-4)
Language	English
Publishing date	2022-07-03
Publishing country	England
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	2112661-6
ISSN	1538-7836 ; 1538-7933
ISSN (online)	1538-7836
ISSN	1538-7933
DOI	10.1111/jth.15784
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Article ; Online: Vascular Endothelial Damage in the Pathogenesis of Organ Injury in Severe COVID-19.

Dupont, Annabelle / Rauch, Antoine / Staessens, Senna / Moussa, Mouhamed / Rosa, Mickael / Corseaux, Delphine / Jeanpierre, Emmanuelle / Goutay, Julien / Caplan, Morgan / Varlet, Pauline / Lefevre, Guillaume / Lassalle, Fanny / Bauters, Anne / Faure, Karine / Lambert, Marc / Duhamel, Alain / Labreuche, Julien / Garrigue, Delphine / De Meyer, Simon F /

Staels, Bart / Vincent, Flavien / Rousse, Natacha / Kipnis, Eric / Lenting, Peter / Poissy, Julien / Susen, Sophie

Arteriosclerosis, thrombosis, and vascular biology

2021 Volume 41, Issue 5, Page(s) 1760–1773

Abstract: Figure: see text]. ...

Abstract	[Figure: see text].
MeSH term(s)	Biomarkers/blood ; COVID-19/complications ; COVID-19/immunology ; COVID-19/pathology ; Complement Activation ; Critical Care ; Cytokines/blood ; Endothelium, Vascular/pathology ; Female ; Humans ; Liver Failure, Acute/virology ; Male ; Microcirculation ; Middle Aged ; Multiple Organ Failure/virology ; Nucleosomes/metabolism ; Respiratory Insufficiency/virology ; SARS-CoV-2 ; Thrombosis/virology
Chemical Substances	Biomarkers ; Cytokines ; Nucleosomes
Language	English
Publishing date	2021-02-25
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	1221433-4
ISSN	1524-4636 ; 1079-5642
ISSN (online)	1524-4636
ISSN	1079-5642
DOI	10.1161/ATVBAHA.120.315595
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