scholarly journals Neutrophil extracellular traps and von Willebrand factor are allies that negatively influence COVID‐19 outcomes

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
María P. Fernández‐Pérez ◽  
Sonia Águila ◽  
Laura Reguilón‐Gallego ◽  
Ascensión M. los Reyes‐García ◽  
Antonia Miñano ◽  
...  
2021 ◽  
Vol 19 (1) ◽  
Author(s):  
Senna Staessens ◽  
Olivier François ◽  
Linda Desender ◽  
Peter Vanacker ◽  
Tom Dewaele ◽  
...  

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.


2014 ◽  
Vol 34 (7) ◽  
pp. 1382-1389 ◽  
Author(s):  
S. Grassle ◽  
V. Huck ◽  
K. I. Pappelbaum ◽  
C. Gorzelanny ◽  
C. Aponte-Santamaria ◽  
...  

Blood ◽  
2014 ◽  
Vol 124 (21) ◽  
pp. SCI-30-SCI-30
Author(s):  
Denisa D. Wagner

For many years, my lab has been studying the interplay between inflammation and thrombosis. These processes occur together, stimulate each other and share cellular and molecular components. The latest example of a common functional component is neutrophil extracellular traps (NETs). NETs are chromatin released together with toxic granular components from highly stimulated neutrophils. Originally found to trap/sequester invading pathogens, they were soon also seen to be part of sterile inflammatory and thrombotic processes. They interact with von Willebrand factor (VWF), which is also involved in platelet and leukocyte recruitment and is crucial for venous thrombus development after inferior vena cava stenosis. It is possible that NETs and VWF work together and cleavage of either by DNase 1 or ADAMTS13 is beneficial in ischemia/reperfusion injury. This will be discussed together with the role of NETs and the enzyme that generates them (PAD4) in animal models of deep vein thrombosis, myocardial infarction and in physiological wound healing. Interestingly, we observed that various cancers in mice prime neutrophils for NETosis. This causes cancer-associated thrombosis, and the production of NETs may affect tumor biology. Disclosures No relevant conflicts of interest to declare.


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