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Editorials
clot contraction compared to healthy donors,24 suggesting important associations between changes in the ability of blood clots to contract and the incidence of thromboem- bolism. These observations indicate polyhedrocytes as potential clinical markers of thromboembolism or targets for therapeutic intervention.
How the structure of the stroke thrombi in the report by Staessens et al.6 compares to other arterial or venous thrombi is another intriguing point. While arterial and venous thrombosis may be closely associated,25,26 they are triggered by different initiating mechanisms which may result in differences in the internal structure and compo- sition of the thrombi.27 Arterial thrombi occur under high shear stress, leading to platelet-rich clots that form around ruptured atherosclerotic plaques and the damaged endothelium. In contrast, venous thrombi occur under low shear stress and mostly on an intact, although likely inflamed, endothelium. Compared to arterial thrombi, venous thrombi are thought to favor the formation of clots that are fibrin-rich, encapsulating a large number of RBC in addition to activated platelets. However, despite these differences in initiating mechanisms, recent studies on structural characteristics of arterial thrombi challenge the concept that arterial thrombi are platelet-rich and venous thrombi are RBC-fibrin rich, since the arterial thrombi also contained large amounts of fibrin and RBC in addition to platelets.16,23 The current study by Staessens et al.6 also shows significant areas that are RBC- and fib- rin-rich in arterial stroke thrombi. Therefore, differences in the composition of arterial and venous thrombi are likely subtler and may not be as distinct with regards to relative fibrin, platelet and RBC contents as previously thought. Is the clot organization observed in this work for stroke thrombi also applicable to thrombi obtained from other types of thrombosis? More in-depth studies using thrombi obtained from other arterial or venous sources would help answer this very question.
The insightful imaging of thrombi from patients with stroke presented in this paper from our Belgian colleagues clearly contributes to our understanding of the cellular and molecular make-up of thrombi. It also sets an elegant example for future analysis of thrombi from other vascu- lar beds. Once more data are generated regarding the structural heterogeneity of thrombosis in both the venous and arterial circulation, we will be able to associate these findings with in vitro blood clot structure from systemic samples, providing tantalizing opportunities for new diagnostic tools. In addition, once the functional conse- quences of different thrombi structures on the behavior of these thrombi, their stability and future outcome is better documented, we should be able to improve inter- ventional and medical treatment of thrombosis, and explore theranostics or other improved personalized approaches based on the nature of the thrombus that needs to be removed.
References
1. Undas A, Ariëns RA. Fibrin clot structure and function: a role in the pathophysiology of arterial and venous thromboembolic diseases. Arterioscler Thromb Vasc Biol. 2011;31(12):e88-e99.
2. Sumaya W, Wallentin L, James SK, et al. Fibrin clot properties inde-
pendently predict adverse clinical outcome following acute coronary
syndrome: a PLATO substudy. Eur Heart J. 2018;39(13):1078-1085. 3. Siudut J, Świat M, Undas A. Altered fibrin clot properties in patients with cerebral venous sinus thrombosis: association with the risk of
recurrence. Stroke. 2015;46(9):2665-2668.
4. Weisel J, Litvinov R. Red blood cells: the forgotten player in hemo-
stasis and thrombosis. J Thromb Haemost. 2019;17(2):271-282.
5. Martinod K, Wagner DD. Thrombosis: tangled up in NETs. Blood.
2014;123(18):2768-2776.
6. Staessens S, Denorme F, François O, et al. Structural analysis of
ischemic stroke thrombi: histological indications for therapy resist-
ance. Haematologica. 2019;105(2):498-507.
7. Silvain J, Collet JP, Nagaswami C, et al. Composition of coronary
thrombus in acute myocardial infarction. J Am Coll Cardiol.
2011;57(12):1359-1367.
8. Sadowski M, Ząbczyk M, Undas A. Coronary thrombus composi-
tion: links with inflammation, platelet and endothelial markers.
Atherosclerosis. 2014;237(2):555-561.
9. RamaiolaI,PadróT,PeñaE,etal.Changesinthrombuscomposition
and profilin-1 release in acute myocardial infarction. Eur Heart J.
2014;36(16):965-975.
10. Marder VJ, Chute DJ, Starkman S, et al. Analysis of thrombi
retrieved from cerebral arteries of patients with acute ischemic
stroke. Stroke. 2006;37(8):2086-2093.
11. Simons N, Mitchell P, Dowling R, Gonzales M, Yan B. Thrombus
composition in acute ischemic stroke: a histopathological study of thrombus extracted by endovascular retrieval. J Neuroradiol. 2015;42(2):86-92.
12. Fitzgerald S, Mereuta OM, Doyle KM, et al. Correlation of imaging and histopathology of thrombi in acute ischemic stroke with etiolo- gy and outcome. J Neurosurg Sci. 2019;63(3):292-300.
13. HoshibaY,HatakeyamaK,TanabeT,AsadaY,GotoS.Co-localiza- tion of von Willebrand factor with platelet thrombi, tissue factor and platelets with fibrin, and consistent presence of inflammatory cells in coronary thrombi obtained by an aspiration device from patients with acute myocardial infarction. J Thromb Haemost. 2006;4(1):114- 120.
14. Shin JW, Jeong HS, Kwon HJ, Song KS, Kim J. High red blood cell composition in clots is associated with successful recanalization dur- ing intra-arterial thrombectomy. PloS One. 2018;13(5):e0197492.
15. TutwilerV,MukhitovAR,PeshkovaAD,etal.Shapechangesofery- throcytes during blood clot contraction and the structure of polyhe- drocytes. Sci Rep. 2018;8(1):17907.
16. Cines DB, Lebedeva T, Nagaswami C, et al. Clot contraction: com- pression of erythrocytes into tightly packed polyhedra and redistrib- ution of platelets and fibrin. Blood. 2014;123(10):1596-1603.
17. Gunning GM, McArdle K, Mirza M, Duffy S, Gilvarry M, Brouwer PA. Clot friction variation with fibrin content; implications for resist- ance to thrombectomy. J Neurointerv Surg. 2018;10(1):34-38.
18. Gersh KC, Nagaswami C, Weisel JW. Fibrin network structure and clot mechanical properties are altered by incorporation of erythro- cytes. Thromb Haemost. 2009;102(6):1169-1175.
19. De Meyer SF, Andersson T, Baxter B, et al. Analyses of thrombi in acute ischemic stroke: a consensus statement on current knowledge and future directions. Int J Stroke. 2017;12(6):606-614.
20. Staessens S, Fitzgerald S, Andersson T, et al. Histological stroke clot analysis after thrombectomy: Technical aspects and recommenda- tions. Int J Stroke. 2019:1747493019884527.
21. Gottlob R, Pötting U, Schattenmann G. [Morphologische Untersuchungen zur Frage der Retraktion, der sekundären Quellung und der Lysierbarkeit von Thromben]. Langenbeck's Archives of Surgery. 1970;327:1209-1210.
22. Ariëns RA. A new red cell shape helps the clot. Blood. 2014;123 (10):1442-1443.
23. Zalewski J, Bogaert J, Sadowski M, et al. Plasma fibrin clot pheno- type independently affects intracoronary thrombus ultrastructure in patients with acute myocardial infarction. Thromb Haemost. 2015;113(6):1258-1269.
24. PeshkovaAD,MalyasyovDV,BredikhinRA,etal.Reducedcontrac- tion of blood clots in venous thromboembolism is a potential throm- bogenic and embologenic mechanism. TH Open. 2018;2(1):e104- e115.
25. Franchini M, Mannucci PM. Association between venous and arteri- al thrombosis: clinical implications. Eur J Intern Med. 2012;23(4): 333-337.
26. Franchini M, Mannucci PM. Venous and arterial thrombosis: differ- ent sides of the same coin? Eur J Inter Med. 2008;19(7):476-481.
27. Koupenova M, Kehrel BE, Corkrey HA, Freedman JE. Thrombosis
and platelets: an update. Eur Heart J. 2016;38(11):785-791.
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