Keywords
Thrombectomy
Cerebral artery thrombus
Pathology
Submitted : 2024-11-27
Accepted : 2024-12-12
Published : 2024-12-27
Abstract
Acute cerebral infarction, with a high incidence, disability, and recurrence rate, has brought a huge social burden to China and other countries. Understanding the pathological characteristics of cerebral thrombus can help in the selection of individualized treatment plans, thereby improving the good prognosis rate and reducing the recurrence rate of cerebral infarction patients. This article reviews the composition and imaging characteristics of cerebral thrombus, the relationship between cerebral thrombus composition and cerebral vascular recanalization therapy, the correlation between cerebral thrombus composition and the etiology of cerebral infarction, and the dynamic evolution of cerebral thrombus, to provide a more theoretical basis for the treatment of acute ischemic stroke.
References
The Compiling Team of “Report on Stroke Prevention and Control in China”, 2022, Summary of “China Stroke Prevention Report 2020”. Chinese Journal of Cerebrovascular Diseases (Electronic Edition), 19(2): 136–144.
Herpich F, Rincon F, 2020, Management of Acute Ischemic Stroke. Critical Care Medicine, 48(11): 1654–1663.
Prabhakaran S, Ruff I, Bernstein RA, 2015, Acute Stroke Intervention: A Systematic Review. JAMA, 313(14): 1451–1462.
Ullberg T, von Euler M, Wasselius J, et al., 2023, Survival and Functional Outcome following Endovascular Thrombectomy for Anterior Circulation Acute Ischemic Stroke caused By Large Vessel Occlusion in Sweden 2017–2019 — A Nationwide, Prospective, Observational Study. Interventional Neuroradiology, 29(1): 94–101.
Staessens S, Denorme F, Francois O, et al. Structural Analysis of Ischemic Stroke Thrombi: Histological Indications for Therapy Resistance. Haematologica, 105(2): 498–507.
Di Meglio L, Desilles JP, Ollivier V, et al., 2019, Acute Ischemic Stroke Thrombi have an Outer Shell that Impairs Fibrinolysis. Neurology, 93(18): 1686–1698.
Sporns PB, Hanning U, Schwindt W, et al., 2017, Ischemic Stroke: What Does the Histological Composition Tell Us About the Origin of the Thrombus? Stroke, 48(8): 2206–2210.
Khismatullin RR, Nagaswami C, Shakirova AZ, et al., 2020, Quantitative Morphology of Cerebral Thrombi Related to Intravital Contraction and Clinical Features of Ischemic Stroke, 51(12): 3640–3650.
Boeckh-Behrens T, Schubert M, Forschler A, et al., 2016, The Impact of Histological Clot Composition in Embolic Stroke. Clinical Neuroradiology, 26(2): 189–197.
Fitzgerald ST, Wang S, Dai D, et al., 2019, Platelet-rich Clots as Identified by Martius Scarlet Blue Staining are Isodense on NCCT. Journal of Neurointerventional Surgery, 11(11): 1145–1149
Marder VJ, Chute DJ, Starkman S, et al., 2006, Analysis of Thrombi Retrieved from Cerebral Arteries of Patients with Acute Ischemic Stroke. Stroke, 37(8): 2086–2093.
Han T, Tang H, Lin C, et al., 2022, Extracellular Traps and the Role in Thrombosis. Frontiers in Cardiovascular Medicine, 2022(9): 951670.
Kim SW, Lee JK, 2020, Role of HMGB1 in the Interplay between NETosis and Thrombosis in Ischemic Stroke: A Review. Cells, 9(8): 1794
Locke M, Longstaff C, 2021, Extracellular Histones Inhibit Fibrinolysis through Noncovalent and Covalent Interactions with Fibrin. Thrombosis and Haemostasis, 121(4): 464–476.
Ducroux C, Di Meglio L, Loyau S, et al., 2018, Thrombus Neutrophil Extracellular Traps Content Impair tPA-Induced Thrombolysis in Acute Ischemic Stroke. Stroke, 49(3): 754–757.
Laridan E, Denorme F, Desender L, et al., 2017, Neutrophil Extracellular Traps in Ischemic Stroke Thrombi. Annals of Neurology, 82(2): 223–232.
De Meyer SF, Deckmyn H, Vanhoorelbeke K, 2009, von Willebrand Factor to the Rescue. Blood, 113(21): 5049–5057.
Reininger AJ, 2008, VWF Attributes—Impact on Thrombus Formation. Thrombosis Research, 122(4): 9–13.
Douglas A, Fitzgerald S, Mereuta OM, et al., 2020, Platelet-rich Emboli are Associated with von Willebrand Factor Levels and Have Poorer Revascularization Outcomes. Journal of Neurointerventional Surgery, 12(6): 557–562.
Denorme F, Langhauser F, Desender L, et al., 2016, ADAMTS13-mediated Thrombolysis of t-PA-resistant Occlusions in Ischemic Stroke in Mice. Blood, 127(19): 2337–2345.
Funatsu N, Hayakawa M, Hashimoto T, et al., 2019, Vascular Wall Components in Thrombi Obtained by Acute Stroke Thrombectomy: Clinical Significance and Related Factors. Journal of Neurointerventional Surgery, 11(3): 232–236.
Bardon M, Hanson J, O’Brien B, et al., 2018, Calcified Cerebral Emboli: Incidence and Implications. Journal of Medical Imaging and Radiation Oncology, preprint.
Grau AJ, Urbanek C, Palm F, 2010, Common Infections and the Risk of Stroke. Nature Reviews Neurology, 6(12): 681–694.
Hernandez-Fernandez F, Rojas-Bartolome L, Garcia-Garcia J, et al., 2017, Histopathological and Bacteriological Analysis of Thrombus Material Extracted during Mechanical Thrombectomy in Acute Stroke Patients. Cardiovascular and Interventional Radiology, 40(12): 1851–1860.
Das S, Goldstein ED, de Havenon A, et al., 2023, Composition, Treatment, and Outcomes by Radiologically Defined Thrombus Characteristics in Acute Ischemic Stroke. Stroke, 54(6): 1685–1694.
Maurer CJ, Dobrocky T, Joachimski F, et al., 2020, Endovascular Thrombectomy of Calcified Emboli in Acute Ischemic Stroke: A Multicenter Study. American Journal of Neuroradiology, 41(3): 464–468.
Pir GJ, Parray A, Ayadathil R, et al., 2022, Platelet-Neutrophil Association in NETs-Rich Areas in the Retrieved AIS Patient Thrombi. International Journal of Molecular Sciences, 23(22): 14477.
Horie N, Shobayashi K, Morofuji Y, et al., 2019, Impact of Mechanical Thrombectomy Device on Thrombus Histology in Acute Embolic Stroke. World Neurosurgery, 2019(132): 418–422.
Santorelli A, Fitzgerald S, Douglas A, et al., 2020, Dielectric Profile of Blood Clots to Inform Ischemic Stroke Treatments. Annual International Conference of the IEEE Engineering in Medicine and Biology Society 2020, 3723–3726.
Lv J, Zhang L, Du W, et al., 2022, Functional Gold Nanoparticles for Diagnosis, Treatment and Prevention of Thrombus. Journal of Controlled Release, 2022(345): 572–585.
Alonso-Alonso ML, Perez-Mato M, Sampedro-Viana A, et al., 2022, Fibrin-Targeted Nanoparticles for Finding, Visualizing and Characterizing Blood Clots in Acute Ischemic Stroke. Pharmaceutics, 14(10): 2156.
Xiong X, Wang J, Ke J, et al., 2023, Radiomics-based Intracranial Thrombus Features on Preoperative Noncontrast CT Predicts Successful Recanalization of Mechanical Thrombectomy in Acute Ischemic Stroke. Quantitative Imaging in Medicine and Surgery, 13(2): 682–694.
Shin JW, Jeong HS, Kwon HJ, et al., 2018, High Red Blood Cell Composition in Clots is Associated with Successful Recanalization during Intra-arterial Thrombectomy. PLoS One, 13(5): e0197492.
Fitzgerald S, Wang S, Dai D, et al., 2019, Orbit Image Analysis Machine Learning Software can be used for the Histological Quantification of Acute Ischemic Stroke Blood Clots. PLoS One, 14(12): e0225841.
Hund H, Boodt N, Arrarte Terreros N, et al., 2022, Quantitative Thrombus Characteristics on Thin-slice Computed Tomography Improve Prediction of Thrombus Histopathology: Results of the MR CLEAN Registry. European Radiology, 32(11): 7811–7823.
Niesten JM, van der Schaaf IC, van der Graaf Y, et al., 2014, Predictive Value of Thrombus Attenuation on Thin-slice Non-contrast CT for Persistent Occlusion after Intravenous Thrombolysis. Cerebrovascular Diseases, 37(2): 116–122.
Brinjikji W, Duffy S, Burrows A, et al., 2017, Correlation of Imaging and Histopathology of Thrombi in Acute Ischemic Stroke with Etiology and Outcome: A Systematic Review. Journal of Neurointerventional Surgery, 9(6): 529–534.
Maurer CJ, Dobrocky T, Joachimski F, et al., 2020, Endovascular Thrombectomy of Calcified Emboli in Acute Ischemic Stroke: A Multicenter Study. American Journal of Neuroradiology, 41(3): 464–468.
Schartz D, Akkipeddi SMK, Chittaranjan S, et al., 2023, CT Hyperdense Cerebral Artery Sign Reflects Distinct Proteomic Composition in Acute Ischemic Stroke Thrombus. Journal of Neurointerventional Surgery, 15(12): 1264–1268.
Santos EM, Marquering HA, den Blanken MD, et al., 2016, Thrombus Permeability is Associated with Improved Functional Outcome and Recanalization in Patients with Ischemic Stroke. Stroke, 47(3): 732–741.
Benson JC, Fitzgerald ST, Kadirvel R, et al., 2020, Clot Permeability and Histopathology: Is a Clot’s Perviousness on CT Imaging Correlated with its Histologic Composition? Journal of Neurointerventional Surgery, 12(1): 38–42.
Berndt M, Friedrich B, Maegerlein C, et al., 2018, Thrombus Permeability in Admission Computed Tomographic Imaging Indicates Stroke Pathogenesis Based on Thrombus Histology. Stroke, 49(11): 2674–2682.
Kim SK, Yoon W, Kim TS, et al., 2015, Histologic Analysis of Retrieved Clots in Acute Ischemic Stroke: Correlation with Stroke Etiology and Gradient-Echo MRI. American Journal of Neuroradiology, 36(9): 1756–1762.
Choi MH, Park GH, Lee JS, et al., 2018, Erythrocyte Fraction Within Retrieved Thrombi Contributes to Thrombolytic Response in Acute Ischemic Stroke. Stroke, 49(3): 652–659.
Kumagai K, Hayashi M, Ueda T, et al., 2022, Three-dimensional Vessel Wall MRI to Characterize Thrombus Prior to Endovascular Thrombectomy for Large Vessel Occlusion Stroke. Journal of Neuroimaging, 32(6): 1070–1074.
Li Y, Wang H, Zhao L, et al., 2020, A Case Report of Thrombolysis Resistance: Thrombus Ultrastructure in an Ischemic Stroke Patient. BMC Neurology, 20(1): 135.
Brownlee WJ, Anderson NE, Barber PA, 2014, Intravenous Thrombolysis is Unsafe in Stroke due to Infective Endocarditis. Internal Medicine Journal, 44(2): 195–197.
Desilles JP, Di Meglio L, Delvoye F, et al., 2022, Composition and Organization of Acute Ischemic Stroke Thrombus: A Wealth of Information for Future Thrombolytic Strategies. Frontiers in Neurology, 2022(13): 870331.
Hashimoto T, Hayakawa M, Funatsu N, et al., 2016, Histopathologic Analysis of Retrieved Thrombi Associated with Successful Reperfusion after Acute Stroke Thrombectomy. Stroke, 47(12): 3035–3037.
Maekawa K, Shibata M, Nakajima H, et al., 2018, Erythrocyte-rich Thrombus is Associated with Reduced Number of Maneuvers and Procedure Time in Patients with Acute Ischemic Stroke Undergoing Mechanical Thrombectomy. Cerebrovascular Diseases Extra, 8(1): 39–49.
Sporns PB, Hanning U, Schwindt W, et al., 2017, Ischemic Stroke: Histological Thrombus Composition and Pre-Interventional CT Attenuation are Associated with Intervention Time and Rate of Secondary Embolism. Cerebrovascular Diseases, 44(5–6): 344–350.
Duffy S, McCarthy R, Farrell M, et al., 2019, Per-Pass Analysis of Thrombus Composition in Patients with Acute Ischemic Stroke Undergoing Mechanical Thrombectomy. Stroke, 50(5): 1156–1163.
Ni XY, Wu L, Zhao WD, et al., 2021, Exploration of the Relationship between Embolic Components and Surgical Process and Clinical Outcomes in Acute Ischemic Stroke. Chinese Journal of Neurology, 54(7): 670–676.
Delvoye F, Di Meglio L, Consoli A, et al., 2022, High Thrombus Platelet Content is Associated with a Lower Rate of First Pass Effect in Stroke Treated by Endovascular Therapy. European Stroke Journal, 7(4): 376–383.
Yoo AJ, Andersson T, 2017, Thrombectomy in Acute Ischemic Stroke: Challenges to Procedural Success. Journal of Stroke, 19(2): 121–130.
Gersh KC, Nagaswami C, Weisel JW, 2009, Fibrin Network Structure and Clot Mechanical Properties are Altered by Incorporation of Erythrocytes. Thrombosis and Haemostasis, 102(6): 1169–1175.
Gunning GM, McArdle K, Mirza M, et al., 2018, Clot Friction Variation with Fibrin Content; Implications for Resistance to Thrombectomy. Journal of Neurointerventional Surgery, 10(1): 34–38.
Boodt N, Snouckaert van Schauburg PRW, Hund HM, et al., 2021, Mechanical Characterization of Thrombi Retrieved with Endovascular Thrombectomy in Patients with Acute Ischemic Stroke. Stroke, 52(8): 2510–2517.
Sporns PB, Jeibmann A, Minnerup J, et al., 2019, Histological Clot Composition is Associated with Preinterventional Clot Migration in Acute Stroke Patients. Stroke, 50(8): 2065–2071.
Mohammaden MH, Haussen DC, Perry da Camara C, et al., 2021, Hyperdense Vessel Sign as a Potential Guide for the Choice of Stent Retriever Versus Contact Aspiration as First-line Thrombectomy Strategy. Journal of Neurointerventional Surgery, 13(7): 599–604.
Bourcier R, Mazighi M, Labreuche J, et al., 2018, ASTER Trial Investigators. Susceptibility Vessel Sign in the ASTER Trial: Higher Recanalization Rate and More Favourable Clinical Outcome after First Line Stent Retriever Compared to Contact Aspiration. Journal of Stroke, 20(2): 268–276.
Kaesmacher J, Boeckh-Behrens T, Simon S, et al., 2017, Risk of Thrombus Fragmentation during Endovascular Stroke Treatment. American Journal of Neuroradiology, 38(5): 991–998.
Rossi R, Douglas A, Gil SM, et al., 2023, S100b in Acute Ischemic Stroke Clots is a Biomarker for Post-thrombectomy Intracranial Hemorrhages. Frontiers in Neurology, 2023(13): 1067215.
Marder VJ, Chute DJ, Starkman S, et al., 2006, Analysis of Thrombi Retrieved from Cerebral Arteries of Patients with Acute Ischemic Stroke. Stroke, 37(8): 2086–2093.
Ogata J, Yutani C, Otsubo R, et al., 2008, Heart and Vessel Pathology Underlying Brain Infarction in 142 Stroke Patients. Annals of Neurology, 63(6): 770–781.
Ahn SH, Hong R, Choo IS, et al., 2016, Histologic Features of Acute Thrombi Retrieved from Stroke Patients during Mechanical Reperfusion Therapy. International Journal of Stroke, 11(9): 1036–1044.
Niesten JM, van der Schaaf IC, van Dam L, et al., 2014, Histopathologic Composition of Cerebral Thrombi of Acute Stroke Patients is Correlated with Stroke Subtype and Thrombus Attenuation. PLoS One, 9(2): e88882.
Boeckh-Behrens T, Kleine JF, Zimmer C, et al., 2016, Thrombus Histology Suggests Cardioembolic Cause in Cryptogenic Stroke. Stroke, 47(7): 1864–1871.
Hund HM, Boodt N, Hansen D, et al., 2023, Association between Thrombus Composition and Stroke Etiology in the MR CLEAN Registry Biobank. Neuroradiology, 65(5): 933–943.
Fitzgerald S, Dai D, Wang S, et al., 2019, Platelet-Rich Emboli in Cerebral Large Vessel Occlusion are Associated with a Large Artery Atherosclerosis Source. Stroke, 50(7): 1907–1910.
Gong L, Zheng X, Feng L, et al., 2019, Bridging Therapy Versus Direct Mechanical Thrombectomy in Patients with Acute Ischemic Stroke due to Middle Cerebral Artery Occlusion: A Clinical-Histological Analysis of Retrieved Thrombi. Cell Transplant, 28(6): 684–690.
Simons N, Mitchell P, Dowling R, et al., 2015, Thrombus Composition in Acute Ischemic Stroke: A Histopathological Study of Thrombus Extracted by Endovascular Retrieval. Journal of Neuroradiology, 42(2): 86–92.
Huang J, Killingsworth MC, Bhaskar SMM, 2022, Is Composition of Brain Clot Retrieved by Mechanical Thrombectomy Associated with Stroke Aetiology and Clinical Outcomes in Acute Ischemic Stroke? A Systematic Review and Meta-Analysis. Neurology International, 14(4): 748–770.
Larco JA, Abbasi M, Madhani SI, et al., 2022, Correlation of Neutrophil to Lymphocyte Ratio with Expression of Neutrophil Extracellular Traps within Stroke Emboli. Interventional Neuroradiology, 28(6): 726–730.
Chen R, Zeng X, Liu Y, et al., 2022, No Histological Difference between Large Atherosclerotic and Cardiogenic Embolic Thrombus. Oxidative Medicine and Cellular Longevity, 4845264.
Gunning GM, McArdle K, Mirza M, et al., 2018, Clot Friction Variation with Fibrin Content; Implications for Resistance to Thrombectomy. Journal of Neurointerventional Surgery, 10(1): 34–38.
Kauw F, Velthuis BK, Takx RAP, et al., 2023, Detection of Cardioembolic Sources with Nongated Cardiac Computed Tomography Angiography in Acute Stroke: Results from the ENCLOSE Study. Stroke, 54(3): 821–830.
Liao Y, Guan M, Liang D, et al., 2020, Differences in Pathological Composition Among Large Artery Occlusion Cerebral Thrombi, Valvular Heart Disease Atrial Thrombi and Carotid Endarterectomy Plaques. Frontiers in Neurology, 2020(11): 811.
Dargazanli C, Rigau V, Eker O, et al., 2016, High CD3+ Cells in Intracranial Thrombi Represent a Biomarker of Atherothrombotic Stroke. PLoS One, 11(5): e0154945.
Baek BH, Kim HS, Yoon W, et al., 2018, Inflammatory Mediator Expression within Retrieved Clots in Acute Ischemic Stroke. Annals of Clinical and Translational Neurology, 5(3): 273–279.
Meretoja A, Keshtkaran M, Saver JL, et al., 2014, Stroke Thrombolysis: Save a Minute, Save a Day. Stroke, 45(4): 1053–1058.
Hill MD, Demchuk AM, Goyal M, et al., 2014, Alberta Stroke Program Early Computed Tomography Score to Select Patients for Endovascular Treatment: Interventional Management of Stroke (IMS)-III Trial. Stroke, 45(2): 444–449.
Wolberg AS, 2007, Thrombin Generation and Fibrin Clot Structure. Blood Reviews, 21(3): 131–142.
Van der Spuy WJ, Pretorius E, 2013, Interaction of Red Blood Cells Adjacent to and within a Thrombus in Experimental Cerebral Ischaemia. Thrombosis Research, 132(6): 718–723.
Wohner N, Sotonyi P, Machovich R, et al., 2011, Lytic Resistance of Fibrin Containing Red Blood Cells. Arteriosclerosis, Thrombosis, and Vascular Biology, 31(10): 2306–2313.
Joundi RA, Menon BK, 2021, Thrombus Composition, Imaging, and Outcome Prediction in Acute Ischemic Stroke. Neurology, 97(20): 68–78.
Laridan E, Denorme F, Desender L, et al., 2017, Neutrophil Extracellular Traps in Ischemic Stroke Thrombi. Annals of Neurology, 82(2): 223–232.
Hacke W, Donnan G, Fieschi C, et al., 2004, Association of Outcome with Early Stroke Treatment: Pooled Analysis of ATLANTIS, ECASS, and NINDS rt-PA Stroke Trials. Lancet, 363(9411): 768–774.
Saver JL, Goyal M, van der Lugt A, et al., 2016, HERMES Collaborators. Time to Treatment with Endovascular Thrombectomy and Outcomes from Ischemic Stroke: A Meta-analysis. JAMA, 316(12): 1279–1288.
Bourcier R, Goyal M, Liebeskind DS, et al., 2019, Association of Time from Stroke Onset to Groin Puncture with Quality of Reperfusion after Mechanical Thrombectomy: A Meta-analysis of Individual Patient Data From 7 Randomized Clinical Trials. JAMA Neurology, 76(4): 405–411.
Kim YD, Nam HS, Kim SH, et al., 2015, Time-Dependent Thrombus Resolution after Tissue-Type Plasminogen Activator in Patients with Stroke and Mice. Stroke, 46(7): 1877–1882.
Pikija S, Magdic J, Trkulja V, et al., 2016, Intracranial Thrombus Morphology and Composition Undergoes Time-Dependent Changes in Acute Ischemic Stroke: A CT Densitometry Study. International Journal of Molecular Sciences, 17(11): 1959.
Krajickova D, Krajina A, Steiner I, et al., 2018, Fibrin Clot Architecture in Acute Ischemic Stroke Treated with Mechanical Thrombectomy with Stent-Retrievers – Cohort Study. Circulation Journal, 82(3): 866–873.
Abbasi M, Arturo Larco J, Mereuta MO, et al., 2022, Diverse Thrombus Composition in Thrombectomy Stroke Patients with Longer Time to Recanalization. Thrombosis Research, 2022(209): 99–104.
Kitano T, Hori Y, Okazaki S, et al., 2022, An Older Thrombus Delays Reperfusion after Mechanical Thrombectomy for Ischemic Stroke. Thrombosis and Haemostasis, 122(3): 415–426.
Lin J, Guan M, Liao Y, et al., 2023, An Old Thrombus May Potentially Identify Patients at Higher Risk of Poor Outcome in Anterior Circulation Stroke Undergoing Thrombectomy. Neuroradiology, 65(2): 381–390.