Histological analysis of thrombi retrieved after acute ischemic stroke from large vessel occlusion: from research to clinical practice

Ettore Nicolini , Manuela De Michele , Anne Falcou , Luca Petraglia , Irene Berto , Danilo Toni

Vessel Plus ›› 2022, Vol. 6 ›› Issue (1) : 2

PDF
Vessel Plus ›› 2022, Vol. 6 ›› Issue (1) :2 DOI: 10.20517/2574-1209.2021.78
Review

Histological analysis of thrombi retrieved after acute ischemic stroke from large vessel occlusion: from research to clinical practice

Author information +
History +
PDF

Abstract

Emergent reperfusion therapies have improved acute ischemic stroke prognosis, but many patients are still bound to bad clinical outcome, probably because of our incomplete knowledge of its pathophysiology. Thanks to mechanical thrombectomy, occluding material is available for histological analysis. Several studies investigated the possible relationship between thrombus composition and clinical, procedural, and radiological variables of acute ischemic stroke. The potential value of thrombus analysis as a tool for clinical practice and research is still not defined, as data from the literature are heterogeneous and sometimes conflicting. We propose a review of the existing literature regarding histological analysis of thrombi in acute ischemic stroke. We classified articles on clot composition according to the clinical variable explored in each study. We first distinguished articles about etiology, procedural, and radiological variables, and then we performed a subclassification for each group. This review could help both in the interpretation of thrombus analysis in clinical practice and in its usage for future research.

Keywords

Stroke / thrombus / mechanical thrombectomy / histology

Cite this article

Download citation ▾
Ettore Nicolini, Manuela De Michele, Anne Falcou, Luca Petraglia, Irene Berto, Danilo Toni. Histological analysis of thrombi retrieved after acute ischemic stroke from large vessel occlusion: from research to clinical practice. Vessel Plus, 2022, 6(1): 2 DOI:10.20517/2574-1209.2021.78

登录浏览全文

4963

注册一个新账户 忘记密码

References

[1]

Rohan V,Tupy R.Length of occlusion predicts recanalization and outcome after intravenous thrombolysis in middle cerebral artery stroke.Stroke2014;45:2010-7

[2]

Johnson CO,Roth GA.Global, regional, and national burden of stroke, 1990-2016: a systematic analysis for the Global Burden of Disease Study 2016.Lancet Neurol2019;18:439-58 PMCID:PMC6494974

[3]

Goyal M,van Zwam WH.Endovascular thrombectomy after large-vessel ischaemic stroke: a meta-analysis of individual patient data from five randomised trials.Lancet2016;387:1723-31

[4]

Meyer SF, Andersson T, Baxter B, et al; Clot Summit Group. Analyses of thrombi in acute ischemic stroke: a consensus statement on current knowledge and future directions.Int J Stroke2017;12:606-14

[5]

Kuriakose D.Pathophysiology and treatment of stroke: present status and future perspectives.Int J Mol Sci2020;21:7609 PMCID:PMC7589849

[6]

Staessens S,Andersson T.Histological stroke clot analysis after thrombectomy: technical aspects and recommendations.Int J Stroke2020;15:467-76

[7]

Nouh A,Hussain M,Ollenschleger M.Clot composition of embolic strokes of undetermined source: a feasibility study.BMC Neurol2020;20:383 PMCID:PMC7580014

[8]

Sporns PB,Schwindt W.Ischemic stroke: histological thrombus composition and pre-interventional CT attenuation are associated with intervention time and rate of secondary embolism.Cerebrovasc Dis2017;44:344-50

[9]

Boeckh-Behrens T,Zimmer C.Thrombus histology suggests cardioembolic cause in cryptogenic stroke.Stroke2016;47:1864-71

[10]

Liao Y,Liang D.Differences in pathological composition among large artery occlusion cerebral thrombi, valvular heart disease atrial thrombi and carotid endarterectomy plaques.Front Neurol2020;11:811 PMCID:PMC7427050

[11]

Niesten JM,van Dam L.Histopathologic composition of cerebral thrombi of acute stroke patients is correlated with stroke subtype and thrombus attenuation.PLoS One2014;9:e88882 PMCID:PMC3921255

[12]

Goebel J,Wanke I.Is histologic thrombus composition in acute stroke linked to stroke etiology or to interventional parameters?.AJNR Am J Neuroradiol2020;41:650-7 PMCID:PMC7144659

[13]

Duffy S,Farrell M.Per-pass analysis of thrombus composition in patients with acute ischemic stroke undergoing mechanical thrombectomy.Stroke2019;50:1156-63

[14]

Khismatullin RR,Shakirova AZ.Quantitative morphology of cerebral thrombi related to intravital contraction and clinical features of ischemic stroke.Stroke2020;51:3640-50

[15]

Kim B,Jin SC.Development of a predictive scale for cardioembolic stroke using extracted thrombi and angiographic findings.J Clin Neurosci2020;73:224-30

[16]

Fitzgerald S,Wang S.Platelet-rich emboli in cerebral large vessel occlusion are associated with a large artery atherosclerosis source.Stroke2019;50:1907-10 PMCID:PMC6910081

[17]

Kim SK,Kim TS,Heo TW.Histologic analysis of retrieved clots in acute ischemic stroke: correlation with stroke etiology and gradient-echo MRI.AJNR Am J Neuroradiol2015;36:1756-62 PMCID:PMC7968760

[18]

Caplan LR.Antiplatelet therapy in stroke prevention: present and future.Cerebrovasc Dis2006;21 Suppl 1:1-6

[19]

Itsekson Hayosh Z,Shelestovich N.In-thrombus thrombin secretion: a new diagnostic marker of atrial fibrillation in cryptogenic stroke.J Neurointerv Surg2020;neurintsurg-2020

[20]

Meyer SF, Denorme F, Langhauser F, Geuss E, Fluri F, Kleinschnitz C. Thromboinflammation in stroke brain damage.Stroke2016;47:1165-72

[21]

Schuhmann MK,Kleinschnitz C.Immunohistochemical analysis of cerebral thrombi retrieved by mechanical thrombectomy from patients with acute ischemic stroke.Int J Mol Sci2016;17:298 PMCID:PMC4813162

[22]

Sporns PB,Schwindt W.Ischemic stroke: what does the histological composition tell us about the origin of the thrombus?.Stroke2017;48:2206-10

[23]

Boeckh-Behrens T,Förschler A.The impact of histological clot composition in embolic stroke.Clin Neuroradiol2016;26:189-97

[24]

Dargazanli C,Eker O.High CD3+ cells in intracranial thrombi represent a biomarker of atherothrombotic stroke.PLoS One2016;11:e0154945 PMCID:PMC4859469

[25]

Novotny J,Titova A.Thrombus NET content is associated with clinical outcome in stroke and myocardial infarction.Neurology2020;94:e2346-60

[26]

Brinkmann V,Goosmann C.Neutrophil extracellular traps kill bacteria.Science2004;303:1532-5

[27]

Laridan E,Desender L.Neutrophil extracellular traps in ischemic stroke thrombi.Ann Neurol2017;82:223-32

[28]

Savchenko AS,Seidman MA.Neutrophil extracellular traps form predominantly during the organizing stage of human venous thromboembolism development.J Thromb Haemost2014;12:860-70 PMCID:PMC4055516

[29]

Meglio L, Desilles JP, Solonomenjanahary M, et al; compoCLOT study group†. DNA content in ischemic stroke thrombi can help identify cardioembolic strokes among strokes of undetermined cause.Stroke2020;51:2810-6

[30]

Valente M,Cordato D,Cappelen-Smith C.The diagnostic utility of routine clot analysis after endovascular thrombectomy in a patient with systemic lupus erythematosus and antiphospholipid syndrome.J Clin Neurosci2019;70:247-9

[31]

Sgreccia A,Desilles JP.COMPO-Clot InvestigatorsAssociation between acute ischemic stroke etiology and macroscopic aspect of retrieved clots: is a clot's color a warning light for underlying pathologies?.J Neurointerv Surg2019;11:1197-200

[32]

Khismatullin RR,Weisel JW.Age-dependent differential staining of fibrin in blood clots and thrombi.BioNanoSci2020;10:370-4

[33]

Sallustio F,Legge S di.Histological features of intracranial thrombo - emboli predict response to endovascular therapy for acute ischemic stroke.J Neurol Disord Stroke2015;3:1-5

[34]

Bhaskar S,Cappelen-Smith C.Clot histopathology in ischemic stroke with infective endocarditis.Can J Neurol Sci2019;46:331-6

[35]

Hernández-Fernández F,García-García J.Histopathological and bacteriological analysis of thrombus material extracted during mechanical thrombectomy in acute stroke patients.Cardiovasc Intervent Radiol2017;40:1851-60

[36]

Abdel-Wahed L,Hayakawa M.Retrieved arterial clot helps guide antibiotic therapy in infective endocarditis.Am J Med2019;132:e795-6

[37]

Khashim Z,Kadirvel R.Clots retrieved by mechanical thrombectomy from acute ischemic stroke patients show no evidence of bacteria.Interv Neuroradiol2019;25:502-7 PMCID:PMC6777113

[38]

Rosenfeld ME.Inflammation and atherosclerosis: direct versus indirect mechanisms.Curr Opin Pharmacol2013;13:154-60 PMCID:PMC3654071

[39]

Rost NS,Kase CS.Plasma concentration of C-reactive protein and risk of ischemic stroke and transient ischemic attack: the Framingham study.Stroke2001;32:2575-9

[40]

Patrakka O,Tuomisto S.Oral bacterial signatures in cerebral thrombi of patients with acute ischemic stroke treated with thrombectomy.J Am Heart Assoc2019;8:e012330 PMCID:PMC6585368

[41]

Higashida RT,Roberts H.Technology Assessment Committee of the American Society of Interventional and Therapeutic NeuroradiologyTechnology Assessment Committee of the Society of Interventional RadiologyTrial design and reporting standards for intra-arterial cerebral thrombolysis for acute ischemic stroke.Stroke2003;34:e109-37

[42]

Shin JW,Kwon HJ,Kim J.High red blood cell composition in clots is associated with successful recanalization during intra-arterial thrombectomy.PLoS One2018;13:e0197492 PMCID:PMC5962078

[43]

Hashimoto T,Funatsu N.Histopathologic analysis of retrieved thrombi associated with successful reperfusion after acute stroke thrombectomy.Stroke2016;47:3035-7

[44]

Douglas A,Mereuta OM.Platelet-rich emboli are associated with von Willebrand factor levels and have poorer revascularization outcomes.J Neurointerv Surg2020;12:557-62

[45]

Gunning GM,Mirza M,Gilvarry M.Clot friction variation with fibrin content; implications for resistance to thrombectomy.J Neurointerv Surg2018;10:34-8

[46]

Kim OV,Alber MS.Quantitative structural mechanobiology of platelet-driven blood clot contraction.Nat Commun2017;8:1274 PMCID:PMC5668372

[47]

Staessens S,Francois O.Structural analysis of ischemic stroke thrombi: histological indications for therapy resistance.Haematologica2020;105:498-507 PMCID:PMC7012484

[48]

Weafer FM,Machado I.Characterization of strut indentation during mechanical thrombectomy in acute ischemic stroke clot analogs.J Neurointerv Surg2019;11:891-7

[49]

Maekawa K,Nakajima H.Erythrocyte-rich thrombus is associated with reduced number of maneuvers and procedure time in patients with acute ischemic stroke undergoing mechanical thrombectomy.Cerebrovasc Dis Extra2018;8:39-49 PMCID:PMC5836222

[50]

Fitzgerald S,Mereuta OM.Per-pass analysis of acute ischemic stroke clots: impact of stroke etiology on extracted clot area and histological composition.J Neurointerv Surg2020;neurintsurg-2020:

[51]

Johnson S,Gounis MJ.Mechanical behavior of in vitro blood clots and the implications for acute ischemic stroke treatment.J Neurointerv Surg2020;12:853-7

[52]

Fitzgerald S,Thornton J.Preclinical evaluation of Millipede 088 intracranial aspiration catheter in cadaver and in vitro thrombectomy models.J Neurointerv Surg2021;13:447-52 PMCID:PMC8053321

[53]

Ducroux C,Loyau S.Thrombus neutrophil extracellular traps content impair tPA-induced thrombolysis in acute ischemic stroke.Stroke2018;49:754-7

[54]

Longstaff C,Sótonyi P.Mechanical stability and fibrinolytic resistance of clots containing fibrin, DNA, and histones.J Biol Chem2013;288:6946-56 PMCID:PMC3591605

[55]

Sporns PB,Minnerup J.Histological clot composition is associated with preinterventional clot migration in acute stroke patients.Stroke2019;50:2065-71

[56]

Sporns PB,Psychogios MN.Small thrombus size, thrombus composition, and poor collaterals predict pre-interventional thrombus migration.J Neurointerv Surg2021;13:409-14

[57]

Maegerlein C,Berndt M.Impact of histological thrombus composition on preinterventional thrombus migration in patients with acute occlusions of the middle cerebral artery.Interv Neuroradiol2018;24:70-5 PMCID:PMC5772536

[58]

Ye G,Chen K.Risk of secondary embolism events during mechanical thrombectomy for acute ischemic stroke: a single-center study based on histological analysis.Clin Neurol Neurosurg2020;193:105749

[59]

Kaesmacher J,Simon S.Risk of thrombus fragmentation during endovascular stroke treatment.AJNR Am J Neuroradiol2017;38:991-8 PMCID:PMC7960366

[60]

Kirchhofer D,Baumgartner HR.Specific accumulation of circulating monocytes and polymorphonuclear leukocytes on platelet thrombi in a vascular injury model.Blood1997;89:1270-8

[61]

Imamura T,Nakamura S.New functions of neutrophils in the arthus reaction: expression of tissue factor, the clotting initiator, and fibrinolysis by elastase.Lab Invest2002;82:1287-95

[62]

Komorowicz E,Léránt I.Flow rate-modulated dissolution of fibrin with clot-embedded and circulating proteases.Circ Res1998;82:1102-8

[63]

Singh P,Reinhard M,Taschner CA.Immunohistochemical analysis of thrombi retrieved during treatment of acute ischemic stroke: does stent-retriever cause intimal damage?.Stroke2013;44:1720-2

[64]

Funatsu N,Hashimoto T.Vascular wall components in thrombi obtained by acute stroke thrombectomy: clinical significance and related factors.J Neurointerv Surg2019;11:232-6

[65]

Horie N,Morofuji Y.Impact of mechanical thrombectomy device on thrombus histology in acute embolic stroke.World Neurosurg2019;132:e418-22

[66]

Choi MH,Lee JS.Erythrocyte fraction within retrieved thrombi contributes to thrombolytic response in acute ischemic stroke.Stroke2018;49:652-9

[67]

Gong L,Feng L.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 Transplant2019;28:684-90 PMCID:PMC6686432

[68]

Ahn SH,Choo IS.Histologic features of acute thrombi retrieved from stroke patients during mechanical reperfusion therapy.Int J Stroke2016;11:1036-44

[69]

Krajíčková D,Šteiner I.Fibrin clot architecture in acute ischemic stroke treated with mechanical thrombectomy with stent-retrievers - cohort study.Circ J2018;82:866-73

[70]

Rossi R,Molina S.The administration of rtPA before mechanical thrombectomy in acute ischemic stroke patients is associated with a significant reduction of the retrieved clot area but it does not influence revascularization outcome.J Thromb Thrombolysis2021;51:545-51

[71]

Kim YD,Kim SH.Time-dependent thrombus resolution after tissue-type plasminogen activator in patients with stroke and mice.Stroke2015;46:1877-82

[72]

Collet JP,Lesty C.Altered fibrin architecture is associated with hypofibrinolysis and premature coronary atherothrombosis.Arterioscler Thromb Vasc Biol2006;26:2567-73

[73]

Mehta BP.Should clot composition affect choice of endovascular therapy?.Neurology2012;79:S63-7

[74]

Di Meglio L,Ollivier V.Acute ischemic stroke thrombi have an outer shell that impairs fibrinolysis.Neurology2019;93:e1686-98 PMCID:PMC6946479

[75]

Prochazka V,Czerny D.The role of von willebrand factor, ADAMTS13, and cerebral artery thrombus composition in patient outcome following mechanical thrombectomy for acute ischemic stroke.Med Sci Monit2018;24:3929-45 PMCID:PMC6029516

[76]

Liebeskind DS,Yong WH.CT and MRI early vessel signs reflect clot composition in acute stroke.Stroke2011;42:1237-43 PMCID:PMC3094751

[77]

Fitzgerald ST,Dai D.Platelet-rich clots as identified by Martius Scarlet Blue staining are isodense on NCCT.J Neurointerv Surg2019;11:1145-9 PMCID:PMC7754082

[78]

Brinjikji W,Burrows A.Correlation of imaging and histopathology of thrombi in acute ischemic stroke with etiology and outcome: a systematic review.J Neurointerv Surg2017;9:529-34 PMCID:PMC6697418

[79]

Songsaeng D,Sakarunchai I.Efficacy of thrombus density on noninvasive computed tomography neuroimaging for predicting thrombus pathology and patient outcome after mechanical thrombectomy in acute ischemic stroke.Asian J Neurosurg2019;14:795-800 PMCID:PMC6702996

[80]

Hanning U,Psychogios MN.Imaging-based prediction of histological clot composition from admission CT imaging.J Neurointerv Surg2021;neurintsurg-2020:

[81]

Berndt M,Maegerlein C.Thrombus permeability in admission computed tomographic imaging indicates stroke pathogenesis based on thrombus histology.Stroke2018;49:2674-82

[82]

Benson JC,Kadirvel R.Clot permeability and histopathology: is a clot's perviousness on CT imaging correlated with its histologic composition?.J Neurointerv Surg2020;12:38-42 PMCID:PMC7744246

[83]

Velasco Gonzalez A,Görlich D.Clot analog attenuation in non-contrast CT predicts histology: an experimental study using machine learning.Transl Stroke Res2020;11:940-9

[84]

Borggrefe J,Mirza M.Differentiation of clot composition using conventional and dual-energy computed tomography.Clin Neuroradiol2018;28:515-22

[85]

Simons N,Dowling R,Yan B.Thrombus composition in acute ischemic stroke: a histopathological study of thrombus extracted by endovascular retrieval.J Neuroradiol2015;42:86-92

[86]

Santos EM,Treurniet KM.DUST InvestigatorsPermeable thrombi are associated with higher intravenous recombinant tissue-type plasminogen activator treatment success in patients with acute ischemic stroke.Stroke2016;47:2058-65

[87]

Santos EM,den Blanken MD.MR CLEAN InvestigatorsThrombus permeability is associated with improved functional outcome and recanalization in patients with ischemic stroke.Stroke2016;47:732-41

[88]

Berge E,Audebert H.European Stroke Organisation (ESO) guidelines on intravenous thrombolysis for acute ischaemic stroke.Eur Stroke J2021;6:I-LXII PMCID:PMC7995316

[89]

Turc G,Fischer U.European Stroke Organisation (ESO) - European Society for Minimally Invasive Neurological Therapy (ESMINT) guidelines on mechanical thrombectomy in acute ischaemic strokeendorsed by stroke alliance for Europe (SAFE).Eur Stroke J2019;4:6-12 PMCID:PMC6533858

[90]

Rovira A,Alvarez-Sabín J.Hyperacute ischemic stroke: middle cerebral artery susceptibility sign at echo-planar gradient-echo MR imaging.Radiology2004;232:466-73

[91]

Janot K,Fromont-Hankard G.Quantitative estimation of thrombus-erythrocytes using MRI. A phantom study with clot analogs and analysis by statistic regression models.J Neurointerv Surg2020;12:181-5

[92]

Blat A,Chrabaszcz K.FTIR, Raman and AFM characterization of the clinically valid biochemical parameters of the thrombi in acute ischemic stroke.Sci Rep2019;9:15475 PMCID:PMC6820737

[93]

Li C,Reif R,Wang RK.Determining elastic properties of skin by measuring surface waves from an impulse mechanical stimulus using phase-sensitive optical coherence tomography.J R Soc Interface2012;9:831-41 PMCID:PMC3306653

[94]

Liu X,Wen C.Effect of pathological heterogeneity on shear wave elasticity imaging in the staging of deep venous thrombosis.PLoS One2017;12:e0179103 PMCID:PMC5470690

[95]

Liu HC,Ding YH.Characterizing blood clots using acoustic radiation force optical coherence elastography and ultrasound shear wave elastography.Phys Med Biol2021;66:035013 PMCID:PMC7880883

[96]

Berndt M,Steiger K.Thrombus histology of basilar artery occlusions: are there differences to the anterior circulation?.Clin Neuroradiol2020;

[97]

Marder VJ,Starkman S.Analysis of thrombi retrieved from cerebral arteries of patients with acute ischemic stroke.Stroke2006;37:2086-93

[98]

Gersh KC,Muzykantov V,Weisel JW.The spatial dynamics of fibrin clot dissolution catalyzed by erythrocyte-bound vs. free fibrinolytics.J Thromb Haemost2010;8:1066-74 PMCID:PMC2890030

[99]

Ye G,Qi P.The role of diabetes mellitus on the thrombus composition in patients with acute ischemic stroke.Interv Neuroradiol2020;26:329-36 PMCID:PMC7254620

[100]

Grant PJ.Diabetes mellitus as a prothrombotic condition.J Intern Med2007;262:157-72

[101]

Arboix A,Lowak M.Gender differences and woman-specific trends in acute stroke: results from a hospital-based registry (1986-2009).Clin Neurol Neurosurg2014;127:19-24

[102]

Fraser JF,Gorman AA.The blood and clot thrombectomy registry and collaboration (BACTRAC) protocol: novel method for evaluating human stroke.J Neurointerv Surg2019;11:265-70

PDF

77

Accesses

0

Citation

Detail

Sections
Recommended

/