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      High red blood cell composition in clots is associated with successful recanalization during intra-arterial thrombectomy

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          Abstract

          We evaluated the composition of individual clots retrieved during intra-arterial thrombectomy in relation to recanalization success, stroke subtype, and the presence of clot signs on initial brain images. We analyzed clot and interventional data from 145 retrieval trials performed for 37 patients (69.5±14.0 years, 20 men, large artery atherosclerosis, n = 7; cardioembolism, n = 22; undetermined etiology, n = 8) who had undergone intra-arterial thrombectomy. Rates of clot retrieval and successful recanalization (Arterial Occlusive Lesion score of 2–3) for separate retrieval trials were evaluated. The area occupied by red blood cell (RBC), fibrin/platelets, and white blood cell (WBC) was measured from digitized images of hematoxylin-eosin stained clots. Compositional differences were compared according to recanalization success, stroke subtype, and the presence of hyperdense clot sign on initial computed tomography and/or blooming artifact on magnetic resonance image. Of the 145 total retrieval trials (3.4±2.4 times per patient), clot was retrieved in 93 trials (64%), while recanalization was successful in 73 (50%). Fibrin/platelets (63%) occupied the greatest area in retrieved clots, followed by RBCs (33%) and WBCs (4%). Clots retrieved from successful recanalization exhibited higher RBC composition (37%) than those retrieved from non-recanalization trials (20%, p = 0.001). RBC composition was higher in cardioembolic stroke (38%) rather than large artery atherosclerosis (23%) and undetermined etiology (26%, p = 0.01). Clots exhibiting clot signs (40%) had higher RBC composition than those without clot signs (19%, p = 0.001). RBC-rich clots were associated with successful recanalization of intra-arterial thrombectomy, cardioembolic stroke, and the presence of clot-signs on initial brain images.

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          Good clinical outcome after ischemic stroke with successful revascularization is time-dependent.

          Trials of IV recombinant tissue plasminogen activator (rt-PA) have demonstrated that longer times from ischemic stroke symptom onset to initiation of treatment are associated with progressively lower likelihoods of clinical benefit, and likely no benefit beyond 4.5 hours. How the timing of IV rt-PA initiation relates to timing of restoration of blood flow has been unclear. An understanding of the relationship between timing of angiographic reperfusion and clinical outcome is needed to establish time parameters for intraarterial (IA) therapies. The Interventional Management of Stroke pilot trials tested combined IV/IA therapy for moderate-to-severe ischemic strokes within 3 hours from symptom onset. To isolate the effect of time to angiographic reperfusion on clinical outcome, we analyzed only middle cerebral artery and distal internal carotid artery occlusions with successful reperfusion (Thrombolysis in Cerebral Infarction 2-3) during the interventional procedure (<7 hours). Time to angiographic reperfusion was defined as time from stroke onset to procedure termination. Good clinical outcome was defined as modified Rankin Score 0-2 at 3 months. Among the 54 cases, only time to angiographic reperfusion and age independently predicted good clinical outcome after angiographic reperfusion. The probability of good clinical outcome decreased as time to angiographic reperfusion increased (unadjusted p = 0.02, adjusted p = 0.01) and approached that of cases without angiographic reperfusion within 7 hours. We provide evidence that good clinical outcome following angiographically successful reperfusion is significantly time-dependent. At later times, angiographic reperfusion may be associated with a poor risk-benefit ratio in unselected patients.
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            Histopathologic Composition of Cerebral Thrombi of Acute Stroke Patients Is Correlated with Stroke Subtype and Thrombus Attenuation

            Introduction We related composition of cerebral thrombi to stroke subtype and attenuation on non-contrast CT (NCCT) to gain more insight in etiopathogenesis and to validate thrombus attenuation as a new imaging biomarker for acute stroke. Methods We histopathologically investigated 22 thrombi retrieved after mechanical thrombectomy in acute stroke patients. First, thrombi were classified as fresh, lytic or organized. Second, percentages of red blood cells (RBCs), platelets and fibrin and number of red, white (respectively RBCs or platelets outnumbering other components with ≥15%) or mixed thrombi were compared between large artery atherosclerosis (LAA), cardioembolism, dissection and unknown subtype. Third, correlation between attenuation and RBCs, platelets and fibrin was calculated using Pearson's correlation coefficients (r). Results Thrombi were fresh in 73% (n = 16), lytic in 18% (n = 4) and organized in 9% (n = 2). The stroke cause was LAA in eight (36%), cardioembolism in six (27%), dissection in three (14%), and unknown in five (23%) patients. LAA thrombi showed the highest percentage RBCs (median 50 (range 35–90)), followed by dissection (35 (20–40), p = 0.05), cardioembolism (35 (5–45), p = 0.013) and unknown subtype (25 (2–40), p = 0.006). No differences in platelets (p = 0.16) and fibrin (p = 0.52) between subtypes were found. LAA thrombi were classified as red or mixed (both n = 4), cardioembolisms as mixed (n = 5) or white (n = 1) and dissection as mixed (n = 3). There was a moderate positive correlation between attenuation and RBCs (r = 0.401, p = 0.049), and weak negative correlations with platelets (r = −0.368, p = 0.09) and fibrin (r = −0.073, p = 0.75). Conclusions The majority of cerebral thrombi is fresh. There are no differences in age of thrombi between subtypes. LAA thrombi have highest percentages RBCs, cardioembolism and unknown subtype lowest. No relationship exists between subtype and platelets or fibrin percentages. We found a correlation between the RBC-component and thrombus attenuation, which improves validation of thrombus attenuation on NCCT as an imaging biomarker for stroke management.
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              Thrombectomy in Acute Ischemic Stroke: Challenges to Procedural Success

              The overwhelming clinical benefit of intra-arterial stroke therapy owes to the major advance in revascularization brought on by the current generation of thrombectomy devices. Nevertheless, there remains a sizeable proportion of patients for whom substantial reperfusion cannot be achieved or is achieved too late. This article addresses the persistent challenges that face neurointerventionists and reviews technical refinements that may help to mitigate these obstacles to procedural success. Insights from in vitro modeling and clinical research are organized around a conceptual framework that examines the interaction between the device, the thrombus and the vessel wall.
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                Author and article information

                Contributors
                Role: Formal analysisRole: MethodologyRole: SoftwareRole: Writing – original draft
                Role: Formal analysisRole: InvestigationRole: Resources
                Role: InvestigationRole: Project administrationRole: Resources
                Role: MethodologyRole: SoftwareRole: ValidationRole: Visualization
                Role: ConceptualizationRole: Data curationRole: MethodologyRole: Project administrationRole: SupervisionRole: Writing – review & editing
                Role: Editor
                Journal
                PLoS One
                PLoS ONE
                plos
                plosone
                PLoS ONE
                Public Library of Science (San Francisco, CA USA )
                1932-6203
                21 May 2018
                2018
                : 13
                : 5
                : e0197492
                Affiliations
                [1 ] Daejeon-Chungnam Regional Cerebrovascular Center, Chungnam National University Hospital, Daejeon, South Korea
                [2 ] Department of Neurology, Hospital and School of Medicine, Chungnam National University, Daejeon, South Korea
                [3 ] Department of Neurosurgery, Hospital and School of Medicine, Chungnam National University, Daejeon, South Korea
                [4 ] Department of Pathology, Hospital and School of Medicine, Chungnam National University, Daejeon, South Korea
                Maastricht University Medical Center, NETHERLANDS
                Author notes

                Competing Interests: The authors have declared that no competing interests exist.

                Author information
                http://orcid.org/0000-0002-0718-9251
                Article
                PONE-D-17-43410
                10.1371/journal.pone.0197492
                5962078
                29782513
                2b69f056-25b4-423a-a8e9-23cdba3a3291
                © 2018 Shin et al

                This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

                History
                : 12 December 2017
                : 3 May 2018
                Page count
                Figures: 3, Tables: 3, Pages: 13
                Funding
                Funded by: funder-id http://dx.doi.org/10.13039/501100002462, Chungnam National University;
                Award Recipient :
                The present study was supported by a Research Fund of Chungnam National University 2016 (for Jei Kim, MD).
                Categories
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                Medicine and Health Sciences
                Critical Care and Emergency Medicine
                Reperfusion
                Medicine and Health Sciences
                Neurology
                Cerebrovascular Diseases
                Stroke
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                Vascular Medicine
                Stroke
                Research and Analysis Methods
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