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

RESEARCH ARTICLE High red blood cell composition in clots is associated with successful recanalization during intra-arterial thrombectomy Jong Wook Shin1,2, Hye Seon Jeong1,2, Hyon-Jo Kwon1,3, Kyu Sang Song4, Jei Kim1,2* 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 a1111111111 a1111111111 a1111111111 a1111111111 a1111111111 OPEN ACCESS Citation: Shin JW, Jeong HS, Kwon H-J, Song KS, Kim J (2018) High red blood cell composition in clots is associated with successful recanalization during intra-arterial thrombectomy. PLoS ONE 13 (5): e0197492. https://doi.org/10.1371/journal. pone.0197492 Editor: Hugo ten Cate, Maastricht University Medical Center, NETHERLANDS Received: December 12, 2017 Accepted: May 3, 2018 Published: May 21, 2018 Copyright: © 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. * 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. Data Availability Statement: All relevant data are within the paper and its Supporting Information files. Funding: The present study was supported by a Research Fund of Chungnam National University 2016 (for Jei Kim, MD). Introduction Competing interests: The authors have declared that no competing interests exist. Ischemic stroke is a serious condition with a high risk of lasting neurological disability. Recanalization after the occlusion of an intracranial artery is important to restoring cerebral PLOS ONE | https://doi.org/10.1371/journal.pone.0197492 May 21, 2018 1 / 13 Red blood cell-dominant clot and recanalization perfusion below the occluded site. [1] In particular, successful recanalization within the time window is critical for improving the clinical outcome of acute ischemic stroke patients. [2] Intra-arterial thrombectomy (IAT) is effective in ensuring reperfusion following occlusion of intracranial vessels in patients with acute ischemic stroke [3]. Rapid reperfusion of the occluded vessel and surrounding regions within 6 h of stroke onset has been regarded as critical for achieving good functional outcomes following IAT [1,2,4,5]. However, reperfusion within this time window is unsuccessful in approximately two-fifths of patients treated via IAT [4]. Increases in the interval between symptom onset and recanalization (e.g., late arrival at the emergency room (ER) following symptom onset and delay of IAT following admission) significantly increase the risk of unsuccessful reperfusion [6]. Additional studies have revealed that individual variations in vessel anatomy [7] and intracranial collateral development [8] may also contribute to delayed or unsuccessful recanalization. Recently, several research groups have evaluated the association between the histological composition of clots retrieved after IAT and successful reperfusion among patients with various subtypes of stroke [9–13]. Such studies have examined the effect of red blood cell (RBC), fibrin/platelet, and white blood cell (WBC) composition within retrieved clots on rates of successful reperfusion using specific retrieval devices, as well as the influence of clot signs such as hyperdense vessels on initial computed tomography (CT) and blooming artifacts on gradientecho magnetic resonance imaging (GRE MRI) [9–13]. However, in these previous studies, recanalization status was evaluated based on the final reperfusion status of the occluded vessels following the complete IAT intervention, rather than after each catheterization step performed during IAT [10–13]. IAT interventions typically require several catheterization steps to ensure complete reperfusion, as unsuccessful reperfusion occurs in some trials even after clot retrieval. Thus, the final reperfusion status obtained after multiple catheterizations is inappropriate for analyzing the association between clot composition and clot retrieval/successful recanalization, which should be evaluated after the individual catheterization steps during IAT. The present study aimed to evaluate the association between the histological composition of retrieved clots and successful recanalization after separate retrieval trials during IAT. We also compared the composition of individual clots according to stroke subtypes, clot retrieval devices, and the presence of clot signs on initial brain images. Materials and methods Patients A total of 46 patients who had undergone IAT for the treatment of acute ischemic stroke between February 2014 and May 2017 were enrolled in the present study. All patients met the following inclusion criteria: age >18 years, time from onset to groin puncture <6 h, National Institutes of Health Stroke Scale (NIHSS) score 4, occlusion (...truncated)