Kallmes, David F.

Background Characterization of acute ischemic stroke (AIS) clots has typically focused on two-dimensional histological analysis of the thrombus. The three-dimensional (3D) architecture and distribution of components within emboli have not been fully investigated. The aim of this study was to examine the composition and microstructure of AIS clots using histology and serial block-face scanning electron microscopy (SBFSEM). Methods As part of the multi-institutional STRIP registry, 10 consecutive AIS emboli were collected from 10 patients treated by mechanical thrombectomy. Histological and immunohistochemical analysis was performed to determine clot composition. SBFSEM was used to assess the ultrastructural organization of the clots and specific features of individual components. Results Quantification of Martius Scarlett Blue stain identified fibrin (44.4%) and red blood cells (RBCs, 32.6%) as the main components. Immunohistochemistry showed a mean platelet and von Willebrand factor content of 23.9% and 11.8%, respectively. The 3D organization of emboli varied greatly depending on the region analyzed. RBC-rich areas were composed mainly of tightly packed RBCs deformed into polyhedrocytes with scant fibrin fibers interwoven between cells. The regions with mixed composition showed thick fibrin fibers along with platelets, white blood cells and RBC clusters. Fibrin-rich areas contained dense fibrin masses with sparse RBC. In three cases, the fibrin formed a grid-like or a sponge-like pattern, likely due to thrombolytic treatment. Segmentation showed that fibrin fibers were thinner and less densely packed in these cases. Conclusions 3D-SEM provides novel and potentially clinically relevant information on clot components and ultrastructure which may help to inform thrombolytic treatment and medical device design.

AbstractEmbolectomy is one of the emergency procedures performed to remove emboli. Assessing the composition of human blood clots is an important diagnostic factor and could provide guidance for an appropriate treatment strategy for interventional physicians. Immunostaining has been used to identity compositions of clots as a gold‐standard procedure, but it is time‐consuming and cannot be performed in situ. Here, we proposed that the optical attenuation coefficient of optical coherence tomography (OCT) can be a reliable indicator as a new imaging modality to differentiate clot compositions. Fifteen human blood clots with multiple red blood cell (RBC) compositions from 21% to 95% were prepared using healthy human whole blood. A homogeneous gelatin phantom experiment and numerical simulation based on the Lambert–Beer's law were examined to verify the validity of the attenuation coefficient estimation. The results displayed that optical attenuation coefficients were strongly correlated with RBC compositions. We reported that attenuation coefficients could be a promising biomarker to guide the choice of an appropriate interventional device in a clinical setting and assist in characterizing blood clots.

Background Initial studies investigating correlations between stroke etiology and clot composition are conflicting and do not account for clot size as determined by area. Radiological studies have shown that cardioembolic strokes are associated with shorter clot lengths and lower clot burden than non-cardioembolic clots. Objective To report the relationship between stroke etiology, extracted clot area, and histological composition at each procedural pass. Methods As part of the multi-institutional RESTORE Registry, the Martius Scarlett Blue stained histological composition and extracted clot area of 612 per-pass clots retrieved from 441 patients during mechanical thrombectomy procedures were quantified. Correlations with clinical and procedural details were investigated. Results Clot composition varied significantly with procedural passes; clots retrieved in earlier passes had higher red blood cell content (H4=11.644, p=0.020) and larger extracted clot area (H4=10.730, p=0.030). Later passes were associated with significantly higher fibrin (H4=12.935, p=0.012) and platelets/other (H4=15.977, p=0.003) content and smaller extracted clot area. Large artery atherosclerotic (LAA) clots were significantly larger in the extracted clot area and more red blood cell-rich than other etiologies in passes 1–3. Cardioembolic and cryptogenic clots had similar histological composition and extracted clot area across all procedural passes. Conclusion LAA clots are larger and associated with a large red blood cell-rich extracted clot area, suggesting soft thrombus material. Cardioembolic clots are smaller in the extracted clot area, consistent in composition and area across passes, and have higher fibrin and platelets/other content than LAA clots, making them stiffer clots. The per-pass histological composition and extracted clot area of cryptogenic clots are similar to those of cardioembolic clots, suggesting similar formation mechanisms.

Abstract Background: Most clots retrieved from patients with acute ischemic stroke are ‘red’ in color and are predominantly composed of red blood cells and fibrin. ‘White’ clots represent a less common entity and their histological composition is largely unknown.The aim of this study was to investigate the composition, imaging and procedural characteristics of ‘white’ clots retrieved by mechanical thrombectomy.Materials and Methods:Nineteen ‘white’ thrombi selected by visual inspection from 293 cases were collected as part of the multi-institutional RESTORE registry. Non-contrast computed tomography (NCCT), histological and immunohistochemical analyses were performed. Components were quantified using Orbit Image Analysis.Results:Quantification of Martius Scarlett Blue stain identified platelets/other as the major component in ‘white’ clots’ (63%) followed by fibrin (26%), red blood cells (7%) and white blood cells (4%). ‘White’ clots presented significantly more platelets/other and less red blood cells compared to the ‘red’ clots which showed a mean of 23% and 44%, respectively. The mean platelet (CD42b) content in ‘white’ clots was 43%; von Willebrand Factor (vWF) mean expression was 38%.Collagen and calcification were associated in one case. Fatty acid binding protein 4 was expressed in two cases.‘White’ clots were also significantly smaller (9.5 versus 12 mm) and less hyperdense (52 versus 61 Hounsfield Units) on NCCT compared to the other cases.Conclusions:‘White’ clots represented 6% of our cohort and are platelet and vWF-rich. Calcification, collagen and adipocytes were found occasionally. ‘White’ clots differ from other clots in composition, size and density on NCCT.

Background To assess if leukoaraiosis severity is associated with outcome in patients with acute ischemic stroke (AIS) following endovascular thrombectomy, and to propose a leukoaraiosis-related modification to the ASPECTS score. Methods A retrospective review was completed of AIS patients that underwent mechanical thrombectomy for anterior circulation large vessel occlusion. The primary outcome measure was 90-day mRS. A proposed Leukoaraiosis-ASPECTS (“L-ASPECTS”) was calculated by subtracting from the traditional ASPECT based on leukoaraiosis severity (1 point subtracted if mild, 2 if moderate, 3 if severe). L-ASEPCTS score performance was validated using a consecutive cohort of 75 AIS LVO patients. Results 174 patients were included in this retrospective analysis: average age: 68.0±9.1. 28 (16.1%) had no leukoaraiosis, 66 (37.9%) had mild, 62 (35.6%) had moderate, and 18 (10.3%) had severe. Leukoaraiosis severity was associated with worse 90-day mRS among all patients (P=0.0005). Both L-ASPECTS and ASPECTS were associated with poor outcomes, but the area under the curve (AUC) was higher with L-ASPECTS (P<0.0001 and AUC=0.7 for L-ASPECTS; P=0.04 and AUC=0.59 for ASPECTS). In the validation cohort, the AUC for L-ASPECTS was 0.79 while the AUC for ASPECTS was 0.70. Of patients that had successful reperfusion (mTICI 2b/3), the AUC for traditional ASPECTS in predicting good functional outcome was 0.80: AUC for L-ASPECTS was 0.89. Conclusions Leukoaraiosis severity on pre-mechanical thrombectomy NCCT is associated with worse 90-day outcome in patients with AIS following endovascular recanalization, and is an independent risk factor for worse outcomes. A proposed L-ASPECTS score had stronger association with outcome than the traditional ASPECTS score.

Abstract The severe acute respiratory syndrome coronavirus 2 pandemic of 2019 to 2020 has resulted in multiple hospitalizations, deaths, and economic hardships worldwide. Although respiratory involvement in patients with coronavirus disease 2019 ( COVID ‐19) is well known, the potential cardiovascular and cerebrovascular manifestations are less understood. We performed a PubMed and Google Scholar search and reviewed relevant literature on COVID ‐19 and cardiovascular system involvement. Severe acute respiratory syndrome coronavirus 2 possesses high affinity for angiotensin‐converting enzyme 2 receptor, which is highly concentrated in the lungs and cardiovascular tissue, thereby provoking concern for cardiovascular involvement in COVID ‐19 cases. Preexisting cardiovascular and cerebrovascular disease has been shown in previous reports to be a risk factor for severe infection. On the basis of our review of published studies, COVID ‐19 patients may be more likely to experience acute cardiac injury, arrhythmia, coagulation defects, and acute stroke and are likely to have poorer outcomes as a result. As the COVID ‐19 pandemic continues, more data about potential cardiovascular and cerebrovascular manifestations of the disease are required.