Abstract TP214: 3D-Electron Microscopy for the Analysis of the Microstructure of Acute Ischemic Stroke Clots

Introduction: Characterization of acute ischemic stroke thrombi has typically focused on the two dimensional (2D) histological characterization of the thrombus. Little is known about the three dimensional (3D) structure of these occlusive thrombi. Electron Microscopy (EM) can be used to obtain 3D information about the organization of clot components. Individual structures can be segmented and qualitative and quantitative information obtained from the clots. Methods: Following IRB approval from Mayo Clinic, acute ischemic stroke clot samples were collected from 10 patients treated at Mayo Clinic. Samples were immediately fixed in fresh modified Trumps fixative solution. A representative fragment of clot was taken and split longitudinally into two pieces; one piece was sent for 3D-EM analysis and the other for histological processing and analysis. Hematoxylin and eosin stain (H&E) and Martius Scarlett Blue (MSB) histological stains were used for conventional histopathology evaluation and components analysis. Immunohistochemical (IHC) staining using anti-CD42b (Platelets) was applied to confirm the presence of platelets in each clot. Serial block-face scanning electron microscopy was used to generate high-resolution three-dimensional images. Results: The 2D morphological features of the clot were identified using H&E, MSB and anti-CD42b staining. The 3D organization of thrombi varies greatly, both within and between clots depending on the constituents. Red Blood Cell-rich areas are mainly composed of Red Blood Cells packaged tightly together, with a small number of Fibrin strands interwoven between the cells. Fibrin-rich areas are characterized by dense networks of fibrin strands along with platelets and White Blood Cells with some sparse Red Blood Cells present. Platelet-rich areas are composed of large volumes of de-granulated platelets, some fibrin stands and white blood cells and an absence of Red Blood Cells. Conclusions: 3D electron microscopy can provide important information on the organization of components within thrombi. This could provide key information on the age and etiology of the thrombus. In addition, it may help to inform thrombolytic treatment and medical device design.

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Characterization of the ‘White’ Appearing Clots that Cause Acute Ischemic Stroke

10.21203/rs.3.rs-45700/v1 ◽

2020 ◽

Author(s):

Oana Madalina Mereuta ◽

Seán Fitzgerald ◽

Rosanna Rossi ◽

Andrew Douglas ◽

Abhay Pandit ◽

...

Keyword(s):

Ischemic Stroke ◽

Red Blood Cells ◽

Acute Ischemic Stroke ◽

Blood Cells ◽

White Blood Cells ◽

Fatty Acid Binding ◽

Blue Stain ◽

Von Willebrand ◽

Willebrand Factor

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.

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High-resolution scanning electron microscopy for the analysis of three-dimensional ultrastructure of clots in acute ischemic stroke

Journal of NeuroInterventional Surgery ◽

10.1136/neurintsurg-2020-016709 ◽

2020 ◽

pp. neurintsurg-2020-016709

Author(s):

Oana Madalina Mereuta ◽

Seán Fitzgerald ◽

Trace A Christensen ◽

Adam L Jaspersen ◽

Daying Dai ◽

...

Keyword(s):

Electron Microscopy ◽

Scanning Electron Microscopy ◽

Ischemic Stroke ◽

Acute Ischemic Stroke ◽

Blood Cells ◽

White Blood Cells ◽

Three Dimensional ◽

Ultrastructural Organization ◽

Thrombolytic Treatment ◽

Scanning Electron

BackgroundCharacterization 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).MethodsAs 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.ResultsQuantification 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.Conclusions3D-SEM provides novel and potentially clinically relevant information on clot components and ultrastructure which may help to inform thrombolytic treatment and medical device design.

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Abstract TMP26: Existence of Neutrophil Extracellular Traps in Arterial Thrombi from Patients with Acute Ischemic Stroke

Stroke ◽

10.1161/str.48.suppl_1.tmp26 ◽

2017 ◽

Vol 48 (suppl_1) ◽

Author(s):

Wei Li ◽

Huan Wang ◽

Wuwei Feng ◽

Meng Zhang

Keyword(s):

Electron Microscopy ◽

Ischemic Stroke ◽

Acute Ischemic Stroke ◽

White Blood Cells ◽

Neutrophil Extracellular Traps ◽

Immunofluorescence Staining ◽

Large Artery ◽

Extracellular Traps ◽

Arterial Thrombus ◽

Hematoxylin Eosin

Introduction: Neutrophil extracellular traps (NETs) are composed mainly of strands of filamentous DNA and nuclear proteins, such as chromatin or isoforms of histone and secretable neutrophil granular proteins. Recent studies have shown that NETs existed in the venous thrombi and might function as a scaffold and had implication for thrombolytic treatments. Hypothesis: NETs also exists in cerebral arterial thrombus collected from patients with acute ischemic stroke(AIS). Methods: Ten arterial thrombi were collected from 10 AIS patients (33-78 years old, 4 females) who were treated by endovascular therapy (eight of them accepted alteplase thrombolysis firstly)within 8 hours after symptoms onset. Hematoxylin-eosin (HE) staining, immunofluorescence staining (including anti-histone H3 and Hoechst 33342 which label DNA) and electron microscopy were performed to identify the existence of fibrin and/or NETs in thrombus. Results: There were 4 thrombi from middle cerebral artery, 3 from internal carotid artery and 3 from basilar artery. Cardioembolism were considered as etiology for 5 patients and large artery atherosclerosis was the etiology for another 5 patients. HE staining showed that large amounts of fibrin and white blood cells in all ten cerebral arterial thrombi. NETs structures were also identified in 10/10 cerebral arterial thrombi by immunofluorescence staining. Furthermore, the existence of neutrophil-released DNA network together with fibrin was confirmed using electron microscopy in all 10 thrombi. Conclusion: Our results directly demonstrated that NETs do exist in the arterial thrombi from patients with AIS. they may serve as another structural component in addition to fibrin in both cardiogenic and artery atherosclerotic thrombi. NETs can be a new potential target for the recanalization treatment. Keyword: Neutrophil extracellular traps (NETs); arterial thrombus; Acute ischemic stroke

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Reliable assessment of bone marrow and bone marrow concentrates using automated hematology analyzer

Regenerative Medicine ◽

10.2217/rme-2018-0173 ◽

2019 ◽

Vol 14 (7) ◽

pp. 639-646 ◽

Cited By ~ 2

Author(s):

Venkata P Mantripragada ◽

Nicolas S Piuzzi ◽

Jaiben George ◽

Wesley Bova ◽

Mitchell Ng ◽

...

Keyword(s):

Bone Marrow ◽

Red Blood Cells ◽

Blood Cells ◽

White Blood Cells ◽

Limiting Factor ◽

Cell Therapies ◽

Reliable Assessment ◽

Hematology Analyzer ◽

Automated Hematology Analyzer

Aim: A limiting factor in advancement of bone marrow based cell therapies is the lack of characterization of cell products delivered to patients. Methods: Using an automated hematology analyzer that can be implemented in clinical setting, the composition of bone marrow aspirates (n = 17 patients) and bone marrow concentrates (n = 12 patients) were assessed. ICC estimates were calculated for measuring reliability. Results: Bone marrow aspirates assessment resulted in excellent reliability for determining white blood cells (ICC – 0.96; 95% CI: 0.92–0.99), red blood cells (ICC – 0.9; 95% CI: 0.77–0.96), platelets (ICC – 0.93; 95% CI: 0.85–0.97) composition. Bone marrow concentrate assessment resulted in excellent reliability for determining white blood cells (ICC – 0.97; 95% CI: 0.93–0.99), platelets (ICC – 0.95; 95% CI: 0.89–0.99) and moderate reliability for red blood cells (ICC – 0.66; 95% CI: 0.36–0.87) composition. Conclusion: Modern automated hematology analyzers could assist to better characterize the cell therapy products to provide reliable and consistent outcomes.

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The role of diabetes mellitus on the thrombus composition in patients with acute ischemic stroke

Interventional Neuroradiology ◽

10.1177/1591019919896940 ◽

2020 ◽

Vol 26 (3) ◽

pp. 329-336 ◽

Cited By ~ 1

Author(s):

Gengfan Ye ◽

Qun Gao ◽

Peng Qi ◽

Junjie Wang ◽

Shen Hu ◽

...

Keyword(s):

Diabetes Mellitus ◽

Ischemic Stroke ◽

Red Blood Cells ◽

Acute Ischemic Stroke ◽

Von Willebrand Factor ◽

Blood Cells ◽

Smoking History ◽

Diabetic Patients ◽

Von Willebrand ◽

Willebrand Factor

Purpose Diabetes mellitus indicated poor clinical prognosis for patients with acute ischemic stroke. Furthermore, diabetes mellitus could also impact the hemostatic system, while its influence on the histological composition of thrombus is unclear. Methods Consecutive patients with retrieved clots were included. Histologic staining for thrombus included hematoxylin and eosin, Martius Scarlet Blue, immunohistochemistry for von Willebrand factor. The differences in clot composition were compared according to diabetes mellitus history or hyperglycemia (≥7.8 mmol/L) on admission. Results A total of 52 patients were included; half of them were diagnosed as diabetes mellitus previously. Diabetic patients showed higher serum glucose on admission (8.90 vs. 7.40, p = 0.012). The baseline characteristics (expect smoking history and thrombus location), procedural, and clinical outcomes were similar between diabetic patients and nondiabetic patients. As for histologic composition, thrombus in patients with diagnosed diabetes mellitus had more fibrin (44.2% vs. 28.3%, p = 0.004) and fewer red blood cells (26.0% vs. 42.9%, p = 0.013) and equivalent content of platelets (24.0% vs. 21.5%, p = 0.694) and von Willebrand factor (0.041 vs. 0.031, p = 0.234) than patients without diabetes mellitus. However, there was no statistical difference in the content of red blood cells (41.6% vs. 27.3%, p = 0.105), fibrin (37.6% vs. 34.3%, p = 0.627), platelets (21.2% vs. 24.2%, p = 0.498), and von Willebrand factor (0.038 vs. 0.034, p = 0.284) between patients with or without hyperglycemia on admission. Conclusion Clots in diabetic patients had more fibrin and fewer erythrocyte components compared with patients without diabetes mellitus, while hyperglycemia on admission did not show association with clot composition. Further studies are needed to confirm these results.

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Dynamic Change of Neutrophil to Lymphocyte Ratios and Infection in Patients with Acute Ischemic Stroke

Current Neurovascular Research ◽

10.2174/1567202617666200408091131 ◽

2020 ◽

Vol 17 (3) ◽

pp. 294-303 ◽

Cited By ~ 1

Author(s):

Lu Wang ◽

Wen Guo ◽

Changyi Wang ◽

Xue Yang ◽

Zilong Hao ◽

...

Keyword(s):

Ischemic Stroke ◽

Acute Ischemic Stroke ◽

Blood Cells ◽

Temporal Change ◽

Dynamic Change ◽

White Blood Cells ◽

Secondary Outcome ◽

Stroke Patients ◽

Time Of Infection ◽

Interaction Term

Background: Neutrophil to lymphocyte ratio (NLR) on admission was reported to be a predictor of pneumonia after stroke. The aim of this study was to investigate the association between the temporal change of NLR and post-stroke infection and whether infection modified the effect of NLR on the outcome. Methods: We enrolled patients with acute ischemic stroke within 24 h after onset. The blood was collected on admission, day 1, 3, 7 after admission to detect white blood cells (WBC), neutrophils, and lymphocytes. Primary outcomes included pneumonia, urinary tract infection (UTI), other infection, and the secondary outcome was 3-month death. Results: Of 798 stroke patients, 299 (37.66%) developed infection with 240 (30.23%) pneumonia, 78 (9.82%) UTI, and 9 (1.13%) other infection. The median time of infection occurrence was 48 h (interquartile range 27-74 h) after onset. NLR reached to the peak at 36 h. For all outcomes, NLR at 36 h after stroke had the highest predictive value than WBC, neutrophil, lymphocyte. NLR was independently associated with the presence of any infection (odds ratio [OR] 1.11, 95% confidence interval [CI] 1.05-1.17), pneumonia (OR 1.12, 95%CI 1.05-1.19), but not UTI (OR 0.95, 95%CI 0.89-1.01). Adding infection or the interaction term did not substantially change the OR of NLR predicting 3-month death (OR 1.09, 95%CI 1.01, 1.17). Conclusion: Increased NLR around 36 h after stroke was a predictor of infection in patients with acute ischemic stroke. The increased NLR value was associated with a higher risk of 3-month death, which was independent of poststroke infection.

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Abstract WP108: Novel Human Acute Ischemic Stroke Blood Clot Analogues for in-vitro Testing

Stroke ◽

10.1161/str.51.suppl_1.wp108 ◽

2020 ◽

Vol 51 (Suppl_1) ◽

Author(s):

Seán Fitzgerald ◽

Daying Dai ◽

Andrew S Douglas ◽

Oana M Mereuta ◽

Thomas Caracena ◽

...

Keyword(s):

Ischemic Stroke ◽

Red Blood Cells ◽

Acute Ischemic Stroke ◽

Human Blood ◽

Whole Blood ◽

Blood Cells ◽

Blood Clot ◽

Buffy Coat

Introduction: Previous studies have successfully created blood clot analogues for In-vitro testing using animal blood. Blood components vary greatly among species and thus, creating clot analogues with human blood is likely a more accurate representation of thrombi formed in the human vasculature. We present a novel method of creating clot analogues from human blood and platelets that mimic the process by which clots form In-vivo . Methods: Following IRB approval from Mayo Clinic, human whole blood and platelets donations were obtained from the Blood Transfusion service. The whole blood was centrifuged at 1,200RPM for 20 minutes to separate it into its constituents. Plasma was removed and the remaining Red Blood Cells and Buffy Coat were mixed together by inverting. A total of 12 clot analogues were created with varying concentrations of components; Red Blood cells/Buffy Coat, Plasma and Platelets. Thrombin was added first to stimulate platelets activation for a total of 5 mins whilst continuously mixing by inversion. The RBC/WBC mixture was added next followed by CaCl2. The mixture was then quickly drawn into a 3cc syringe and spun overnight at 20RPM at room temperature to mimic dynamic flow conditions. Macro-photographs were taken to display the variation in texture and color between different clot analogue types. The clots were then fixed in 10% neutral buffered formalin for 24 hours prior to being processed. Histopathological analysis was performed using Hematoxylin and Eosin (H&E) and Martius Scarlet Blue (MSB) staining to confirm clot composition. Results: Red Blood cell-rich, Fibrin-rich, Platelet-rich and mixed clot analogues that accurately mimic clots retrieved from Acute Ischemic Stroke Patients were created. The range of histopathological compositions of the clot analogues is similar to that of the clinical samples. Conclusions: The addition and activation of platelets is key to creating accurate clot analogues for In-vitro testing. Spinning the clots is important to prevent natural sedimentation and mimic the In-vivo situation.

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Correlation of Neutrophil to Lymphocyte Ratio with Expression of Neutrophil Extracellular Traps Within Stroke Emboli

Interventional Neuroradiology ◽

10.1177/15910199211065530 ◽

2021 ◽

pp. 159101992110655

Author(s):

Jorge Arturo Larco ◽

Mehdi Abbasi ◽

Sarosh Irfan Madhani ◽

Madalina Oana Mereuta ◽

Yang Liu ◽

...

Keyword(s):

Ischemic Stroke ◽

Acute Ischemic Stroke ◽

Blood Cells ◽

White Blood Cells ◽

Neutrophil Extracellular Traps ◽

Vessel Occlusion ◽

Average Percentage ◽

Neutrophil Lymphocyte Ratio ◽

Lymphocyte Ratio ◽

Extracellular Traps

Background & Purpose It has been hypothesized that circulating neutrophils have a direct correlation with the composition of emboli in acute ischemic stroke (AIS). The aim of this study is to evaluate the association between neutrophil-lymphocyte ratio (NLR) in peripheral blood and the expression of neutrophil extracellular traps (NETs) within stroke emboli. Methods Consecutive patients with acute ischemic stroke (AIS) due to large vessel occlusion (LVO) that underwent mechanical thrombectomy (MT) were included. Patients were divided into two groups based on NLR median value. Retrieved thrombi were histologically analyzed using Martius Scarlett Blue (MSB) for main thrombus components including red blood cells (RBCs), white blood cells (WBCs), fibrin and platelet. Immunohistochemistry staining for von Willebrand Factor (vWF) and anti-citrullinated H3 (H3Cit; NETs marker) was also performed. Results Samples from a total of 84 patients were included. The average percentage of RBCs, WBCs, fibrin, platelet, H3Cit, and vWF components in thrombi were 45.1%, 3.5%, 21.8%, 29.6%, 19.7% and 14.8% respectively. When stratifying by NLR group [low (≤3.94) versus high (>3.95)], high NLR group had significantly more WBCs (4.5%), fibrin (24.2%), H3Cit (22.7%) and vWF (17.1%) thrombus fractions compared to low NLR group. Additionally, RBC content (38.8%) was lower in the high NLR group. Conclusions NLR is correlated with the amounts of WBCs, fibrin, NETs and vWF within the thrombi retrieved from AIS patients due to LVO.

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Thrombus Structural Composition in Cardiovascular Disease

Arteriosclerosis Thrombosis and Vascular Biology ◽

10.1161/atvbaha.120.315754 ◽

2021 ◽

Author(s):

Ghadir Alkarithi ◽

Cédric Duval ◽

Yu Shi ◽

Fraser L. Macrae ◽

Robert A.S. Ariëns

Keyword(s):

Myocardial Infarction ◽

Cardiovascular Disease ◽

Ischemic Stroke ◽

Venous Thromboembolism ◽

Red Blood Cells ◽

Acute Ischemic Stroke ◽

Blood Cells ◽

Laser Scanning ◽

Thrombus Formation ◽

Ischemic Time

Thrombosis is a major complication of cardiovascular disease, leading to myocardial infarction, acute ischemic stroke (AIS), or venous thromboembolism. Thrombosis occurs when a thrombus forms inside blood vessels disrupting blood flow. Developments in thrombectomy to remove thrombi from vessels have provided new opportunities to study thrombus composition which may help to understand mechanisms of disease and underpin improvements in treatments. We aimed to review thrombus compositions, roles of components in thrombus formation and stability, and methods to investigate thrombi. Also, we summarize studies on thrombus structure obtained from cardiovascular patients and animal models. Thrombi are composed of fibrin, red blood cells, platelets, leukocytes, and neutrophil extracellular traps. These components have been analyzed by several techniques, including scanning electron microscopy, laser scanning confocal microscopy, histochemistry, and immunohistochemistry; however, each technique has advantages and limitations. Thrombi are heterogenous in composition, but overall, thrombi obtained from myocardial infarction are composed of mainly fibrin and other components, including platelets, red blood cells, leukocytes, and cholesterol crystals. Thrombi from patients with acute ischemic stroke are characterized by red blood cell- and platelet-rich regions. Thrombi from patients with venous thromboembolism contain mainly red blood cells and fibrin with some platelets and leukocytes. Thrombus composition from patients with myocardial infarction is influenced by ischemic time. Animal thrombosis models are crucial to gain further mechanistic information about thrombosis and thrombus structure, with thrombi being similar in composition compared with those from patients. Further studies on thrombus composition and function are key to improve treatment and clinical outcome of thrombosis.

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Ischemic Stroke: Histological Thrombus Composition and Pre-Interventional CT Attenuation Are Associated with Intervention Time and Rate of Secondary Embolism

Cerebrovascular Diseases ◽

10.1159/000481578 ◽

2017 ◽

Vol 44 (5-6) ◽

pp. 344-350 ◽

Cited By ~ 29

Author(s):

Peter B. Sporns ◽

Uta Hanning ◽

Wolfram Schwindt ◽

Aglae Velasco ◽

Boris Buerke ◽

...

Keyword(s):

Ischemic Stroke ◽

Red Blood Cells ◽

Blood Cells ◽

Medical Center ◽

White Blood Cells ◽

Unaffected Side ◽

Time Frequency ◽

Ct Attenuation ◽

The Impact ◽

Interventional Ct

Background and Purpose: The introduction of stent retrievers has made the complete extraction and histological analysis of human thrombi possible. A number of large randomized trials have proven the efficacy of thrombectomy for ischemic stroke; however, thrombus composition could have an impact on the efficacy and risk of the intervention. We therefore investigated the impact of histologic thrombus features on interventional outcome and procedure-related embolisms. For a pre-interventional estimation of histologic features and outcome parameters, we assessed the pre-interventional CT attenuation of the thrombi. Methods: We prospectively included all consecutive patients with occlusion of the middle cerebral artery who underwent thrombectomy between December 2013 and February 2016 at our university medical center. Samples were histologically analyzed (H&E, Elastica van Gieson, Prussian blue); additionally, immunohistochemistry for CD3, CD20, and CD68/KiM1P was performed. Main thrombus components (fibrin, erythrocytes, and white blood cells) were determined and compared to intervention time, frequency of secondary embolisms, as well as additional clinical and interventional parameters. Additionally, we assessed the pre-interventional CT attenuation of the thrombi in relation to the unaffected side (rHU) and their association with histologic features. Results: One hundred eighty patients were included; of these, in 168 patients (93.4%), complete recanalization was achieved and 27 patients (15%) showed secondary embolism in the control angiogram. We observed a significant association of high amounts of fibrin (p < 0.001), low percentage of red blood cells (p < 0.001), and lower rHU (p < 0.001) with secondary embolism. Higher rHU values were significantly associated with higher amounts of fibrin (p ≤ 0.001) and low percentage of red blood cells (p ≤ 0.001). Additionally, high amounts of fibrin were associated with longer intervention times (p ≤ 0.001), whereas thrombi with high amounts of erythrocytes correlated with shorter intervention times (p ≤ 0.001). ROC analysis revealed reliable prediction of secondary embolisms for low rHU (AUC = 0.746; p ≤ 0.0001), low amounts of RBC (AUC = 0.764; p ≤ 0.0001), and high amounts of fibrin (AUC = 0.773; p ≤ 0.0001). Conclusions: Fibrin-rich thrombi with low erythrocyte percentage are significantly associated with longer intervention times. Embolisms in the thrombectomy process occur more often in thrombi with a small fraction of red blood cells and a low CT-density, suggesting a higher fragility of these thrombi.

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