A case report of thrombolysis resistance: thrombus ultrastructure in an ischemic stroke patient

Li, Ye; Wang, Heying; Zhao, Lili; Jian, Yating; Dang, Meijuan; Jiang, Yu; Zhang, Yiheng; Zhang, Lei; Wang, Huqing; Zhang, Ru; Chen, Mingxia; Zhang, Guilian

doi:10.1186/s12883-020-01706-3

Cited by 9 publications

(10 citation statements)

References 13 publications

(14 reference statements)

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“…We were able to section the specimens in the longitudinal or transverse direction. SEM images showed that the platelets were tightly packed in the clot with a density of 0.1 platelets/µm 2 , indicating that the 1.23 billion platelets were aggregated in the SIPA clot, which is significantly different from previous images of RBC-rich blood clots [14][15][16] . Spherical platelets were found in the SEM images, and its morphology was similar to the platelets found in the ultradensely packed region of mice puncture injury model by Tomaiuolo, et al 28 .…”

Section: Discussioncontrasting

confidence: 87%

“…Previous approaches using in vivo animal models with intravital fluorescence imaging 13 had a spatial resolution limit that impedes the investigation of the micro-structures of blood clots 5 . In contrast, thrombi extracted during a thrombectomy can subsequently be imaged via SEM [14][15][16] or microscopy of histologic sections 10,17 . However, this thrombectomy-based approach has weaknesses.…”

Section: Introductionmentioning

confidence: 99%

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Structure of shear-induced platelet aggregated clot formed in an in vitro arterial thrombosis model

Kim

2022

Blood Advances

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The structure of occlusive arterial thrombi is described in this paper. Macroscopic thrombi are made from whole blood in a collagen-coated, large-scale stenosis with high shear flow conditions similar to an atherosclerotic artery. The millimeter-sized thrombi are harvested for histology and scanning electron microscopy. Histological images showed 3 distinctive structures of the thrombus. A) The upstream region showed string-like platelet aggregates growing out from the wall to protrude into the central lumen, while RBCs were trapped between the strings. The strings were >10x as long as they were wide and reached out to join the strings from the opposite wall. B) Near the apex, the platelet strings coalesced into a dense mass with microchannels that effectively occludes the lumen. C) In the expansion region, the thrombus ended abruptly with an annulus of free blood in the flow separation zone. Scanning electron microscopy showed dense clusters of spherical platelets upstream and downstream, with amorphous platelets in the occluded throat consistent with prior activation. The total clot is estimated to contain 1.23 billion platelets with pores on the order of 10-100 microns. The results reveal a complex structure of arterial thrombi that grow from their tips under high shear stress to bridge the 2.5 mm lumen quickly with VWF-platelet strings. The occlusion leaves many microchannels that allow some flow through the bulk of the thrombus. This architecture can create occlusion or hemostasis rapidly with minimal material, yet remain porous for potential delivery of lytic agents to the core of the thrombus.

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Section: Discussioncontrasting

confidence: 87%

Section: Introductionmentioning

confidence: 99%

Structure of shear-induced platelet aggregated clot formed in an in vitro arterial thrombosis model

Kim

2022

Blood Advances

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“…[21] The compaction of polyhedral RBC and modification of the fibrin network, together with other biological factors, have been previously shown to contribute to the rt-PA resistance. [19,22,23] Interestingly, we described a distinct fibrin organization in three clots (i.e., grid-like and sponge-like patterns) that are likely to be caused by the rt-PA therapy. The fact that we found two different patterns may be explained by the different regions analyzed and also by different exposure to rt-PA between these cases.…”

Section: Discussionmentioning

confidence: 81%

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

Mereuta

Fitzgerald

Christensen

et al. 2020

J NeuroIntervent Surg

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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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“…This was in stark contrast to the clearly identifiable RBCs, FBR fibers, and aggregated PLTs in the inner core. 63,107 Other ultrastructural studies showed morphologic features consistent with the presence of NETs, calcified deposits and cholesterol crystals in the clots. 44,99…”

Section: Thrombus Structure and Composition: Advanced Imaging And Histopathologymentioning

confidence: 93%

Clot Composition Analysis as a Diagnostic Tool to Gain Insight into Ischemic Stroke Etiology: A Systematic Review

et al. 2021

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Mechanical thrombectomy renders the occluding clot available for analysis. Insights into thrombus composition could help establish the stroke cause. We aimed to investigate the value of clot composition analysis as a complementary diagnostic tool in determining the etiology of large vessel occlusion (LVO) ischemic strokes (International Prospective Register of Systematic Reviews [PROSPERO] registration # CRD42020199436). Following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines, we ran searches on Medline (using the PubMed interface) and Web of Science for studies reporting analyses of thrombi retrieved from LVO stroke patients subjected to mechanical thrombectomy (January 1, 2006 to September 21, 2020). The PubMed search was updated weekly up to February 22, 2021. Reference lists of included studies and relevant reviews were hand-searched. From 1,714 identified studies, 134 eligible studies (97 cohort studies, 31 case reports, and six case series) were included in the qualitative synthesis. Physical, histopathological, biological, and microbiological analyses provided information about the gross appearance, mechanical properties, structure, and composition of the thrombi. There were non-unanimous associations of thrombus size, structure, and composition (mainly proportions of fibrin and blood formed elements) with the Trial of Org 10172 in Acute Stroke Treatment (TOAST) etiology and underlying pathologies, and similarities between cryptogenic thrombi and those of known TOAST etiology. Individual thrombus analysis contributed to the diagnosis, mainly in atypical cases. Although cohort studies report an abundance of quantitative rates of main thrombus components, a definite clot signature for accurate diagnosis of stroke etiology is still lacking. Nevertheless, the qualitative examination of the embolus remains an invaluable tool for diagnosing individual cases, particularly regarding atypical stroke causes.

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A case report of thrombolysis resistance: thrombus ultrastructure in an ischemic stroke patient

Cited by 9 publications

References 13 publications

Structure of shear-induced platelet aggregated clot formed in an in vitro arterial thrombosis model

Structure of shear-induced platelet aggregated clot formed in an in vitro arterial thrombosis model

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

Clot Composition Analysis as a Diagnostic Tool to Gain Insight into Ischemic Stroke Etiology: A Systematic Review

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