Current studies on clot characterization in acute ischemic stroke focus on fibrin and red blood cell composition. Few studies have examined platelet composition in acute ischemic stroke clots. We ...characterize clot composition using the Martius Scarlet Blue stain and assess associations between platelet density and CT density.
Histopathological analysis of the clots collected as part of the multi-institutional STRIP registry was performed using Martius Scarlet Blue stain and the composition of the clots was quantified using Orbit Image Analysis (www.orbit.bio) machine learning software. Prior to endovascular treatment, each patient underwent non-contrast CT (NCCT) and the CT density of each clot was measured. Correlations between clot components and clinical information were assessed using the χ
test.
Eighty-five patients were included in the study. The mean platelet density of the clots was 15.7% (2.5-72.5%). There was a significant correlation between platelet-rich clots and the absence of hyperdensity on NCCT, (ρ=0.321, p=0.003*, n=85). Similarly, there was a significant inverse correlation between the percentage of platelets and the mean Hounsfield Units on NCCT (ρ=-0.243, p=0.025*, n=85).
Martius Scarlet Blue stain can identify patients who have platelet-rich clots. Platelet-rich clots are isodense on NCCT.
Background and Purpose- Nearly 30% of large vessel occlusion acute ischemic stroke clots are from an unknown source. We assessed histological clot composition in a series of patients with large ...vessel occlusion and investigated correlations between clot composition and stroke pathogenesis. Methods- As part of the multi-institutional STRIP registry (Stroke Thromboembolism Registry of Imaging and Pathology), consecutive emboli retrieved during mechanical thrombectomy were stained using Martius Scarlett Blue and analyzed using machine learning software. We assessed proportions of red blood cells, fibrin, platelets, and white blood cells. Correlations between clot components and stroke pathogenesis (large artery atherosclerosis, cardioembolism, and stroke of undetermined pathogenesis) were assessed using SPSS22. Results- One hundred five patients were included. The proportion of platelet-rich clots (55.0% versus 21.2%; P=0.005) and percentage of platelet content (22.1±4.2% versus 13.9±14.2%; P=0.03) was significantly higher in the large artery atherosclerosis group compared with the cardioembolic group. The proportion of platelet-rich clots (50.0% versus 21.2%; P=0.024) was also significantly higher in the cryptogenic group compared with cardioembolic cases. Large artery atherosclerosis and cryptogenic cases had a similar proportion of platelet-rich clots (55.0% versus 50.0%; P=0.636). There was no significant difference between stroke pathogenesis and the other major clot components. Conclusions- High platelet content of emboli is associated with a large artery atherosclerosis etiology of large vessel occlusion.
We retrospectively evaluated the composition of retrieved clots from ischemic stroke patients to study the association between histological composition and stroke etiology METHODS: Consecutive ...patients enrolled in the Stroke Thromboembolism Registry of Imaging and Pathology (STRIP) were included in this study. All patients underwent mechanical thrombectomy and retrieved clots were sent to a central core lab for processing. Histological analysis was performed using martius scarlet blue (MSB) staining, and quantification for red blood cells (RBCs), white blood cells (WBCs), fibrin and platelets was performed using Orbit Image Software. A Wilcoxon test was used for continuous variables and χ
test for categorical variables.
1350 patients were included in this study. The overall rate of Thrombolysis In Cerebral Infarction (TICI) 2c/3 was 68%. 501 patients received tissue plasminogen activator (tPA) (37%). 267 patients (20%) had a large artery atherosclerosis (LAA) source, 662 (49%) a cardioembolic (CE) source, 301 (22%) were cryptogenic, and the remainder had other identifiable sources including hypercoagulable state or dissection. LAA thrombi had a higher mean RBC density (46±23% vs 42±22%, p=0.01) and a lower platelet density (24±18% vs 27±18%, p=0.03) than CE thrombi. Clots from dissection patients had the highest mean RBC density (50±24%) while clots from patients with a hypercoagulable state had the lowest mean RBC density (26±21%).
Our study found statistically significant but clinically insignificant differences between clots of CE and LAA etiologies. Future studies should emphasize molecular, proteomic and immunohistochemical characteristics to determine links between clot composition and etiology.
Several animal studies have demonstrated that mechanical thrombectomy (MT) for acute ischemic stroke (AIS) may cause vessel wall injury (VWI). However, the histological changes in human cerebral ...arteries following MT are difficult to determine.
To investigate the occurrence of VWI during MT by histological and immunohistochemical evaluation of AIS clots.
As part of the multicenter STRIP registry, 277 clots from 237 patients were analyzed using Martius Scarlett Blue stain and immunohistochemistry for CD34 (endothelial cells) and smooth muscle actin (smooth muscle cells).
MT devices used were aspiration catheters (100 cases), stentriever (101 cases), and both (36 cases). VWI was found in 33/277 clots (12%). There was no significant correlation between VWI and MT device. The degree of damage varied from grade I (mild intimal damage, 24 clots), to grade II (relevant intimal and subintimal damage, 3 clots), and III (severe injury, 6 clots). VWI clots contained significantly more erythrocytes (p=0.006*) and less platelets/other (p=0.005*) than non-VWI clots suggesting soft thrombus material.Thrombolysis correlated with a lower rate of VWI (p=0.04*). VWI cases showed a significantly higher number of passes (2 1-4 vs 1 1-3, p=0.028*) and poorer recanalization outcome (p=0.01*) than cases without VWI.
Histological markers of VWI were present in 12% of AIS thrombi, suggesting that VWI might be related to MT. VWI was associated with soft thrombus consistency, higher number of passes and poorer revascularization outcome. There was no significant correlation between VWI and MT device.
Compositional and structural features of retrieved clots by thrombectomy can provide insight into improving the endovascular treatment of ischemic stroke. Currently, histological analysis is limited ...to quantification of compositions and qualitative description of the clot structure. We hypothesized that heterogeneous clots would be prone to poorer recanalization rates and performed a quantitative analysis to test this hypothesis.
We collected and did histology on clots retrieved by mechanical thrombectomy from 157 stroke cases (107 achieved first-pass effect (FPE) and 50 did not). Using an in-house algorithm, the scanned images were divided into grids (with sizes of 0.2, 0.3, 0.4, 0.5, and 0.6 mm) and the extent of non-uniformity of RBC distribution was computed using the proposed spatial heterogeneity index (SHI). Finally, we validated the clinical significance of clot heterogeneity using the Mann-Whitney test and an artificial neural network (ANN) model.
For cases with FPE, SHI values were smaller (0.033 vs 0.039 for grid size of 0.4 mm, P=0.028) compared with those without. In comparison, the clot composition was not statistically different between those two groups. From the ANN model, clot heterogeneity was the most important factor, followed by fibrin content, thrombectomy techniques, red blood cell content, clot area, platelet content, etiology, and admission of intravenous tissue plasminogen activator (IV-tPA). No statistical difference of clot heterogeneity was found for different etiologies, thrombectomy techniques, and IV-tPA administration.
Clot heterogeneity can affect the clot response to thrombectomy devices and is associated with lower FPE. SHI can be a useful metric to quantify clot heterogeneity.
Mechanical thrombectomy (MT) has become standard for large vessel occlusions, but rates of complete recanalization are suboptimal. Previous reports correlated radiographic signs with clot composition ...and a better response to specific techniques. Therefore, understanding clot composition may allow improved outcomes.
Clinical, imaging, and clot data from patients enrolled in the STRIP Registry from September 2016 to September 2020 were analyzed. Samples were fixed in 10% phosphate-buffered formalin and stained with hematoxylin-eosin and Martius Scarlett Blue. Percent composition, richness, and gross appearance were evaluated. Outcome measures included the rate of first-pass effect (FPE, modified Thrombolysis in Cerebral Infarction 2c/3) and the number of passes.
A total of 1430 patients of mean±SD age 68.4±13.5 years (median (IQR) baseline National Institutes of Health Stroke Scale score 17.2 (10.5-23), IV-tPA use 36%, stent-retrievers (SR) 27%, contact aspiration (CA) 27%, combined SR+CA 43%) were included. The median (IQR) number of passes was 1 (1-2). FPE was achieved in 39.3% of the cases. There was no association between percent histological composition or clot richness and FPE in the overall population. However, the combined technique resulted in lower FPE rates for red blood cell (RBC)-rich (P<0.0001), platelet-rich (P=0.003), and mixed (P<0.0001) clots. Fibrin-rich and platelet-rich clots required a higher number of passes than RBC-rich and mixed clots (median 2 and 1.5 vs 1, respectively; P=0.02). CA showed a trend towards a higher number of passes with fibrin-rich clots (2 vs 1; P=0.12). By gross appearance, mixed/heterogeneous clots had lower FPE rates than red and white clots.
Despite the lack of correlation between clot histology and FPE, our study adds to the growing evidence supporting the notion that clot composition influences recanalization treatment strategy outcomes.
Platelets and von Willebrand factor (vWF) are key components of acute ischemic stroke (AIS) emboli. We aimed to investigate the CD42b (platelets)/vWF expression, its association with stroke etiology ...and the impact these components may have on the clinical/procedural parameters.
CD42b/vWF immunostaining was performed on 288 emboli collected as part of the multicenter STRIP Registry. CD42b/VWF expression and distribution were evaluated. Student's t-test and χ
test were performed as appropriate.
The mean CD42b and VWF content in clots was 44.3% and 21.9%, respectively. There was a positive correlation between platelets and vWF (r=0.64, p<0.001**). We found a significantly higher vWF level in the other determined etiology (p=0.016*) and cryptogenic (p=0.049*) groups compared with cardioembolic etiology. No significant difference in CD42b content was found across the etiology subtypes. CD42b/vWF patterns were significantly associated with stroke etiology (p=0.006*). The peripheral pattern was predominant in atherosclerotic clots (36.4%) while the clustering (patchy) pattern was significantly associated with cardioembolic and cryptogenic origin (66.7% and 49.8%, respectively). The clots corresponding to other determined etiology showed mainly a diffuse pattern (28.1%). Two types of platelets were distinguished within the CD42b-positive clusters in all emboli: vWF-positive platelets were observed at the center, surrounded by vWF-negative platelets. Thrombolysis correlated with a high platelet content (p=0.03*). vWF-poor and peripheral CD42b/vWF pattern correlated with first pass effect (p=0.03* and p=0.04*, respectively).
The vWF level and CD42b/vWF distribution pattern in emboli were correlated with AIS etiology and revascularization outcome. Platelet content was associated with response to thrombolysis.
Background and aim
Mechanical thrombectomy (MT) for large vessel occlusion often requires multiple passes to retrieve the entire thrombus load. In this multi-institutional study we sought to examine ...the composition of thrombus fragments retrieved with each pass during MT.
Methods
Patients who required multiple passes during thrombectomy were included. Histopathological evaluation of thrombus fragments retrieved from each pass was performed using Martius Scarlet Blue staining and the composition of each thrombus component including RBC, fibrin and platelet was determined using image analysis software.
Results
154 patients underwent MT and 868 passes was performed which resulted in 263 thrombus fragments retrieval. The analysis of thrombus components per pass showed higher RBC, lower fibrin and platelet composition in the pass 1 and 2 when compared to pass 3 and passes 4 or more combined (P values <0.05). There were no significant differences between thrombus fragments retrieved in pass 1 and pass 2 in terms of RBC, WBC, fibrin, and platelet composition (P values >0.05). Similarly, when each composition of thrombus fragments retrieved in pass 3 and passes 4 or more combined were compared with each other, no significant difference was noted (P values >0.05).
Conclusion
Our findings confirm that thrombus fragments retrieved with each pass differed significantly in histological content. Fragments in the first passes were associated with lower fibrin and platelet composition compared to fragments retrieved in passes three and four or higher. Also, thrombus fragments retrieved after failed pass were associated with higher fibrin and platelet components.
Introduction
The AXERA 2 low-angle vascular access device utilizes a dual arteriotomy mechanism in which the standard access tract is compressed by a vascular sheath inserted over the second, ...low-angle tract. It is unknown whether this device could be effectively used with 21-gauge micropuncture access, as the micropuncture introducer makes a larger arteriotomy than the 19-gauge needle provided with the AXERA 2 system.
Materials and Methods
A retrospective review was performed on 189 patients who underwent common femoral artery access for diagnostic cerebrovascular angiography using either combined micropuncture and AXERA 2 access or standard access with manual pressure hemostasis. Demographic and procedural data were reviewed along with complications related to vascular access and times to bed elevation, ambulation and discharge.
Results
Combined micropuncture and AXERA 2 access was performed on 110 patients and 79 patients had standard access. The AXERA device was successfully used in 91.8% of the cases. Demographic data, anticoagulant use and sheath sizes were similar between both subsets. Use of the AXERA 2 was associated with two bleeding complications (1.8%) compared with 10 (12.7%) with manual pressure hemostasis alone. Institution-specific protocol allowed shorter mean manual compression time, as well as shorter times to ambulation and discharge with the AXERA 2.
Conclusions
Use of the AXERA 2 device with micropuncture access did not infer increased bleeding risk than standard arterial access in this patient series. The considerable incidence of device use failures suggests a learning curve associated with its use.
PDF
