Mechanical behavior of in vitro blood clots and the implications for acute ischemic stroke treatment

2019 ◽  
Vol 12 (9) ◽  
pp. 853-857 ◽  
Author(s):  
Sarah Johnson ◽  
Juyu Chueh ◽  
Matthew J Gounis ◽  
Ray McCarthy ◽  
J Patrick McGarry ◽  
...  

BackgroundClot mechanical properties are influenced by composition and the arrangement of components within the clot. This work investigates the effects of platelet-driven contraction on blood clot microstructure and mechanical behavior, and provides insight into some implications for mechanical thrombectomy.MethodsPlatelet-contracted clot analogues (PCCs) and non-contracted clot analogues (NCCs) were prepared from blood mixtures of various hematocrits (%H), that is, the volume percentage of red blood cells (RBCs) in the mixture. Mechanical testing was performed to compare the behavior of the analogues with previously tested human thromboemboli. Scanning electron microscopy and histology investigated the clot microstructure and composition. The association between clot properties and their behavior during mechanical behavior was also investigated.ResultsOverall, PCCs were found to be stiffer than NCCs, across all hematocrits. PCCs with a low %H resisted complete ingestion via contact aspiration alone or complete retrieval with stent-retrievers. PCCs with a higher %H and all NCCs were fully retrievable, although the likelihood of fragmentation was increased in clots with a greater %H. Histologically, there was little difference in the RBC and fibrin content between PCCs and NCCs with the same %H. However, the microstructure of the two groups differed significantly.ConclusionA selection of repeatable clot analogues with a range of mechanical properties have been developed for in vitro modeling of acute ischemic stroke. Platelet contraction significantly affects clot volume and microstructure, and in turn clot stiffness. The significant difference in mechanical properties and microstructure, but without an appreciable difference in histology, implies that histological studies of explanted human clots alone may not prove to be predictive of the mechanical behavior of the clots in thrombectomy.

Stroke ◽  
2021 ◽  
Vol 52 (Suppl_1) ◽  
Author(s):  
RAJAN R GADHIA ◽  
Farhaan S Vahidy ◽  
Tariq Nisar ◽  
Destiny Hooper ◽  
David Chiu ◽  
...  

Objective: Most acute stroke treatment trials exclude patients above the age of 80. Given the clear benefit of revascularization with intravenous tissue plasminogen activator (IV tPA) and mechanical thrombectomy (MT), we sought to assess functional outcomes in patients treated above the age of 80. Methods: We conducted a review of all patients admitted to Houston Methodist Hospital between January 2019 and August 2020 with an acute ischemic stroke (AIS) presentation[MOU1] for whom premorbid, discharge, and 90 day modified Rankin Scale scores were available. Patients were categorized by acute stroke treatment (IV tPA, MT, both or none[MOU2] ). mRS values were assessed during admission prior to discharge and at 90 days post stroke event. A delta mRS (Discharge vs. 90-day [MOU3] ) was defined and grouped as no change, improved, or worsened to assess overall functional disability in regards to the index stroke presentation. Results: A total of 865 patients with AIS presentation were included, of whom 651 (75.3%) were <80 years and 214 (24.7%) were > 80 years of age at presentation. A total of 208 patients received IV tPA, 176 underwent revascularization with MT only, 71 had both treatments, and 552 had no acute intervention. In patients >80 yrs who had no acute stroke intervention. mRS improvement was noted in 71.4% compared to 54.1% observed in those patients <80 years. Among patients who received IV tPA, 81.5% of > 80 years improved vs. 61.6% in the younger cohort. A similar trend was noted in the MT and combined treatment groups (76.2% vs. 71.2% and 78.6% vs. 79.3%, respectively). Conclusion: Based on our cohort of acute stroke patients, there was no significant difference in outcomes (as measured by delta mRS) for octogenarians and nonagenarians when compared to younger patients. There was a trend towards improvement in the elderly patients. Chronological age by itself may be an insufficient predictor of functional outcome among stroke patients and age cutoffs for enrollment of patients in acute stroke trials may need additional considerations.


Author(s):  
Jawid Madjidyar ◽  
Lars Nerkada ◽  
Naomi Larsen ◽  
Fritz Wodarg ◽  
Johannes Hensler ◽  
...  

Purpose A direct aspiration first pass technique (ADAPT) is an effective thrombectomy option in patients with acute ischemic stroke. Balloon guide catheters (BGC) seem to improve the efficacy of stent retrievers and ADAPT. The last generation 6F aspiration catheters require 9F BGCs, which are rigid devices that are challenging to position in a tortuous anatomy. In this experimental study the efficacy of 6F ADAPT alone and 5F ADAPT combined with 8F BGC was evaluated. Materials and Methods Either a fibrin rich (white) clot or an RBC rich (red) clot was placed in the M1 segment of a transparent silicon phantom. Physiological hemodynamic conditions were maintained. The clots were retrieved by 6F aspiration catheter via 8F long sheath or 5F aspiration catheter via a flexible 8F BGC. Thrombectomy was performed under direct visual control. The primary endpoints were the number of passes and the number of distal emboli. Results Ten experiments were made with each clot model and thrombectomy technique (n = 40). Full recanalization could be achieved in every experiment. First pass mTICI 3 could be achieved by 6F ADAPT in 80 % of red clots and 90 % of white clots. Distal emboli were caused in 10 % and 20 %, respectively. When using 5F ADAPT combined with BGC, a first pass mTICI 3 rate of 90 % in red clots and 100 % in white clots could be achieved. A 10 % rate of distal emboli occurred in both groups. In almost all experiments (both techniques), the thrombi clogged the aspiration catheter. No statistically significant differences could be found between the techniques and clot models. Conclusion 6F ADAPT without BGC was as effective as 5F ADAPT combined with a flexible 8F BGC, with both techniques showing high first-pass recanalization rates and low distal emboli rates. Especially in the case of a tortuous anatomy, these setups should be considered as alternatives to a rigid 9F BGC. The thrombus compositions seemed to be irrelevant in this setting. Key Points:  Citation Format


2017 ◽  
Vol 10 (4) ◽  
pp. 345-350 ◽  
Author(s):  
Tomas Dobrocky ◽  
Eike Piechowiak ◽  
Alessandro Cianfoni ◽  
Felix Zibold ◽  
Luca Roccatagliata ◽  
...  

Background and purposeThrombus composition has been postulated to affect the success of endovascular therapy. Calcified clots are composed of large amounts of calcium phosphate which influences their mechanical properties and may serve as a model for testing this hypothesis. The aim of this study was to evaluate the recanalization and complication rates of calcified thromboemboli in patients with acute ischemic stroke who underwent thrombectomy.Material and methodsA retrospective analysis was performed of all calcified intracranial thromboemboli in patients suffering an acute ischemic stroke, referred for endovascular therapy at two centers between January 2013 and July 2016.ResultsEight patients with a calcified intracranial clot underwent stent retriever thrombectomy (five women; mean age 80 years). Mean clot attenuation was 305 HU (range 150–640 HU). Successful reperfusion defined, as Thrombolysis in Cerebral Infarction grade 2b–3 was achieved in only one patient (12.5%). Two periprocedural adverse events occurred: one peripheral vessel perforation which was coiled and one inadvertent stent retriever detachment due to fracture of the stent retriever wire.ConclusionStent retriever thrombectomy of calcified thromboemboli seems less effective than with other types of clots. Different mechanical properties of calcified clots may render them stiffer and less accessible for stent retrievers. When faced with a calcified intracranial thromboembolus in clinical practice, a more contained approach may be warranted in view of low recanalization rates, and the potential for periprocedural adverse events.


Blood ◽  
2016 ◽  
Vol 128 (22) ◽  
pp. 4998-4998 ◽  
Author(s):  
Valerie Tutwiler ◽  
Alina Peshkova ◽  
Dina Khasanova ◽  
John W. Weisel ◽  
Rustem I. Litvinov

Abstract Obstructive thrombi or thrombotic emboli of cerebral arteries are the pathogenic basis of ischemic stroke, which is a leading cause of death and disability worldwide. Blood clots undergo volume shrinkage due to the contractile forces that are generated by platelets and propagated through the clot volume due to platelet-fibrin interactions and elasticity of the fibrin network. This process is designed clot contraction (retraction) which remains one of the least studied steps of blood clotting. Importantly, this phenomenon has been shown to occur not only in vitro but also in in vivo thrombi. Clot contraction has been shown to be important in the volume reduction of otherwise obstructive thrombi and has the potential to reduce occlusion and restore blood flow past emboli or thrombi. Despite the potential medical significance of clot contraction, it has not been examined systemically in a clinical setting. This aim of this work was to examine the potential pathogenic role of clot contraction in ischemic stroke. Here we employed a novel automated method to quantify the time of initiation, extent and rate of clot contraction in vitro to compare clot contraction in the blood of healthy subjects with patients suffering a recent ischemic stroke (<6 hours from the onset of symptoms) who had not yet received any treatment with anticoagulants, antiplatelet drugs or thrombolytics.. Parameters of clot contraction were correlated with the severity and etiological types of stroke as well as with hematological, coagulation, and biochemical tests to examine the clinical significance of clot contraction. The main finding of this work is that clot contraction in blood from patients with acute ischemic stroke is reduced on average by ~60% (p<0.0001) when compared to that of healthy subjects. The reduction in clot contraction is correlated with a lower platelet count and platelet dysfunction, higher fibrinogen level, higher hematocrit, leukocytosis as well as other changes in the blood composition of patients with ischemic stroke that may alter the properties of the blood clot. We propose that these changes in the composition of the blood contribute to the impaired mechanism of clot contraction, which may exaggerate vessel occlusion and brain infarct. While stroke severity is determined mainly by the diameter and location of the obstructed cerebral artery, the ability of the thrombi to contract more or less may augment or ease the course of brain damage. Clinical correlations with respect to severity and stroke etiology indicate that reduced clot contraction has the potential to be a pathogenic factor in ischemic stroke. Paradoxically, the extent of clot contraction marginally improved in patients with a more severe stroke (NIHSS>15 vs. NIHSS<15, p<0.01), while it was still significantly reduced compared to healthy subjects. This finding can be presumably explained by the fact that in severe brain damage a massive amount of tissue factor is released into the systemic circulation, which can induce the activation of blood coagulation. We propose that this release of tissue factor results in a secondary wave of thrombin generation that causes patients with more severe stroke to have hyperactivity of platelets. In combination with a higher platelet count (p<0.01) this can enhance contraction of obstructive clots or thrombi, which may be a compensatory mechanism resulting in the recanalization of an otherwise occluded blood vessel. In support of this hypothetical scenario, it was also found that patients with atherothrombotic strokes have an increased extent of clot contraction compared to patients with cardioembolic stroke (p<0.05), and atherothrombotic patients are reported to have increased tissue factor as a consequence of atherosclerotic lesions. In summary, the clinical pathophysiological importance of clot contraction in a thrombotic state has been examined for the first time and the modulation of the ability of clots or thrombi to shrink in volume may be a novel and unappreciated mechanism that aggravates or alleviates the course and outcomes of thrombosis, such as ischemic stroke. The clinical importance of clot or thrombus remodeling in vivo as well as the diagnostic and prognostic value of this blood test for clot contraction needs further exploration. Disclosures Weisel: Bayer: Research Funding.


2018 ◽  
Vol 7 (6) ◽  
pp. 327-333 ◽  
Author(s):  
Mohamed S. Teleb

Background: Treatment of large vessel occlusion acute ischemic stroke with mechanical thrombectomy has become the standard of care after recent clinical trials. However, the degree of recanalization with stent retrievers remains very important in overall outcomes. We sought to review the utility of a new balloon guide catheter (BGC) in improving the degree of recanalization in conjunction with mechanical thrombectomy. Methods: The medical records of a prospectively collected endovascular ischemic stroke database were reviewed. All consecutive strokes when a FlowGate BGC was used with a thrombectomy stent retriever were identified. Use of a FlowGate BGC, number of passes, final Thrombolysis in Cerebral Infarction (TICI) score, trackability, and use of adjunct devices were all collected and analyzed. Results: Use of a FlowGate BGC resulted in 64% (33/52) first-pass effect (FPE) of TICI 2b/3, and specifically 46% (24/52) TICI 3 FPE (true FPE). A total of 52/62 (84%) of thrombectomy cases were treated with BGCs. In the remaining 10, the BGC was not inflated or used due to the clot not being visualized or the lesions being distal and BGC use thus not deemed appropriate. Adjunct use of an aspiration catheter was seen in 12% (6/52) of cases. The overall success with FlowGate BGCs with one or more passes of TICI 2b/3 was 94% (49/52). Trackability was achieved in 92% (57/62) of cases. Conclusions: Use of the FlowGate BGC as an adjunct to mechanical thrombectomy was associated with good FPE and an overall recanalization of TICI 2b/3 of 94%.


2018 ◽  
Vol 24 (2) ◽  
pp. 20-29
Author(s):  
А.М. Netliukh ◽  
V.М. Shevaga ◽  
A.V. Payenok ◽  
В.M. Salo ◽  
О.Ya. Kobyletskyi

Objective — to estimate safety and effectiveness of intra-arterial treatment for acute ischemic stroke in the interventional radiology department of multiprofile hospital. Materials and methods. Urgent endovascular treatment was applied at 15 patients with acute ischemic stroke in carotid circulation during 2015–2017. Mechanical intra-arterial therapy with thrombectomy by stent-retrievers and thromboaspiration was used at accordingly six and two recent cases (during 2017); in 7 cases intra-arterial thrombolysis was the treatment option (2015–2016). Results. The article consist brief review of literature about acute ischemic stroke treatment and discussion concerning results of treatment of selected patients. Mechanical thrombectomy or thromboaspiration were effective in 75.0 % of cases with good recanalization rate opposite to 42.9 % at 7 patients treated by either intra-arterial or bridging thrombolysis with rt-PA. Unexpected technical failures of mechanical thrombectomy regarding recent clinical guidelines for ischemic stroke management following are discussed on example of 2 clinical cases. Conclusions. Endovascular treatment of ischemic stroke has a high safety and well-known efficacy. It became evident at our patients that following current management guidelines for thrombectomy with stent-retrievers or thromboaspiration after thrombotic occlusions of extracranial and proximal segments of intracranial arteries allowed attaining in 2017 reperfusion rate 2b/3 Modified Treatment in Cerebral Ischaemia Scale in majority of cases. Intra-arterial thrombolysis contributed to the reperfusion rate 2b/3 on the Modified Treatment in Cerebral Ischaemia scale just in 42.9 % of cases, which indicates its lower effectiveness.


2021 ◽  
Vol 9 ◽  
Author(s):  
Yuxuan Lu ◽  
Weiping Sun ◽  
Zhiyuan Shen ◽  
Wei Sun ◽  
Ran Liu ◽  
...  

Background and Purpose: Studies on the regional differences in hospital costs of acute ischemic stroke (AIS) are scarce in China. We aimed to explore the regional differences in hospital costs and identify the determinants of hospital costs in each region.Methods: Data were collected from the Chinese Acute Ischemic Stroke Treatment Outcome Registry (CASTOR), a multicenter prospective study on patients diagnosed with AIS and hospitalized from 2015 to 2017. Univariate and multivariate analyses were undertaken to identify the determinants of hospital costs of AIS.Results: A total of 8,547 patients were included in the study, of whom 3,700 were from the eastern area, 2,534 were from the northeastern area, 1,819 were from the central area, and 494 were from the western area. The median hospital costs presented a significant difference among each region, which were 2175.9, 2175.1, 2477.7, and 2282.4 dollars in each area, respectively. Each region showed a similar hospital cost proportion size order of cost components, which was Western medicine costs, other costs, diagnostic costs, and traditional medicine costs, in descending order. Male sex, diabetes mellitus, severe stroke symptoms, longer length of stay, admission to the intensive care unit, in-hospital complications of hemorrhage, and thrombectomy were independently associated with hospital costs in most regions.Conclusion: Hospital costs in different regions showed a similar proportion size order of components in China. Each region had different determinants of hospital costs, which reflected its current medical conditions and provided potential determinants for increasing medical efficiency according to each region's situation.


Stroke ◽  
2017 ◽  
Vol 48 (suppl_1) ◽  
Author(s):  
Ameer E Hassan ◽  
Christina Sanchez ◽  
Asad Ahrar ◽  
Saqib A Chaudhry ◽  
Adnan I Qureshi

Background: There is controversy regarding the optimal size of stent retriever for achieving timely recanalization in acute ischemic stroke patients. Objective: To determine the relationship between stent retriever diameter and procedure time, and rates of recanalization, and functional independence among acute ischemic stroke patients undergoing mechanical thrombectomy. Methods: We analyzed data from consecutive acute ischemic stroke patients treated with mechanical thrombectomy derived from a prospective database. Baseline demographic and clinical characteristics, NIHSS score on admission and discharge, intracranial hemorrhage occurrence, and mRS at discharge were analyzed. Thrombolysis In Cerebral Infarction (TICI) scale was used to grade pre and post procedure angiographic recanalization. Procedural time was defined by the time interval between microcatheter placement and recanalization. We compared the rates of thrombectomy attempts, complete recanalization (TICI grade of 3), and functional independence (defined by mRS 0-2) between patients treated with 6 mm and 3-4 mm diameter stent retrievers. Results: A total of 230 acute ischemic stroke patients (mean age 71.8 ±12.5; 46.6% women) were treated with stent retrievers. Thrombectomy was performed with a 6mm diameter stent retriever in 107 patients and 3 or 4 mm diameter stent retriever in 123 patients. There were no statistically significant differences in demographics or baseline characteristics, or admission NIHSS score between the two groups. There was a trend towards a fewer number of thrombectomy attempts required with a 6mm diameter stent retriever (p=0.06). There was a higher rate of complete recanalization in patients treated with 6mm diameter stent retriever compared with 3 or 4 mm diameter stent retriever (72% vs 57.7% p=0.02). There was no statistically significant difference in rates of functional independence between the two groups (24.3% vs 25.2% p=0.84) at discharge. Conclusion: Among acute ischemic stroke patients undergoing mechanical thrombectomy, use of a 6 mm diameter stent retriever was associated with a higher rate of complete recanalization and a lower number of thrombectomy attempts compared with 3-4 mm diameter stent retrievers.


Stroke ◽  
2020 ◽  
Vol 51 (Suppl_1) ◽  
Author(s):  
Seán Fitzgerald ◽  
Daying Dai ◽  
Andrew S Douglas ◽  
Oana M Mereuta ◽  
Thomas Caracena ◽  
...  

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.


Author(s):  
S.T. Fitzgerald ◽  
Y. Liu ◽  
D. Dai ◽  
O.M. Mereuta ◽  
M. Abbasi ◽  
...  

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