Thromboembolic Ischemic Stroke Research Articles

MRI-based microthrombi detection in stroke with polydopamine iron oxide

In acute ischemic stroke, even when successful recanalization is obtained, downstream microcirculation may still be obstructed by microvascular thrombosis, which is associated with compromised brain reperfusion and cognitive decline. Identifying these microthrombi through non-invasive methods remains challenging. We developed the PHySIOMIC (Polydopamine Hybridized Self-assembled Iron Oxide Mussel Inspired Clusters), a MRI-based contrast agent that unmasks these microthrombi. In a mouse model of thromboembolic ischemic stroke, our findings demonstrate that the PHySIOMIC generate a distinct hypointense signal on T2*-weighted MRI in the presence of microthrombi, that correlates with the lesion areas observed 24 hours post-stroke. Our microfluidic studies reveal the role of fibrinogen in the protein corona for the thrombosis targeting properties. Finally, we observe the biodegradation and biocompatibility of these particles. This work demonstrates that the PHySIOMIC particles offer an innovative and valuable tool for non-invasive in vivo diagnosis and monitoring of microthrombi, using MRI during ischemic stroke.

The Janus face of endogenous neuronal tPA: promoting self-protection and worsening the death of neighboring neurons

Recombinant tissue-type plasminogen activator (r-tPA/Actilyse) stands as the prevailing pharmacological solution for treating ischemic stroke patients, of whom because their endogenous circulating tPA alone is not sufficient to rescue reperfusion and to promote favorable outcome. Beyond the tPA contributed by circulating endothelial cells and hepatocytes, neurons also express tPA, sparking debates regarding its impact on neuronal fate ranging from pro-survival to neurotoxic properties. In order to investigate the role of neuronal tPA during brain injuries, we developed models leading to its conditional deletion in neurons, employing AAV9-pPlat-GFP and AAV9-pPlat-Cre-GFP along with tPA floxed mice. These models were subjected to N-methyl-D-aspartate (NMDA)-induced excitotoxicity or thromboembolic ischemic stroke in mice. Initially, we established that our AAV9 constructs selectively transduce neurons, bypassing other brain cell types. Subsequently, we demonstrated that tPA-expressing neurons exhibit greater resistance against NMDA-induced excitotoxicity compared to tPA negative neurons. The targeted removal of tPA in neurons heightened the susceptibility of these neurons to cell death and prevented a paracrine neurotoxic effect on tPA non-expressing neurons. Under ischemic conditions, the self-neuroprotective influence of tPA encompassed both excitatory (GFP+/Tbr1+) and inhibitory (GFP+/GABA+) neurons. Our data indicate that endogenous neuronal tPA is a protective or deleterious factor against neuronal death in an excitotoxic/ischemic context, depending on whether it acts as an autocrine or a paracrine mediator.

Design, rationale, and baseline characteristics of a randomized controlled trial evaluating a mobile relational agent to enhance atrial fibrillation self-care

Atrial fibrillation (AF) is a chronic cardiovascular disease that frequently causes disruptive symptoms, adverse outcomes, and poor health-related quality of life (HRQoL). We have developed a mobile health application for individuals with AF which provides a longitudinal, patient-centered program to improve self-care. The defining feature of the application is the use of a relational agent, which uses synthetic speech accompanied by animation to provide health education, empathic counseling, and monitoring. In the present manuscript we present the design, rationale, and baseline characteristics of participants enrolled in “A Mobile Relational Agent to Enhance Atrial Fibrillation Self-Care Trial,” a randomized trial testing the effectiveness the application for urban-dwelling individuals with AF being treated with oral anticoagulation for prevention of thromboembolic ischemic stroke. This is a single-center, parallel-arm randomized trial that assigned patients to the novel application (relational agent) versus a control intervention (WebMD). This ongoing RCT aims to determine the effect of the mobile health application on: (1) anticoagulation adherence; (2) patient-centered outcomes (quality of life and symptoms); and (3) health care utilization. The primary outcome, anticoagulation adherence, will be measured using the proportion of days covered (PDC). The study completed enrollment on April 1, 2022 (final enrollment n = 243 participants) with expected completion date of April 2023.(http://clinicaltrials.gov registration NCT04075994)

3D transcranial ultrasound localization microscopy for discrimination between ischemic and hemorrhagic stroke in early phase

Early diagnosis is a critical part of the emergency care of cerebral hemorrhages and ischemia. A rapid and accurate diagnosis of strokes reduces the delays to appropriate treatments and a better functional recovery. Currently, CTscan and MRI are the gold standards with constraints of accessibility, availability, and possibly some contraindications. The development of Ultrasound Localization Microscopy (ULM) has enabled new perspectives to conventional transcranial ultrasound imaging with increased sensitivity, penetration depth, and resolution. The possibility of volumetric imaging has increased the field-of-view and provided a more precise description of the microvascularisation. In this study, rats (n = 9) were subjected to thromboembolic ischemic stroke or intracerebral hemorrhages prior to volumetric ULM at the early phases after onsets. Although the volumetric ULM performed in the early phase of ischemic stroke revealed a large hypoperfused area in the cortical area of the occluded artery, it showed a more diffused hypoperfusion in the hemorrhagic model. Respective computations of a Microvascular Diffusion Index highlighted different patterns of perfusion loss during the first 24 h of these two strokes’ subtypes. Our study provides the first proof that this methodology should allow early discrimination between ischemic and hemorrhagic stroke with a potential toward diagnosis and monitoring in clinic.

Usefulness of maximum intensity projection images of non-enhanced CT for detection of hyperdense middle cerebral artery sign in acute thromboembolic ischemic stroke

PurposeTo compare the sensitivity of the hyperdense middle cerebral artery (MCA) sign between maximum intensity projection (MIP) and conventional averaged images in patients with acute focal neurological deficits with acute thromboembolic MCA occlusion (MCA occlusion group) and patients with acute focal neurological deficits without MCA occlusion (control group).Materials and methodsInitial computed tomography (CT) scans on admission were reconstructed with 5 mm thickness at every 3 mm interval for averaged and MIP images from 1 mm thickness non-contrast axial source images. Images were obtained from 30 cases each in the MCA occlusion and control groups. The CT values in the region of interests (ROIs) on the affected and unaffected sides of the MCA were compared. To compare CT values among subjects, the CT values were normalized by obtaining a ratio on the affected and unaffected sides, and the normalized CT values were analyzed using the receiver operating characteristic (ROC) curve.ResultsThe hyperdense MCA sign was visually detected on MIP images in 90% cases and on 5 mm averaged images in only 57% cases in the MCA occlusion group. Based on the ROC analysis of the normalized ratio on the affected and unaffected sides, area under the curve of MIP image and averaged image was 0.941 and 0.655, respectively. On MIP images, the optimal threshold of the ratio on the affected and unaffected sides was 1.152 (sensitivity: 90.0%, and specificity: 93.3%).ConclusionThe hyperdense MCA sign sensitivity on 5 mm MIP images was significantly higher than that on conventional 5 mm averaged CT images. This could be useful for the early initiation of proper therapy for patients with acute focal neurological deficits.

Fucoidan-functionalized polysaccharide submicroparticles loaded with alteplase for efficient targeted thrombolytic therapy

Intravenous administration of fibrinolytic drugs is the standard treatment of acute thrombotic diseases. However, current fibrinolytics exhibit limited clinical efficacy because of their short plasma half-lives and might trigger hemorrhagic transformations. Therefore, it is mandatory to develop innovative nanomedicine-based solutions for more efficient and safer thrombolysis with biocompatible and biodegradable thrombus-targeted nanocarrier. Herein, fucoidan-functionalized hydrogel polysaccharide submicroparticles with high biocompatibility are elaborated by the inverse miniemulsion/crosslinking method. They are loaded with the gold standard fibrinolytic – alteplase – to direct site-specific fibrinolysis due to nanomolar interactions between fucoidan and P-selectin overexpressed on activated platelets and endothelial cells in the thrombus area. The thrombus targeting properties of these particles are validated in a microfluidic assay containing recombinant P-selectin and activated platelets under arterial and venous blood shear rates as well as in vivo. The experiments on the murine model of acute thromboembolic ischemic stroke support this product's therapeutic efficacy, revealing a faster recanalization rate in the middle cerebral artery than with free alteplase, which reduces post-ischemic cerebral infarct lesions and blood-brain barrier permeability. Altogether, this proof-of-concept study demonstrates the potential of a biomaterial-based targeted nanomedicine for the precise treatment of acute thrombotic events, such as ischemic stroke.

Postoperative atrial fibrillation in paraesophageal hernia repair: can it be prevented?

Acute ischemic thromboembolic stroke is one of the most feared complications of atrial fibrillation (AF), and the risk increases with higher CHA2DS2-VASc scores. Postoperative atrial fibrillation (POAF) is common after noncardiac surgery, particularly after thoracic surgery, and can result in significant morbidity and mortality. We report the case of an 85-year-old female with a history of untreated hypertension (HTN) and no prior history of AF, who presented 5 days after an elective repair of a paraesophageal hernia with recurrence of a large type III paraesophageal hiatal hernia, AF, and subsequent acute thromboembolic ischemic stroke. Patient’s AF resolved shortly after treatment with calcium channel blocker. The risk of stroke is high in patients who develop AF and a period of 48 h after onset of AF is usually considered safe as the risk of stroke is low in this time period. However, this may not be the case during the perioperative period and preventive measures such as preoperative calcium channel blocker could be considered. Our case highlights that acute ischemic thromboembolic stroke might develop earlier tha 48 h after onset of POAF in patients undergoing paraesophageal hernia repair. Initiation of a calcium channel blocker should be considered during preoperative evaluation for patients undergoing paraesophageal hernia repairs, especially in those with untreated HTN.

Acute thromboembolic ischemic stroke in rural hospital, the role of early treatment in reducing brain damage

Introduction: Stroke has a high mortality and disability rate, and the main cause of physical disability in productive age and elderly. In developed countries stroke is the number one cause of admission of patients to hospital, with a mortality proportion of 20% within the first 28 days of treatmentCase Report: A 45-year-old man came to the neurology polyclinic of RSUD Aceh Besar on March 21st, 2021 with chief complaints of the general weakness of the left limb, complete numbness and heavy feeling in the left limb since 4 hours of before admission which is felt to be getting weaker from time to time, happened suddenly when the patient was working collecting stones. He complained of dizziness as well, and did not decrease while resting. After the attack, the patient remains conscious with no headache, no nausea and vomiting, no double images were seen. On Siriraj score showed result of -4. The patient was hospitalized with injection of Citicolin 1000 mg and then discharged 5 days later with significant improvement.Conclusion: Ischemic Stroke requires fast, precise and accurate handling to prevent and avoid disability and even death. One of the effective efforts is to organize health promotion and preventive programs starting from the First Level Health Facility (FKTP) on an ongoing basis to the community.

Immune Responses and Anti-inflammatory Strategies in a Clinically Relevant Model of Thromboembolic Ischemic Stroke with Reperfusion.

The poor clinical relevance of experimental models of stroke contributes to the translational failure between preclinical and clinical studies testing anti-inflammatory molecules for ischemic stroke. Here, we (i) describe the time course of inflammatory responses triggered by a thromboembolic model of ischemic stroke and (ii) we examine the efficacy of two clinically tested anti-inflammatory drugs: Minocycline or anti-CD49d antibodies (tested in stroke patients as Natalizumab) administered early (1h) or late (48h) after stroke onset. Radiological (lesion volume) and neurological (grip test) outcomes were evaluated at 24h and 5days after stroke. Immune cell responses peaked 48h after stroke onset. Myeloid cells (microglia/macrophages, dendritic cells, and neutrophils) were already increased 24h after stroke onset, peaked at 48h, and remained increased-although to a lesser extent-5days after stroke onset. CD8+ and CD4+ T-lymphocytes infiltrated the ipsilateral hemisphere later on (only from 48h). These responses occurred together with a progressive blood-brain barrier leakage at the lesion site, starting 24h after stroke onset. Lesion volume was maximal 24-48h after stroke onset. Minocycline reduced both lesion volume and neurological deficit only when administered early after stroke onset. The blockade of leukocyte infiltration by anti-CD49d had no impact on lesion volume or long-term neurological deficit, independently of the timing of treatment. Our data are in accordance with the results of previous clinical reports on the use of Minocycline and Natalizumab on ischemic stroke. We thus propose the use of this clinically relevant model of thromboembolic stroke with recanalization for future testing of anti-inflammatory strategies for stroke.

Thrombolytic Therapy for Acute Ischemic Stroke: Past and Future.

Thromboembolic ischemic stroke, which is mainly caused by hypertension, as well as plasma dyslipidemia, arterial fibrillation and diabetes, is a leading cause of death in the US and other countries. Numerous clinical trials for thrombolytic drugs, which aimed to pharmacologically dissolve thrombi, were conducted in the 1950s, when the first thrombolytic therapy was performed. In this study, we summarize the pathophysiologic features of ischemic stroke, and the history of thrombolytic therapy, and discuss the recent progress that has been made in the ongoing development of thrombolytic drugs. Thrombolytic therapy is sometimes accompanied by harmful hemorrhagic insults; accordingly, a window of time wherein therapy can safely be performed has been established for this approach. Several basic and clinical studies are ongoing to develop next-generation thrombolytic drugs to expand the time window.

P.097 Subarachnoid hemorrhage associated with a thromboembolic ischemic stroke- an unexpected observation

Atherosclerosis is a significant risk factor for ischemic stroke, and is a frequent cause for extra- and intra-cranial vessels stenosis. Here, we present an unusual case of ischemic stroke associated with intra-cranial vessel stenosis and subarachnoid hemorrhage (SAH) secondary to carotid artery atheroma. A 64-year old female known for hypertension and dyslipidemia presented with a three-day history of three transient episodes (< 30 minutes) of dysarthria and right hand weakness. An initial brain CT scan revealed left frontal SAH. She was admitted to our Stroke Unit for observation and management. CT-angiogram revealed 90% ICAs stenosis bilaterally with several short focal stenotic lesions, involving several left MCA branches. Brain MRI revealed acute infarcts in the left insula, external capsule and inferior frontal gyrus. The clinical picture was attributed to a thromboembolic left MCA ischemic stroke. She was managed with maximum medical therapy, and later underwent successful left carotid endarterectomy. The presence of SAH on our patient’s presenting CT scan lead to an initial radiological diagnosis of RCVS. However, subsequent imaging studies indicated that SAH had occurred in association with a thromboembolic ischemic stroke. Despite its rarity, this clinical association is important to recognize to avoid diagnostic confusion and guide appropriate management.

Aspirin for primary prevention of stroke in traumatic cerebrovascular injury: association with increased risk of transfusion.

Blunt traumatic extracranial carotid or vertebral artery injury (i.e., traumatic cerebrovascular injury [TCVI]) occurs in 1%-2% of all blunt trauma admissions, carries a 10% risk of thromboembolic ischemic stroke, and accounts for up to 9600 strokes annually in the US. Screening CT angiograms (CTAs) of patients with trauma has become ubiquitous in recent years, and patients with initially asymptomatic TCVI are commonly treated with antiplatelet agents to prevent stroke. Prophylaxis with antiplatelets is thought to be safer than anticoagulation, which carries a significant risk of hemorrhage in patients with trauma. However, the risk of hemorrhagic complications due to antiplatelets has not been assessed in this population. This is a retrospective cohort study of patients in whom a screening CTA was obtained after admission for blunt trauma at a Level 1 trauma center. Patients with CTAs indicating TCVI were treated routinely with 325 mg aspirin daily. The risk of transfusion > 24 hours after admission was compared according to CTA findings (CTA+ or CTA- for positive or negative findings, respectively) and aspirin treatment (ASA+ or ASA- for treatment or no treatment, respectively). The mean overall transfusion amount (number of units of packed red blood cells [PRBCs]) was 0.9 ± 2.1 for CTA+/ASA+ patients (n = 196) and 0.3 ± 1.60 for CTA-/ASA- patients (n = 2290) (p < 0.0001). In adjusted models, the overall relative risk (RR) of PRBC transfusion was 1.70 (1.32-2.20) for CTA+/ASA+ patients compared with CTA-/ASA- patients. Among age groups, participants whose ages were 50-69 years had the greatest significantly elevated RR (1.71, 95% CI 1.08-2.72) for CTA+/ASA+ patients compared with CTA-/ASA- patients. Treatment with aspirin for the prevention of stroke in patients with initially asymptomatic TCVI carries a significantly increased risk of PRBC transfusion. Future studies are needed to determine if this risk is offset by a reduced risk of ischemic stroke.

Abstract TMP90: Prevention of Stroke in Traumatic Cerebrovascular Injury With Aspirin Carries an Increased Risk of Transfusion

Introduction: Traumatic extracranial carotid or vertebral artery injury (TCVI) occurs in about 1% of all blunt trauma admissions, carries a 10% risk of thromboembolic ischemic stroke, and accounts for up to 2,400 strokes annually in the U.S. Screening CT angiography (CTA) of trauma patients is ubiquitous, and patients with initially asymptomatic TCVI are commonly treated with antiplatelet agents to prevent stroke. Although prophylaxis with these agents is thought to be safer than anticoagulation, which carries a sgnificant risk of hemorrhage in trauma patients, their risk of hemorrhagic complications is unknown. Methods: Single-center retrospective cohort study of patients with a screening CTA after admission for blunt trauma. Patients with CTA indicating TCVI were treated routinely with aspirin 325 mg daily. Risk of transfusion ≥1 unit of packed red blood cells (PRBC) &gt;24 hours after admission (excluding transfusions during injury-related blood loss) was assessed according to CTA findings (CTA+ or CTA-) and whether the patient was treated with aspirin (ASA+ or ASA-). Cox proportional hazards regression assuming equal time at risk was used to estimate risk ratios (RRs) and the relative excess risk due to interaction (RERI) for comparing risk of transfusion among the CTA/ASA groups. Results: The mean overall number of units of PRBC was 0.9±2.1 for CTA+/ASA+ patients (n=196) and 0.3±1.60 for CTA-/ASA- patients (n=2290) (&lt;0.0001). When adjusting for age, ISS, and INR ≥1.2 at admission, the overall RR of transfusion was 1.81 (95% CI 1.40-2.35) for CTA+/ASA+ patients compared to CTA-/ASA- patients. Among age groups, CTA+/ASA+ patients ages 50-69 years had the greatest RR (1.91 CI [1.21-3.03]) compared to CTA-/ASA- patients. Conclusion: Use of aspirin to prevent stroke in patients with TCVI carries a significantly increased risk of PRBC transfusion. Future studies are needed to determine if this increased risk of transfusion is offset by a reduced risk of ischemic stroke.

Acute Recanalization of Thrombo-Embolic Ischemic Stroke with pREset (ARTESp): the impact of occlusion time on clinical outcome of directly admitted and transferred patients

ObjectivesAcute Recanalization of Thrombo-Embolic Ischemic Stroke with pREset (ARTESp) is a prospective multicenter study assessing the efficacy and safety of the pREset stent retriever for the treatment of intracranial vessel...

Novel Diagnostic and Monitoring Tools in Stroke: an Individualized Patient-Centered Precision Medicine Approach.

Central to the pathogenesis of ischaemic stroke are the normally protective processes of platelet adhesion and activation. Experimental evidence has shown that the ligand-receptor interactions in ischaemic stroke represent a thrombo-inflammatory cascade, which presents research opportunities into new treatment. However, as anti-platelet drugs have the potential to cause severe side effects in ischaemic stroke patients (as well as other vascular disease patients), it is important to carefully monitor the risk of bleeding and risk of thrombus in patients receiving treatment. Because thrombo-embolic ischaemic stroke is a major health issue, we suggest that the answer to adequate treatment is based on an individualized patient-centered approach, inline with the latest NIH precision medicine approach. A combination of viscoelastic methodologies may be used in a personalized patient-centered regime, including thromboelastography (TEG®) and the lesser used scanning electron microscopy approach (SEM). Thromboelastography provides a dynamic measure of clot formation, strength, and lysis, whereas SEM is a visual structural tool to study patient fibrin structure in great detail. Therefore, we consider the evidence for TEG® and SEM as unique means to confirm stroke diagnosis, screen at-risk patients, and monitor treatment efficacy. Here we argue that the current approach to stroke treatment needs to be restructured and new innovative thought patterns need to be applied, as even approved therapies require close patient monitoring to determine efficacy, match treatment regimens to each patient's individual needs, and assess the risk of dangerous adverse effects. TEG® and SEM have the potential to be a useful tool and could potentially alter the clinical approach to managing ischaemic stroke. As envisaged in the NIH precision medicine approach, this will involve a number of role players and innovative new research ideas, with benefits that will ultimately only be realized in a few years. Therefore, with this ultimate goal in mind, we suggest that an individualized patient-orientated approach is now available and therefore already within our ability to use.

Partial MHC Constructs Treat Thromboembolic Ischemic Stroke Characterized by Early Immune Expansion.

Inflammation and thrombosis are tightly linked, with inflammation contributing to thromboembolism and to stroke outcome. Thromboembolism is a frequent cause of ischemic stroke; yet, the most used occlusion mouse models of experimental stroke do not effectively replicate thromboembolism. Our group recently described a novel thromboembolic mouse model of stroke that successfully occludes the middle cerebral artery with high reproducibility. In the current study, we characterize the peripheral and local immune outcomes as well as the ischemic response to immune therapy in a clinically relevant mouse model of thromboembolic stroke. Brain and spleen tissues were harvested 24 h after thromboembolic stroke and cells immunophenotyped by flow cytometry. We observed a significant increase in neutrophils and early activated T cells in the spleen and an increase in neutrophils and activated monocytes/microglia in the ischemic cortex after thromboembolic stroke. Moreover, as was shown previously for transient MCAO models, treatment of thromboembolic stroke with partial MHC constructs significantly reduced ischemic damage indicating an equivalent effect of this immune-based therapy in the thromboembolic model that better mimics the pathophysiology of human stroke.

PP-124 Detection of Paroxysmal Atrial Fibrillation after Iscemic Stroke and its Clinical Predictors

Atrial fibrillation (AF) whether paroxysmal or permanent is associated with increased risk of thromboembolic ischemic stroke and use of antithrombotic therapy reduce stroke risk This study was aimed to determine the frequency of newly detected AF using 24-hour Holter ECG after ischemic stroke and identify clinical predictors for AF.

Abstract T P187: How High Is Too High? An Analysis of the Upper Threshold for Serum FVIII in Ischemic Stroke

Background: Elevated factor VIII (FVIII) is an independent risk factor for thromboembolic events and acute ischemic stroke (AIS). Laboratory reference ranges categorize levels &gt;150% and &gt;200% activity as elevated and severely elevated, respectively. We sought to identify the upper limit of FVIII activity with the most clinical relevance for outcomes after AIS. Methods: From our stroke registry, patients admitted with AIS between 07/2008 to 10/2013 were included if FVIII levels were measured during admission. Logistic regression, was used to assess differences in baseline, in-hospital, and outcome variables in patients with FVIII elevation as compared to those with normal levels. The primary outcome was poor modified Rankin Scale (mRS) score on discharge, defined as mRS&gt;2. Serial dichotomized FVIII levels using a 5-point incremental analysis of levels were analyzed with respect to poor outcome. The threshold yielding the largest area under the curve (AUC) was determined. Results: Among 1,453 cases in our registry, inclusion criteria were met for 267 patients. In our sample, in a comparison of normal FVIII levels vs. elevation &gt;150%, and elevation &gt;200%, patients differed significantly according to race (p=0.0017), history of diabetes (p=0.0001), and history of congestive heart failure (p=0.0401). FVIII elevation threshold of 150% was the best predictor of poor mRS on discharge (OR 3.7, 95% CI 1.77-8.05, p=0.0006) with an AUC of 0.618. Conclusions: FVIII elevation greater than 150% is the most clinically useful threshold for the prediction of poor clinical outcomes in the setting of AIS based on data from our center.

Abstract W P154: Von Willebrand Factor Elevation Threshold for Poor Clinical Outcomes in Patients with Ischemic Stroke

Background: Elevation in von Willebrand factor (vWF) is an independent risk factor for thromboembolic events and acute ischemic stroke (AIS). Laboratory reference ranges categorize levels &gt;150% activity as abnormal. Our prior research demonstrated worse outcomes with severe (&gt;200%) elevation in vWF. We sought to determine the most clinically relevant threshold value for vWF with respect to patient outcome in AIS. Methods: From our stroke registry, patients admitted with AIS between 07/2008-10/2013 were included if vWF levels were measured during admission. Logistic regression was used to assess differences in baseline, in-hospital, and outcome variables in patients with vWF elevation as compared to those with normal levels. Optimal threshold levels were determined by assessing dichotomized vWF levels using a 5-point incremental analysis of levels with respect to outcome, and subsequent determination of the threshold yielding the largest area under the curve (AUC). The outcome was poor modified Rankin Scale (mRS) score on discharge, defined as mRS&gt;2. Results: Among 1,453 cases in our registry, inclusion criteria were met for 99 patients. Compared to patients with normal vWF, elevated vWF was associated with age, female gender, and diabetes. vWF elevation threshold of 200% was the best predictor of poor mRS on discharge (OR 2.88, 95% CI 1.32-6.29, p=0.0079) with an AUC of 0.629. Conclusions: Despite a laboratory cut-off of 150% as a normal value, elevation of vWF &gt;200% is the most clinically useful threshold for the prediction of poor clinical outcome in the setting of AIS based on data from our center.

Comparison of platelet ultrastructure and elastic properties in thrombo-embolic ischemic stroke and smoking using atomic force and scanning electron microscopy.

Thrombo-embolic ischemic stroke is a serious and debilitating disease, and it remains the second most common cause of death worldwide. Tobacco smoke exposure continues to be responsible for preventable deaths around the world, and is a major risk factor for stroke. Platelets play a fundamental role in clotting, and their pathophysiological functioning is present in smokers and stroke patients, resulting in a pro-thrombotic state. In the current manuscript, atomic force and scanning electron microscopy were used to compare the platelets of smokers, stroke patients and healthy individuals. Results showed that the elastic modulus of stroke platelets is decreased by up to 40%, whereas there is an elasticity decrease of up to 20% in smokers’ platelets. This indicates a biophysical alteration of the platelets. Ultrastructurally, both the stroke patients and smokers’ platelets are more activated than the healthy control group, with prominent cytoskeletal rearrangement involved; but to a more severe extent in the stroke group than in the smokers. Importantly, this is a confirmation of the extent of smoking as risk factor for stroke. We conclude by suggesting that the combined AFM and SEM analyses of platelets might give valuable information about the disease status of patients. Efficacy of treatment regimes on the integrity, cell shape, roughness and health status of platelets may be tracked, as this cell’s health status is crucial in the over-activated coagulation system of conditions like stroke.