SLAP/SLAP2 prevent excessive platelet (hem)ITAM signaling in thrombosis and ischemic stroke in mice

In this study, we show that platelets expressed both SLAP isoforms and that overexpression of either protein in a heterologous cell line almost completely inhibited glycoprotein VI and C-type lectin-like receptor 2 signaling. In mice, single deficiency of SLAP or SLAP2 had only moderate effects on platelet function, whereas double deficiency of both adapters resulted in markedly increased signal transduction, integrin activation, granule release, aggregation, procoagulant activity, and thrombin generation in response to (hem)ITAM-coupled, but not G protein-coupled, receptor activation. In vivo, constitutive SLAP/SLAP2 knockout mice displayed accelerated occlusive arterial thrombus formation and a dramatically worsened outcome after focal cerebral ischemia. This was attributed to the absence of both adapter proteins in platelets, as demonstrated by adoptive transfer of Slap–/–/Slap2–/– platelets into wild-type mice. Our results establish SLAP and SLAP2 as critical inhibitors of platelet (hem)ITAM signaling in the setting of arterial thrombosis and ischemic stroke.
Source: Blood - Category: Hematology Authors: Tags: Free Research Articles, Platelets and Thrombopoiesis, Thrombosis and Hemostasis Source Type: research

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Publication date: Available online 14 February 2019Source: Biocybernetics and Biomedical EngineeringAuthor(s): G.B. Praveen, Anita Agrawal, Ponraj Sundaram, Sanjay SardesaiAbstractDetection of ischemic stroke lesions plays a vital role in the assessment of stroke treatments such as thrombolytic therapy and embolectomy. Manual detection and quantification of stroke lesions is a time-consuming and cumbersome process. In this paper, we present a novel automatic method to detect acute ischemic stroke lesions from Magnetic Resonance Image (MRI) volumes using textural and unsupervised learned features. The proposed method profic...
Source: Biocybernetics and Biomedical Engineering - Category: Biomedical Engineering Source Type: research
In conclusion, de-escalation of antiplatelet therapy is associated with nonsignificant differences in both ischemic events and major bleeding compared with standard potent antiplatelet therapy in patients undergoing percutaneous coronary intervention. The feasibility and even superiority of this strategy need to be elucidated by further randomized trials. PMID: 30759033 [PubMed - as supplied by publisher]
Source: Platelets - Category: Hematology Tags: Platelets Source Type: research
Abstract INTRODUCTION:  Cerebral micro-embolic signals (MES) predict risk of stroke in carotid stenosis patients. However, MES-negative 'recently symptomatic patients' also have a higher stroke risk than 'asymptomatic patients'. Differences in platelet activation status may contribute to this disparity in risk. METHODS:  This prospective, observational study assessed platelet biomarkers and their relationship with MES in asymptomatic versus symptomatic moderate (≥50-69%) or severe (≥70-99%) carotid stenosis patients. Full blood count parameters were measured and whole-blood flow cytometry was ...
Source: Thrombosis and Haemostasis - Category: Hematology Authors: Tags: Thromb Haemost Source Type: research
ConclusionsReversal of anticoagulation appears safe following LVAD-associated intracranial hemorrhage, though inadequate reversal was common. Resumption of warfarin±antiplatelet was associated with fewer fatal and non-fatal thrombotic events compared to antiplatelets alone, though more non-fatal hemorrhage events occurred.
Source: The Annals of Thoracic Surgery - Category: Cardiovascular & Thoracic Surgery Source Type: research
ConclusionsTreatment with tranexamic acid could reduce rebleeding and hematoma expansion in cerebral hemorrhage without an increase in single ischemic adverse events, but it could increase the risk of combined ischemic events; however, the lack of improvement in mortality and the poor functional outcomes limit the value of clinical application. These findings indicate that the most pertinent issue is the risk-to-benefit ratio with tranexamic acid treatment in cerebral hemorrhage.
Source: CNS Drugs - Category: Neurology Source Type: research
Interatrial block (IAB) is an ECG indicator of atrial fibrosis related to atrial remodeling and thrombus formation thus leading to embolic stroke and increasing mortality. We aimed to assess weather IAB predic...
Source: BMC Cardiovascular Disorders - Category: Cardiology Authors: Tags: Research article Source Type: research
CONCLUSIONS: Reversal of anticoagulation appears safe following LVAD-associated intracranial hemorrhage, though inadequate reversal was common. Resumption of warfarin±antiplatelet was associated with fewer fatal and non-fatal thrombotic events compared to antiplatelets alone, though more non-fatal hemorrhage events occurred. PMID: 30763560 [PubMed - as supplied by publisher]
Source: The Annals of Thoracic Surgery - Category: Cardiovascular & Thoracic Surgery Authors: Tags: Ann Thorac Surg Source Type: research
This study assessed TTR using the Rosendaal Method prior to suspected or confirmed pump thrombosis or ischemic stroke. Each patient served as their own control. Characteristics and TTR in 1, 2, and 3 months prior to thrombus (thrombus period) were compared to a thrombus-free period during 6 months to 3 months prior to thrombus (control period). There were 30 thrombus events observed in 25 patients for a rate of 0.06 events per LVAD day. Average TTR (target INR  = 2–3) over 3 months for patients combined in both the thrombus and control time period was 53.4%. TTR (target INR = 2–3) wa...
Source: Journal of Thrombosis and Thrombolysis - Category: Hematology Source Type: research
We present the case of a 4-year-old boy with complex congenital heart disease, admitted 30 min after sudden onset of an aphasia and right hemiplegia, scoring 14 on the Pediatric National Institutes of Health Stroke Scale (PedNIHSS). Non-contrast brain computed tomography (CT) showed no evidence of acute ischemia. CT angiogram demonstrated a thrombus in the M1 segment of the left middle cerebral artery. Intravenous recombinant tissue plasminogen activator (rTPA) was infused 3.5 h after onset of symptoms. An improvement was observed in the hour after rTPA, with a PedNIHSS score of 7. Digital subtraction angiography was perfo...
Source: Case Reports in Neurology - Category: Neurology Source Type: research
Publication date: Available online 7 February 2019Source: The LancetAuthor(s): Craig S Anderson, Yining Huang, Richard I Lindley, Xiaoying Chen, Hisatomi Arima, Guofang Chen, Qiang Li, Laurent Billot, Candice Delcourt, Philip M Bath, Joseph P Broderick, Andrew M Demchuk, Geoffrey A Donnan, Alice C Durham, Pablo M Lavados, Tsong-Hai Lee, Christopher Levi, Sheila O Martins, Veronica V Olavarria, Jeyaraj D PandianSummaryBackgroundSystolic blood pressure of more than 185 mm Hg is a contraindication to thrombolytic treatment with intravenous alteplase in patients with acute ischaemic stroke, but the target systolic blood pressu...
Source: The Lancet - Category: General Medicine Source Type: research
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