Anti-GPVI Fab Reveals Distinct Roles for GPVI Signaling in the First Platelet Layer and Subsequent Layers During Microfluidic Clotting on Collagen with or Without Tissue Factor

Zhang, Yiyuan; Trigani, Kevin T.; Shankar, Kaushik Nagaraj; Crossen, Jennifer Theresa; Sinno, Talid; Diamond, Scott L.

doi:10.2139/ssrn.4068772

Cited by 1 publication

(1 citation statement)

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“…Other studies employing Fab blockade of GPVI have demonstrated similar results, highlighting the importance of GPVI–fibrin interactions in maintaining thrombus integrity during the early stages of thrombosis. 28…”

Section: Discussionmentioning

confidence: 99%

Platelet Receptor Glycoprotein VI-Dimer Is Overexpressed in Patients with Atrial Fibrillation at High Risk of Ischemic Stroke

Induruwa,

Kempster,

Thomas

et al. 2023

TH Open

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Introduction Atrial fibrillation (AF) increases the risk of ischemic stroke (IS). We hypothesized that the functional form of platelet receptor glycoprotein (GP) VI, GPVI-dimer, which binds to collagen and fibrin causing platelet activation, is overexpressed in patients with AF who have not had a stroke. Methods A total of 75 inpatients with AF were recruited. None were admitted with or had previously had thrombotic events, including IS or myocardial infarction. Platelet surface expression of total GPVI, GPVI-dimer, and the platelet activation marker P-selectin were quantitated by whole blood flow cytometry. Serum biomarkers were collected in AF patients. Results were compared against patients contemporaneously admitted to hospital with similar age and vascular risk-factor profiles without AF (noAF, n = 30). Results Patients with AF have similar total GPVI surface expression (p = 0.58) and P-selectin exposure (p = 0.73) on their platelets compared with noAF patients but demonstrate significantly higher GPVI-dimer expression (p = 0.02). Patients with paroxysmal AF express similar GPVI-dimer levels compared with permanent AF and GPVI-dimer levels were not different between anticoagulated groups. Serum N-terminal pro b-type natriuretic peptide (p < 0.0001) and high sensitivity C-reactive protein (p < 0.0001) were significantly correlated with GPVI-dimer expression in AF platelets. AF was the only vascular risk factor that was independently associated with higher GPVI-dimer expression in the whole population (p = 0.02). Conclusion GPVI inhibition is being explored in clinical trials as a novel target for IS treatment. As GPVI-dimer is elevated in AF patients' platelets, the exploration of targeted GPVI-dimer inhibition for stroke prevention in patients at high risk of IS due to AF is supported.

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Section: Discussionmentioning

confidence: 99%