Platelet Receptor Glycoprotein VI-Dimer Is Overexpressed in Patients with Atrial Fibrillation at High Risk of Ischemic Stroke.
Isuru InduruwaCarly KempsterPatrick ThomasHarriet McKinneyJean-Daniel MalcorArkadiusz BonnaJoana BatistaKenji SoejimaWillem OuwehandRichard W FarndaleKate DownesMasaaki MoroiStephanie M JungElizabeth A WarburtonPublished in: TH open : companion journal to thrombosis and haemostasis (2023)
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.
Keyphrases
- atrial fibrillation
- end stage renal disease
- poor prognosis
- oral anticoagulants
- left atrial
- catheter ablation
- ejection fraction
- clinical trial
- chronic kidney disease
- newly diagnosed
- direct oral anticoagulants
- heart failure
- peritoneal dialysis
- binding protein
- prognostic factors
- risk factors
- percutaneous coronary intervention
- healthcare
- emergency department
- long non coding rna
- acute coronary syndrome
- combination therapy
- open label
- phase ii