The increasing burden of atrial fibrillation in acute medical admissions, an opportunity to optimise stroke prevention

Background Atrial fibrillation is a major risk factor for ischaemic stroke. We investigated whether active screening for atrial fibrillation in secondary care, followed by careful evaluation of risk factors and communication to general practitioners from stroke specialists, could increase appropriate anticoagulation prescription. Methods Between 1/9/14 and 28/2/15 all acute medical admissions were screened for atrial fibrillation at Cambridge University Hospital. Individualised letters were sent to the general practitioners of patients who it was felt would benefit from anticoagulation. Results In total, 847 patients with atrial fibrillation (15% prevalence, 52% female, median age 81.9 years, median CHA2DS2–VASc 4.4) were identified; 671 (79.2%) had known atrial fibrillation, and 176 (20.8%) were diagnosed on admission. After screening and identifying ‘at risk’ patients, 112 individualised letters were sent to GPs. A 91% response rate was achieved, resulting in an additional 43 individuals being appropriately anticoagulated. Conclusions Atrial fibrillation prevalence is significantly increasing among acute hospital admissions; these patients have high risk of cardioembolic stroke. Careful screening and identification in secondary care can lead to improved rates of anticoagulation

Platelet collagen receptor Glycoprotein VI-dimer recognizes fibrinogen and fibrin through their D-domains, contributing to platelet adhesion and activation during thrombus formation.

UNLABELLED: Essentials Glycoprotein VI (GPVI) binds collagen, starting thrombogenesis, and fibrin, stabilizing thrombi. GPVI-dimers, not monomers, recognize immobilized fibrinogen and fibrin through their D-domains. Collagen, D-fragment and D-dimer may share a common or proximate binding site(s) on GPVI-dimer. GPVI-dimer-fibrin interaction supports spreading, activation and adhesion involving αIIbβ3. SUMMARY: Background Platelet collagen receptor Glycoprotein VI (GPVI) binds collagen, initiating thrombogenesis, and stabilizes thrombi by binding fibrin. Objectives To determine if GPVI-dimer, GPVI-monomer, or both bind to fibrinogen substrates, and which region common to these substrates contains the interaction site. Methods Recombinant GPVI monomeric extracellular domain (GPVIex ) or dimeric Fc-fusion protein (GPVI-Fc2 ) binding to immobilized fibrinogen derivatives was measured by ELISA, including competition assays involving collagenous substrates and fibrinogen derivatives. Flow adhesion was performed with normal or Glanzmann thrombasthenic (GT) platelets over immobilized fibrinogen, with or without anti-GPVI-dimer or anti-αIIbβ3. Results Under static conditions, GPVIex did not bind to any fibrinogen substrate. GPVI-Fc2 exhibited specific, saturable binding to both D-fragment and D-dimer, which was inhibited by mFab-F (anti-GPVI-dimer), but showed low binding to fibrinogen and fibrin under our conditions. GPVI-Fc2 binding to D-fragment or D-dimer was abrogated by collagen type III, Horm collagen or CRP-XL (crosslinked collagen-related peptide), suggesting proximity between the D-domain and collagen binding sites on GPVI-dimer. Under low shear, adhesion of normal platelets to D-fragment, D-dimer, fibrinogen and fibrin was inhibited by mFab-F (inhibitor of GPVI-dimer) and abolished by Eptifibatide (inhibitor of αIIbβ3), suggesting that both receptors contribute to thrombus formation on these substrates, but αIIbβ3 makes a greater contribution. Notably, thrombasthenic platelets showed limited adhesion to fibrinogen substrates under flow, which was further reduced by mFab-F, supporting some independent GPVI-dimer involvement in this interaction. Conclusion Only dimeric GPVI interacts with fibrinogen D-domain, at a site proximate to its collagen binding site, to support platelet adhesion/activation/aggregate formation on immobilized fibrinogen and polymerized fibrin

The increasing burden of atrial fibrillation in acute medical admissions, an opportunity to optimise stroke prevention.

Background Atrial fibrillation is a major risk factor for ischaemic stroke. We investigated whether active screening for atrial fibrillation in secondary care, followed by careful evaluation of risk factors and communication to general practitioners from stroke specialists, could increase appropriate anticoagulation prescription. Methods Between 1/9/14 and 28/2/15 all acute medical admissions were screened for atrial fibrillation at Cambridge University Hospital. Individualised letters were sent to the general practitioners of patients who it was felt would benefit from anticoagulation. Results In total, 847 patients with atrial fibrillation (15% prevalence, 52% female, median age 81.9 years, median CHA2DS2-VASc 4.4) were identified; 671 (79.2%) had known atrial fibrillation, and 176 (20.8%) were diagnosed on admission. After screening and identifying 'at risk' patients, 112 individualised letters were sent to GPs. A 91% response rate was achieved, resulting in an additional 43 individuals being appropriately anticoagulated. Conclusions Atrial fibrillation prevalence is significantly increasing among acute hospital admissions; these patients have high risk of cardioembolic stroke. Careful screening and identification in secondary care can lead to improved rates of anticoagulation