title: The changes in clot microstructure in patients with ischaemic stroke and the effects of therapeutic intervention: a prospective observational study.
abstract: BACKGROUND
  Stroke is the second largest cause of death worldwide. Hypercoagulability is a key feature in ischaemic stroke due to the development of an abnormally dense clot structure but techniques assessing the mechanics and quality of clot microstructure have limited clinical use. We have previously validated a new haemorheological technique using three parameters to reflect clot microstructure (Fractal Dimension (d f )) ex-vivo, real-time clot formation time (T GP ) and blood clot strength (elasticity at the gel point (G'GP)). We aimed to evaluate these novel clotting biomarkers in ischaemic stroke and changes of clot structure following therapeutic intervention.
  
  
  METHODS
  In a prospective cohort study clot microstructure was compared in ischaemic stroke patients and a control group of healthy volunteers. Further assessment took place at 2-4 hours and at 24 hours after therapeutic intervention in the stroke group to assess the effects of thrombolysis and anti-platelet therapy.
  
  
  RESULTS
  75 patients (mean age 72.8 years [SD 13.1]; 47 male, 28 female) with ischaemic stroke were recruited. Of the 75 patients, 32 were thrombolysed with t-PA and 43 were loaded with 300 mg aspirin. The following parameters were significantly different between patients with stroke and the 74 healthy subjects: d f (1.760 ± .053 versus 1.735 ± 0.048, p = 0.003), TGP (208 ± 67 versus 231 ± 75, p = 0.05), G'GP (0.056 ± 0.017 versus 0.045 ± 0.014, p < 0.0001) and fibrinogen (3.7 ± 0.8 versus 3.2 ± 0.5, p < 0.00001). There was a significant decrease in d f (p = 0.02), G'GP (p = 0.01) and fibrinogen (p = 0.01) following the administration of aspirin and for d f (p = 0.003) and fibrinogen (p < 0.001) following thrombolysis as compared to baseline values.
  
  
  CONCLUSIONS
  Patients with ischaemic stroke have denser and stronger clot structure as detected by d f and G'GP. The effect of thrombolysis on clot microstructure (d f ) was more prominent than antiplatelet therapy. Further work is needed to assess the clinical and therapeutic implications of these novel biomarkers.
authors.affiliation: School of Medicine, Swansea University, Swansea, UK. S.N.Stanford@swansea.ac.uk.|NISCHR Haemostasis Biomedical Research Unit, Morriston Hospital, ABMU Health Board, Swansea, SA6 6NL, UK. S.N.Stanford@swansea.ac.uk.
authors.forename: Sophia N
authors.initials: SN
authors.lastname: Stanford
authors.affiliation: School of Medicine, Swansea University, Swansea, UK. drsabraa@yahoo.com.|NISCHR Haemostasis Biomedical Research Unit, Morriston Hospital, ABMU Health Board, Swansea, SA6 6NL, UK. drsabraa@yahoo.com.|The Emergency Department, Morriston Hospital, ABMU Health Board, Swansea, UK. drsabraa@yahoo.com.
authors.forename: Ahmed
authors.initials: A
authors.lastname: Sabra
authors.affiliation: School of Medicine, Swansea University, Swansea, UK. L.A.DSilva@swansea.ac.uk.|NISCHR Haemostasis Biomedical Research Unit, Morriston Hospital, ABMU Health Board, Swansea, SA6 6NL, UK. L.A.DSilva@swansea.ac.uk.
authors.forename: Lindsay
authors.initials: L
authors.lastname: D'Silva
authors.affiliation: School of Medicine, Swansea University, Swansea, UK. m.j.lawrence@swansea.ac.uk.|NISCHR Haemostasis Biomedical Research Unit, Morriston Hospital, ABMU Health Board, Swansea, SA6 6NL, UK. m.j.lawrence@swansea.ac.uk.
authors.forename: Matthew
authors.initials: M
authors.lastname: Lawrence
authors.affiliation: School of Applied Sciences, Cardiff Metropolitan University, Cardiff, UK. KMorris@cardiffmet.ac.uk.
authors.forename: Roger H K
authors.initials: RH
authors.lastname: Morris
authors.affiliation: NISCHR Haemostasis Biomedical Research Unit, Morriston Hospital, ABMU Health Board, Swansea, SA6 6NL, UK. sharon.storton@wales.nhs.uk.
authors.forename: Sharon
authors.initials: S
authors.lastname: Storton
authors.affiliation: College of Engineering, Swansea University, Swansea, UK. M.R.Brown@swansea.ac.uk.
authors.forename: Martyn Rowan
authors.initials: MR
authors.lastname: Brown
authors.affiliation: NISCHR Haemostasis Biomedical Research Unit, Morriston Hospital, ABMU Health Board, Swansea, SA6 6NL, UK. VanessaJane.Evans@wales.nhs.uk.
authors.forename: Vanessa
authors.initials: V
authors.lastname: Evans
authors.affiliation: School of Medicine, Swansea University, Swansea, UK. K.M.Hawkins@swansea.ac.uk.
authors.forename: Karl
authors.initials: K
authors.lastname: Hawkins
authors.affiliation: College of Engineering, Swansea University, Swansea, UK. P.R.Williams@swansea.ac.uk.
authors.forename: Phylip Rhodri
authors.initials: PR
authors.lastname: Williams
authors.affiliation: Department of Haematology, Royal Brompton Hospital, Royal Brompton and Harefield NHS Foundation Trust, London, UK. S.Davidson@rbht.nhs.uk.
authors.forename: Simon J
authors.initials: SJ
authors.lastname: Davidson
authors.affiliation: Department of Stroke Medicine, Morriston Hospital, Swansea, UK. Mushtaq.Wani@wales.nhs.uk.
authors.forename: Mushtaq
authors.initials: M
authors.lastname: Wani
authors.affiliation: Norwich Medical School, University of East Anglia, Norwich, UK. john.potter@uea.ac.uk.
authors.forename: John F
authors.initials: JF
authors.lastname: Potter
authors.affiliation: School of Medicine, Swansea University, Swansea, UK. phillip.evans2@wales.nhs.uk.|NISCHR Haemostasis Biomedical Research Unit, Morriston Hospital, ABMU Health Board, Swansea, SA6 6NL, UK. phillip.evans2@wales.nhs.uk.|The Emergency Department, Morriston Hospital, ABMU Health Board, Swansea, UK. phillip.evans2@wales.nhs.uk.
authors.forename: Phillip A
authors.initials: PA
authors.lastname: Evans
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D001241:Aspirin / Q000627:therapeutic use; D016022:Case-Control Studies; D015331:Cohort Studies; D004548:Elasticity; D005260:Female; D005340:Fibrinogen / Q000378:metabolism; D005343:Fibrinolytic Agents / Q000627:therapeutic use; D017709:Fractals; D006801:Humans; D008297:Male; D008875:Middle Aged; D011446:Prospective Studies; D020521:Stroke / Q000097:blood* / Q000188:drug therapy; D013927:Thrombosis / Q000097:blood* / Q000188:drug therapy; D010959:Tissue Plasminogen Activator / Q000627:therapeutic use; D014914:Whole Blood Coagulation Time
chemical_list: D005343:Fibrinolytic Agents; D005340:Fibrinogen; D010959:Tissue Plasminogen Activator; D001241:Aspirin