title: A new structural biomarker that quantifies and predicts changes in clot strength and quality in a model of progressive haemodilution.
abstract: BACKGROUND
  We investigated the effect of progressive haemodilution on the dynamics of fibrin clot formation and clot microstructure using a novel rheological method. The technique measures clotting time (TGP), clot strength (G`GP), and quantifies clot microstructure (df) at the incipient stages of fibrin formation. We use computational modelling to examine the relationship between structure and mass, as well as helium ion microscopy (HIM) to compare morphological changes in the fully formed clot to that of the incipient clot.
  
  
  METHODS
  This is an in vitro study; 90 healthy volunteers were recruited with informed consent and a 20ml sample of whole blood obtained from each volunteer. Five clinically relevant dilutions were investigated using 0.9w.v isotonic saline (0, 10, 20, 40 and 60%, n=18 for each dilution). The rheological method of assessing structural clot changes was compared against conventional coagulation screen and fibrinogen estimation.
  
  
  RESULTS
  Fractal dimension (df) and final clot microstructure both decreased with progressive dilution (significant at a dilution of 20%) with similar relationships observed for final clot characteristics in HIM images. Significant correlations were observed between df and G`GP (clot strength) (0.345, p=0.02), as well as clotting time (PT: -0.690, p>0.001; APTT: -0.672, p>0.001; TGP: -0.385, p=0.006).
  
  
  CONCLUSIONS
  This study provides new insight into the effects of haemodilution by isotonic saline on clotting time (TGP), clot strength (G'GP) and clot microstructure (df). Previous studies have attempted to link clot microstructure to clot quality/strength, however this study provides a significant step in quantifying these relationships.
authors: NISCHR Haemostasis Biomedical Research Unit, Morriston Hospital, Abertawe Bro Morgannwg University Health Board, Swansea, UK; NISCHR Haemostasis Biomedical Research Unit, College of Medicine, Swansea University, Swansea, UK.
authors: Matthew J
authors: MJ
authors: Lawrence
authors: Emergency Department, Morriston Hospital, Abertawe Bro Morgannwg University Health Board, Swansea, UK.
authors: Sendhil
authors: S
authors: Kumar
authors: NISCHR Haemostasis Biomedical Research Unit, College of Medicine, Swansea University, Swansea, UK.
authors: Karl
authors: K
authors: Hawkins
authors: ECS, Faculty of Physical and Applied Sciences, University of Southampton, Southampton, UK.
authors: Stuart
authors: S
authors: Boden
authors: ECS, Faculty of Physical and Applied Sciences, University of Southampton, Southampton, UK.
authors: Harvey
authors: H
authors: Rutt
authors: NISCHR Haemostasis Biomedical Research Unit, Morriston Hospital, Abertawe Bro Morgannwg University Health Board, Swansea, UK.
authors: Gavin
authors: G
authors: Mills
authors: NISCHR Haemostasis Biomedical Research Unit, Morriston Hospital, Abertawe Bro Morgannwg University Health Board, Swansea, UK; NISCHR Haemostasis Biomedical Research Unit, College of Medicine, Swansea University, Swansea, UK.
authors: Ahmed
authors: A
authors: Sabra
authors: School of Applied Science, University of Wales Institute Cardiff, Cardiff, UK.
authors: Roger H K
authors: RH
authors: Morris
authors: Department of Haematology, Royal Brompton Hospital, Royal Brompton and Harefield NHS Foundation Trust, London, UK.
authors: Simon J
authors: SJ
authors: Davidson
authors: College of Engineering, Swansea University, Swansea, UK.
authors: Nafieseh
authors: N
authors: Badiei
authors: College of Engineering, Swansea University, Swansea, UK.
authors: Martin R
authors: MR
authors: Brown
authors: College of Engineering, Swansea University, Swansea, UK.
authors: Phylip R
authors: PR
authors: Williams
authors: NISCHR Haemostasis Biomedical Research Unit, Morriston Hospital, Abertawe Bro Morgannwg University Health Board, Swansea, UK; NISCHR Haemostasis Biomedical Research Unit, College of Medicine, Swansea University, Swansea, UK; Emergency Department, Morriston Hospital, Abertawe Bro Morgannwg University Health Board, Swansea, UK. Electronic address: phillip.evans2@wales.nhs.uk.
authors: Phillip A
authors: PA
authors: Evans
mesh_terms: D015415:Biomarkers / Q000097:blood / Q000378:metabolism; D001777:Blood Coagulation; D001780:Blood Coagulation Tests; D003198:Computer Simulation; D005337:Fibrin / Q000378:metabolism / Q000648:ultrastructure*; D005340:Fibrinogen / Q000378:metabolism / Q000648:ultrastructure; D017709:Fractals; D006438:Hemodilution / Q000379:methods*; D006801:Humans; D008954:Models, Biological; D012212:Rheology / Q000379:methods; D012965:Sodium Chloride / Q000378:metabolism
chemical_list: D015415:Biomarkers; D012965:Sodium Chloride; D005337:Fibrin; D005340:Fibrinogen
keywords: Dilution; Fluid resuscitation; Fractal dimension; Microstructure