title: The Effects of Temperature on Clot Microstructure and Strength in Healthy Volunteers.
abstract: BACKGROUND
  Anesthesia, critical illness, and trauma are known to alter thermoregulation, which can potentially affect coagulation and clinical outcome. This in vitro preclinical study explores the relationship between temperature change and hemostasis using a recently validated viscoelastic technique. We hypothesize that temperature change will cause significant alterations in the microstructural properties of clot.
  
  
  METHODS
  We used a novel viscoelastic technique to identify the gel point of the blood. The gel point identifies the transition of the blood from a viscoelastic liquid to a viscoelastic solid state. Furthermore, identification of the gel point provides 3 related biomarkers: the elastic modulus at the gel point, which is a measure of clot elasticity; the time to the gel point (TGP), which is a measure of the time required to form the clot; and the fractal dimension of the clot at the gel point, df, which quantifies the microstructure of the clot. The gel point measurements were performed in vitro on whole blood samples from 136 healthy volunteers over a temperature range of 27°C to 43°C.
  
  
  RESULTS
  There was a significant negative correlation between increases in temperature, from 27°C to 43°C, and TGP (r = -0.641, P < 0.0005). Conversely, significant positive correlations were observed for both the elastic modulus at the gel point (r = 0.513, P = 0.0008) and df (r = 0.777, P < 0.0005) across the range of 27°C to 43°C. When temperature was reduced below 37°C, significant reductions in df and TGP occurred at ≤32°C (Bonferroni-corrected P = 0.0093) and ≤29°C (Bonferroni-corrected P = 0.0317), respectively. No significant changes were observed when temperature was increased to >37°C.
  
  
  CONCLUSIONS
  This study demonstrates that the gel point technique can identify alterations in clot microstructure because of changes in temperature. This was demonstrated in slower-forming clots with less structural complexity as temperature is decreased. We also found that significant changes in clot microstructure occurred when the temperature was ≤32°C.
authors.affiliation: From the *NISCHR Haemostasis Biomedical Research Unit, Morriston Hospital, Abertawe Bro Morgannwg University Health Board, Swansea, Wales, United Kingdom; †College of Medicine, Swansea University, Swansea, Wales, United Kingdom; ‡The Welsh Centre for Burns and Plastic Surgery, Morriston Hospital, Swansea, Wales, United Kingdom; §Emergency Department, Morriston Hospital, Abertawe Bro Morgannwg University Health Board, Swansea, Wales, United Kingdom; ‖School of Health Science, Cardiff Metropolitan University, Cardiff, Wales, United Kingdom; and ¶College of Engineering, Swansea University, Swansea, Wales, United Kingdom.
authors.forename: Matthew James
authors.initials: MJ
authors.lastname: Lawrence
authors.forename: Nick
authors.initials: N
authors.lastname: Marsden
authors.forename: Rangaswamy
authors.initials: R
authors.lastname: Mothukuri
authors.forename: Roger H K
authors.initials: RH
authors.lastname: Morris
authors.forename: Gareth
authors.initials: G
authors.lastname: Davies
authors.forename: Karl
authors.initials: K
authors.lastname: Hawkins
authors.forename: Daniel J
authors.initials: DJ
authors.lastname: Curtis
authors.forename: Martin Rowan
authors.initials: MR
authors.lastname: Brown
authors.forename: Phylip Rhodri
authors.initials: PR
authors.lastname: Williams
authors.forename: Phillip Adrian
authors.initials: PA
authors.lastname: Evans
mesh_terms: D001777:Blood Coagulation; D001780:Blood Coagulation Tests; D003198:Computer Simulation; D055119:Elastic Modulus; D005337:Fibrin / Q000378:metabolism* / Q000648:ultrastructure; D017709:Fractals; D005782:Gels; D064368:Healthy Volunteers; D006801:Humans; D008954:Models, Biological; D013696:Temperature; D013997:Time Factors; D014783:Viscosity
chemical_list: D005782:Gels; D005337:Fibrin