title: A comprehensive study of ovine haemostasis to assess suitability to model human coagulation.
abstract: BACKGROUND
  Similarities in size, anatomy and physiology have supported the use of sheep to model a wide range of human diseases, including coagulopathy. However, coagulation studies involving sheep are limited by the absence of high quality data defining normal ovine coagulation and fibrinolysis.
  
  
  METHODS
  Full blood examination, routine and specialised coagulation tests, rotational thromboelastometry and whole blood platelet aggregometry was performed on 50 healthy Samm & Border Leicester Cross ewes and compared to corresponding human ranges. Intraspecies breed and gender variability was investigated by comparison to a smaller population of 13 healthy Merino wethers.
  
  
  RESULTS
  Ovine coagulation was similar to human according to routine coagulation methods (PT, aPTT, TCT, Fib(C)) and some specialised coagulation tests (vWF, AT, Plasmin Inh). Despite these similarities, ovine secondary haemostasis demonstrated substantial differences to that of human. Rapid initiation of the contact activation pathway, high levels of FVIII, low Protein C, greater overall clot firmness and a reduced capacity for clot lysis was documented in sheep. In addition, ADP and collagen agonists precipitated a reduced primary haemostatic response in sheep relative to human. Intraspecies differences in whole blood platelet aggregometry between the cohorts of sheep indicate the need for breed-specific normal ranges.
  
  
  CONCLUSIONS
  The application of a board spectrum of coagulation assays has enabled elucidation of the similarities as well as differences between ovine and human coagulation. The new knowledge generated from this study will guide the design of future translational coagulation studies in ovine models.
authors.affiliation: Critical Care Research Group, The University of Queensland and The Prince Charles Hospital, Brisbane, QLD, Australia. Electronic address: samuelrfoley@gmail.com.
authors.forename: Samuel R
authors.initials: SR
authors.lastname: Foley
authors.affiliation: Pathology Queensland, Princess Alexandra Hospital, Brisbane, QLD, Australia.
authors.forename: Connie
authors.initials: C
authors.lastname: Solano
authors.affiliation: Critical Care Research Group, The University of Queensland and The Prince Charles Hospital, Brisbane, QLD, Australia; Research and Development, Australian Red Cross Blood Service, Brisbane, QLD, Australia.
authors.forename: Gabriela
authors.initials: G
authors.lastname: Simonova
authors.affiliation: Pathology Queensland, Princess Alexandra Hospital, Brisbane, QLD, Australia.
authors.forename: Michelle M
authors.initials: MM
authors.lastname: Spanevello
authors.affiliation: Pathology Queensland, Princess Alexandra Hospital, Brisbane, QLD, Australia; School of Medicine, Griffith University, QLD, Australia.
authors.forename: Robert J
authors.initials: RJ
authors.lastname: Bird
authors.affiliation: Keenan Research Centre, Li Ka Shing Knowledge Institute, St. Michael's Hospital, Toronto, ON, Canada.
authors.forename: John W
authors.initials: JW
authors.lastname: Semple
authors.affiliation: School of Medical Sciences, RMIT University, Bundoora, VIC, Australia.
authors.forename: Denise E
authors.initials: DE
authors.lastname: Jackson
authors.affiliation: Mater Children's Hospital Mater, The University of Queensland, Brisbane, QLD, Australia.
authors.forename: Andreas
authors.initials: A
authors.lastname: Schibler
authors.affiliation: Critical Care Research Group, The University of Queensland and The Prince Charles Hospital, Brisbane, QLD, Australia.
authors.forename: John F
authors.initials: JF
authors.lastname: Fraser
authors.affiliation: Critical Care Research Group, The University of Queensland and The Prince Charles Hospital, Brisbane, QLD, Australia; School of Health and Sports Science, University of Sunshine Coast, Sippy Downs, QLD, Australia.
authors.forename: Yoke Lin
authors.initials: YL
authors.lastname: Fung
mesh_terms: D000818:Animals; D001780:Blood Coagulation Tests; D005260:Female; D006487:Hemostasis; D006801:Humans; D008297:Male; D023421:Models, Animal; D012756:Sheep / Q000097:blood*
keywords: Animal; Coagulation parameters; Normal values; Platelets; Sheep; Thromboelastometry