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A comprehensive study of ovine haemostasis to assess suitability to model human coagulation

Foley, Samuel R; Solano, Connie; Simonova, Gabriela; Spanevello, Michelle M; Bird, Robert J; Semple, John W LU ; Jackson, Denise E; Schibler, Andreas; Fraser, John F and Fung, Yoke Lin (2014) In Thrombosis Research 134(2). p.73-468
Abstract

INTRODUCTION: 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.

MATERIALS AND 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... (More)

INTRODUCTION: 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.

MATERIALS AND 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.

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author
publishing date
type
Contribution to journal
publication status
published
keywords
Animals, Blood Coagulation Tests, Female, Hemostasis, Humans, Male, Models, Animal, Sheep, Comparative Study, Journal Article, Research Support, Non-U.S. Gov't
in
Thrombosis Research
volume
134
issue
2
pages
6 pages
publisher
Elsevier
external identifiers
  • scopus:84905089855
ISSN
1879-2472
DOI
10.1016/j.thromres.2014.05.026
language
English
LU publication?
no
id
2c355a9a-4dd0-419e-8406-c7f0a7bf664b
date added to LUP
2016-09-23 12:00:05
date last changed
2017-03-10 10:14:18
@article{2c355a9a-4dd0-419e-8406-c7f0a7bf664b,
  abstract     = {<p>INTRODUCTION: 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.</p><p>MATERIALS AND METHODS: Full blood examination, routine and specialised coagulation tests, rotational thromboelastometry and whole blood platelet aggregometry was performed on 50 healthy Samm &amp; 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.</p><p>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.</p><p>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.</p>},
  author       = {Foley, Samuel R and Solano, Connie and Simonova, Gabriela and Spanevello, Michelle M and Bird, Robert J and Semple, John W and Jackson, Denise E and Schibler, Andreas and Fraser, John F and Fung, Yoke Lin},
  issn         = {1879-2472},
  keyword      = {Animals,Blood Coagulation Tests,Female,Hemostasis,Humans,Male,Models, Animal,Sheep,Comparative Study,Journal Article,Research Support, Non-U.S. Gov't},
  language     = {eng},
  number       = {2},
  pages        = {73--468},
  publisher    = {Elsevier},
  series       = {Thrombosis Research},
  title        = {A comprehensive study of ovine haemostasis to assess suitability to model human coagulation},
  url          = {http://dx.doi.org/10.1016/j.thromres.2014.05.026},
  volume       = {134},
  year         = {2014},
}