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

Foley, Samuel R.; Solano, C.; Šimonová, Gabriela; Spanevello, Michelle M.; Bird, Robert; Semple, John W.; Jackson, Denise E.; Schibler, Andreas; Fraser, John F.; Fung, Yoke Lin

doi:10.1016/j.thromres.2014.05.026

Cited by 33 publications

(36 citation statements)

References 35 publications

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“…However there was no associated change in induced platelet aggregation parameters to suggest altered platelet function. Constitutional differences in platelet function may have contributed to this finding as the magnitude of ADP and collagen induced platelet aggregation in sheep is less than half that of humans (59). It is possible that a significant alteration in platelet function did develop, however was unable to be detected by the tests utilised in this thesis.…”

Section: Altered Platelet Function Did Not Contribute To Coagulopathymentioning

confidence: 94%

“…Animal models provide an alternative option as they facilitate the controlled and systematic evaluation of isolated insults in vivo, which may enhance mechanistic understanding and identify novel therapeutic targets. However animals are genetically distinct from humans, and demonstrate differences in coagulation assay parameters, coagulation factor concentrations and platelet function that may alter the susceptibility to ATC (58)(59)(60)(61)(62). For an animal model to be clinically relevant there needs to be more similarities than differences between the human coagulation system and that of the chosen animal species.…”

Section: Intrinsic Pathway Extrinsic Pathwaymentioning

confidence: 99%

“…Comparative studies of human, porcine, rodent, canine and ovine coagulation function using routine coagulation tests, rotational thromboelastometry (ROTEM) and clotting factor assays also suggest that the human coagulation system demonstrates the greatest similarity with that of sheep (58,59). However there are no current published ovine models of ATC.…”

Section: Intrinsic Pathway Extrinsic Pathwaymentioning

confidence: 99%

“…Sheep are genetically distinct from humans, and despite demonstrable similarities in coagulation function also have acknowledged differences in primary and secondary haemostasis that may impact the translatability of findings (58,59). These differences include constitutively different concentrations of coagulation factors, with mean protein C activity that is 60% of human values and mean factor VIII activity that is three times those of humans (59) (table 5).…”

Section: Limitations Of the Model Used In This Thesismentioning

confidence: 99%

“…Sheep share a number of similarities in cardiorespiratory and hemostatic function with humans, demonstrating equivalent values for fibrinogen, aPTT, and ROTEM parameters (58,59,76). These similarities suggest that they may be a suitable species in which to develop an alternative large animal model of ATC.…”

Section: Introductionmentioning

confidence: 99%

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Validation of acute traumatic coagulopathy in an ovine model of trauma and haemorrhage

Zyl¹

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This thesis describes an ovine model of complex trauma and haemorrhage that demonstrates coagulation changes using both traditional plasma based assays and point of care viscoelastic assays that are consistent with current definitions of ATC. The degree of coagulopathy was correlated with the degree of shock as quantified by arterial lactate.Coagulopathy was also associated with activation of the protein C pathway and shedding of the endothelial glycocalyx. Fibrinolysis did not make a significant contribution to the coagulopathy observed and there was no evidence of altered platelet function in this model.ii

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Section: Altered Platelet Function Did Not Contribute To Coagulopathymentioning

confidence: 94%