Comparison of the effect of coagulation and platelet function
impairments on various mouse bleeding models

Nima Vaezzadeh; Ran Ni; Paul Y. Kim; Jeffrey I. Weitz; Peter L. Gross

doi:10.1160/TH13-11-0919

Thrombosis and Haemostasis, Table of Contents

Thromb Haemost 2014; 112(02): 412-418
DOI: 10.1160/TH13-11-0919

Animal Models

Schattauer GmbH

Comparison of the effect of coagulation and platelet function impairments on various mouse bleeding models

Nima Vaezzadeh

¹Thrombosis and Atherosclerosis Research Institute, McMaster University, Hamilton, Canada

²Department of Medical Sciences, McMaster University, Hamilton, Canada

,

Ran Ni

¹Thrombosis and Atherosclerosis Research Institute, McMaster University, Hamilton, Canada

²Department of Medical Sciences, McMaster University, Hamilton, Canada

,

Paul Y. Kim

¹Thrombosis and Atherosclerosis Research Institute, McMaster University, Hamilton, Canada

³Department of Medicine, McMaster University, Hamilton, Canada

,

Jeffrey I. Weitz

¹Thrombosis and Atherosclerosis Research Institute, McMaster University, Hamilton, Canada

²Department of Medical Sciences, McMaster University, Hamilton, Canada

³Department of Medicine, McMaster University, Hamilton, Canada

⁴Department of Biochemistry and Biomedical Sciences, McMaster University, Hamilton, Canada

,

Peter L. Gross

¹Thrombosis and Atherosclerosis Research Institute, McMaster University, Hamilton, Canada

²Department of Medical Sciences, McMaster University, Hamilton, Canada

³Department of Medicine, McMaster University, Hamilton, Canada

› Author Affiliations

Abstract

Summary

Haemostatic impairments are studied in vivo using one of several murine bleeding models. However it is not known whether these models are equally appropriate for assessing coagulation or platelet function defects. It was our study objective to assess the performance of arterial, venous and combined arterial and venous murine bleeding models towards impaired coagulation or platelet function. Unfractionated heparin (UFH) or α_IIbβ₃ inhibitory antibody (Leo.H4) were administered to mice, and their effects on bleeding in saphenous vein, artery, and tail tip transection models were quantified and correlated with their effects on plasma clotting and ADP-induced platelet aggregation, respectively. All models exhibited similar sensitivity with UFH (EC₅₀ dose = 0.19, 0.13 and 0.07 U/g, respectively) (95% CI = 0.14 – 0.27, 0.08 – 0.20, and 0.03 – 0.16 U/g, respectively). Maximal inhibition of ex vivo plasma clotting could be achieved with UFH doses as low as 0.03 U/g. In contrast, the saphenous vein bleeding model was less sensitive to α_IIbβ₃ inhibition (EC₅₀ = 6.9 µg/ml) than tail transection or saphenous artery bleeding models (EC₅₀ = 0.12 and 0.37 µg/ml, respectively) (95% CI = 2.4 – 20, 0.05 – 0.33, and 0.06 – 2.2 µg/ml, respectively). The EC₅₀ of Leo.H4 for ADP-induced platelet aggregation in vitro (8.0 µg/ml) was at least 20-fold higher than that of the tail and arterial, but not the venous bleeding model. In conclusion, venous, arterial and tail bleeding models are similarly affected by impaired coagulation, while platelet function defects have a greater influence in models incorporating arterial injury.

Keywords

Haemorrhage - experimental animal models - heparin - platelet aggregation inhibitors

Full Text

References

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