Global measurement of coagulation in plasma from normal and haemophilia dogs using a novel modified thrombin generation test – Demonstrated in vitro and ex vivo

Creator

Madsen, Daniel Elenius
- Other Affiliation: Translational Haemophilia Pharmacology; Global Research; Novo Nordisk A/S
Nichols, Timothy C.
- Affiliation: School of Medicine, Department of Pathology and Laboratory Medicine
Merricks, Elizabeth P.
- Affiliation: School of Medicine, Department of Pathology and Laboratory Medicine
Waters, Emily K.
- Other Affiliation: Haemophilia Biology; Global Research; Novo Nordisk A/S
Wiinberg, Bo
- Other Affiliation: Translational Haemophilia Pharmacology; Global Research; Novo Nordisk A/S

Abstract

Canine models of severe haemophilia resemble their human equivalents both regarding clinical bleeding phenotype and response to treatment. Therefore pre-clinical studies in haemophilia dogs have allowed researchers to make valuable translational predictions regarding the potency and efficacy of new anti-haemophilia drugs (AHDs) in humans. To refine in vivo experiments and reduce number of animals, such translational studies are ideally preceded by in vitro prediction of compound efficacy using a plasma based global coagulation method. One such widely used method is the thrombin generation test (TGT). Unfortunately, commercially available TGTs are incapable of distinguishing between normal and haemophilia canine plasma, and therefore in vitro prediction using TGT has so far not been possible in canine plasma material.

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