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Fellowship Research Project Funded in 2006

Evaluation of thromboelastography (TEG) as a tool in monitoring the effect of recombinant factor VIIa in hemophilia A animal models

Dr Maha Ahmed Othman
Université Queen’s, Kingston, Ontario

Despite similar factor levels, hemophiliacs often display variable tendencies for bleeding and heterogenous responses to FVIII therapy. To date, no routinely used coagulation assay has proven ideal in predicting the bleeding pattern in hemophilia or reflecting the individual patient’s response to therapy. Conventional assays typically use clot formation as the end point and underestimate the impact of other components of the hemostatic process. Thromboelastography (TEG) is a global assay that assesses the quality of the blood clot and monitors different aspects of the hemostatic process. It provides information about the kinetics of the blood clot and thus a more comprehensive picture of coagulation than standard tests. Recombinant coagulation factor VIIa (rFVIIa) (Novoseven)TM is a safe and effective treatment for hemophilia A and B patients with inhibitors. However, laboratory monitoring of the therapeutic efficacy of this product is still a problem. Bleeding risk does not correlate well with the standard clotting tests and the treatment response also cannot be adequately monitored.

In this study, we have two major goals:1) to investigate the TEG pattern in hemophilia A animal models with and without inhibitors and evaluate the sensitivity of this test to variations in clinical phenotype.2) to evaluate changes in the TEG pattern following administration of rFVIIa in therapeutic doses to these animals and to correlate this to clinical phenotype correction.

These studies have the potential to significantly improve our understanding of the clinical heterogeneity among hemophiliacs. This may help predict individual bleeding risks and improve the laboratory monitoring of rFVIIa therapy.