The Prix Galien Research Award has been given to Dr. John Kelton and Dr. Theodore Warkentin of McMaster University.
Dr. John Kelton has been Dean of Health Sciences, Vice-President (Health Sciences) and the Dean of the School of Medicine at McMaster University since 2001. Dr. Theodore Warkentin is a Professor of Pathology and Molecular Medicine at McMaster University and began his research career in Dr. Kelton’s laboratory.
This team has devoted a good portion of their research careers examining the mechanism, manifestations, diagnosis and possible treatments for heparin-induced thrombocytopenia (HIT). This work has had important impact on the clinical use of heparin. The team was responsible for the development of the “gold standard” test known as the serotonin release assay to diagnose HIT. Although HIT was initially felt to be a rare adverse response to treatment with heparin, Kelton and Warkentin demonstrated that 1 – 5% of patients treated with heparin for more than one week could present with thrombocytopenia and/or thrombosis. The risk of developing HIT depends on the type of heparin used - unfractionated heparin having the highest likelihood, low-molecular weight heparin having a much lower risk and fondaparinux (a complex polysaccharide with anticoagulant activity) having a negligible risk. Despite the reduced platelet count, HIT is an intensely prothrombotic disorder with venous thrombosis being more common than arterial thrombosis but both can lead to gangrene.
Dr. Theodore Warkentin, Dr. Jean Gray, President of the Jury, Cheryl Cann and Dr. John
Kelton and Warkentin worked out the pathophysiology of the disorder. They demonstrated that about 5 to 40% of patients treated with heparin develop antiplatelet factor 4 heparin antibody complexes about 4 – 5 days after heparin exposure and that these complexes bind to platelet receptors, resulting in a variety of manifestations including venous gangrene (particularly if warfarin is substituted for heparin) delayed onset HIT, transient global amnesia and adrenal hemorrhagic necrosis.
In addition, their work has focused on possible treatments for HIT and has included the development and testing of several molecules such as argatroban and, more recently, fondaparinux for the treatment of HIT. Current cardiology guidelines recommend the use of fondaparinux rather than heparin during cardiac catheterization procedures, a major shift in recommendation because of this research.
The work performed by this team has resulted in numerous major awards from international transfusion and hematology organizations. An impressive number of students and fellows have passed through their laboratories and continued working in the areas of coagulation and thrombosis. In addition, Drs. Kelton and Warkentin, both together and individually, have made substantial contributions to the wider field of platelet disorders.
For their careful studies of heparin-induced thrombocytopenia over several decades and for transforming the care of patients who experience this disorder, the Prix Galien Research Award for 2015 is awarded to Drs. John Kelton and Theodore Warkentin of McMaster University.