Research Interests:Hemostasis is the focus of my research. Our lab is interested in three major areas:
Platelet type- von Willebrand disease (PT-VWD):
PT-VWD is a rare platelet defect that shares common clinical and laboratory features with another much more common bleeding disorder known as type 2B VWD. This differentiation is important as it determines the treatment decision. The Canadian- international project that I led was the first international effort to investigate the occurrence of PT-VWD (platelet GPIBA gene defect) and its misdiagnosis with type 2B von Willebrand disease (VWF gene defect). I created an international online database registry www.pt-vwd.com that is well supported by the International Society of Thrombosis and Haemostasis (ISTH). Through dedicated 15 years of work investigating the molecular pathology of PT-VWD we demonstrated two crucial findings: A) PT-VWD is misdiagnosed in 15% of cases of type 2B VWD. B) DNA analysis is required to verify the diagnosis of this disease in addition to the limited standard laboratory methods. A functionally characterised mutation we identified outside the VWF binding region was crucial to highlight a previously non-recognised role for the macroglycopeptide region (site of the mutation) of the GPIb alpha protein. The results of the novel studies in the mouse model carried out by our group at Queen’s have furthered the understanding of the kinetics of thrombus formation and clot structure in the diseased animals. An international RAND-based study to obtain a formal consensus among experts in order to generate international guidelines, for the diagnosis and management of the disease, is currently being conducted.
Thromobelastography (TEG) Applications:
We have been promoting the use and applications of the global haemostatic assay thromboelastography (TEG) in different haematological and non-haematological disorders.
Our studies in haemophilia dogs following acute exercise and in response to rFVIIa treatment supported the value of TEG not only as an effective and early monitoring test, but also as a tool for individualized therapy. Our TEG collaborative studies showed the effectiveness of this tool in obstructive sleep apnea (OSA), initially with a rat model of the disease then via a double blinded study in patients with severe OSA. We demonstrated hypercoagulability can be reversed by CPAP; the standard treatment in the disease.
Our collaborative studies in patients with prostate cancer (PCa) showed PCa patients are hypercoagulable and TEG findings predicted thromboembolic events particularly in those with advanced disease on ADT. Our extended longitudinal study in patients under ADT have revealed new and interesting data about the effect of this classic therapy on the cogulability of patients overtime.
Coagulopathies in pregnancy and placenta mediated complications:
In our collaborative studies in LPS-induced inflmmation model of pre-eclampsia and pregnancy loss, we demonstrated evidence of local placental and systemic maternal coagulopathy in conjunction with maternal inflammation, impaired utero-placental haemodynamics. Modulation of inflammation reduced/prevented prevented inflammation-associated coagulopathies and foetal death. The NO mimetic glyceryl trinitrate (GTN) also prevented foetal death and the inflammation-induced coagulopathies in similar animal models. These studies provide a rationale for GTN in improving maternal/foetal outcomes in some pregnancy mediated complications; something we plan to investigate further.
In assessing women’s coagulopathies, we evlauted TEG in assessing coagulation profile in women with gestational hypertension and pre-eclampsia, in healthy women with different phases of menstruation and in women receiving oral contraception. The latter studies are useful in establishing women’s normal ranges and in introducing a sensitive method to allow personalized contraception. This data also alerts clinicians and investigators about exercising caution when interpreting results of haemostatic tests in females at different phases of menstrual cycle.