What We Do
Image shows basic processes of hemostasis and thrombosis. Hemostasis serves to heal wounds in blood vessels and involves a series of reactions that seal the site of injury. Thse steps involve sequential activation of clotting factors (F). Thrombosis represents an over-active hemostasis response due to the presence of injured tissue that releases activating agents such as tissue factor (TF), polyphosphate (PP), or neutrophil extracellular traps (NETS), or due to the presence of medical devices.
Fredenburgh JC, Weitz JI. News at XI: moving beyond factor Xa inhibitors. J Thromb Haemost. 2023 Jul;21(7):1692-1702. doi: 10.1016/j.jtha.2023.04.021.
The Weitz Lab focuses on the regulation of hemostasis, the balance between the processes that promote clot formation (coagulation) and those that promote clot degradation (fibrinolysis). Normally, these systems are balanced such that blood is maintained in a fluid state and flows freely through the vasculature. Numerous regulatory mechanisms maintain this balance, however, dysregulation in either process can cause excessive clotting, which leads to thrombosis or excessive fibrinolysis, which can lead to bleeding.
Thrombosis, which involves abnormal blood clot formation in arteries or veins, is responsible for one in four deaths in Canada and worldwide. Blood clot formation in arteries blocks blood flow and is responsible for heart attack and stroke. Blood clot formation in veins is the underlying cause of deep vein thrombosis. Clots in the deep veins of the leg can break off and travel to the lungs where they plug lung arteries and produce a pulmonary embolism, which can be fatal. A major goal of the Weitz research program is to reduce disability and death caused by thrombosis.
Anticoagulants or “blood thinners” are drugs that attenuate blood clot formation. Anticoagulants are a mainstay for the prevention and treatment of clots in arteries and veins. By attenuating clot formation, the currently available anticoagulants attenuate thrombosis (“bad clots”) by preventing clot formation in arteries or veins. However, they can also cause bleeding by attenuating the formation of clots that plug holes in the blood vessels at sites of injury (“good clots”). A major focus of the Weitz Lab is on the development of safer anticoagulants that attenuate bad clot formation (i.e., thrombosis) without disrupting good clot formation (i.e., hemostasis). Anticoagulants that target factor XI or factor XII are examples of this new class of agents that may be safer than currently available anticoagulants. Studies are underway to better understand how these new agents work and why they are safer than the currently available anticoagulants are underway.
Coagulation can be triggered by damage to or activation of the cells lining the blood vessels, sluggish blood flow,or hypercoagulability of the blood. Medical devices such as catheters, stents or mechanical heart valves can also induce clot formation. The Weitz Lab is investigating these mechanisms. We have identified a protein in the circulation that down regulates clotting induced by medical devices or by clot-promoting substances released from activated blood cells. Studies are underway to determine how this protein shuts down clotting and exploiting this information to develop novel anticoagulants.
On the medical device side, the Weitz Lab is working with bioengineers at McMaster to develop novel coatings that repel protein and blood cell deposition and prevent clotting on the devices. These techniques are being used to design clot resistant catheters, grafts and heart valves.
Finally, the Weitz Lab is investigating a novel approach to attenuating thrombosis by enhancing clot degradation. This can be accomplished by inhibiting the natural blockers of clot breakdown.
Image shows the time-line of development of anticoagulants.
Initial agents were non-specific and targeted multiple factors (F). But with continued research and experience, novel, direct-acting agents have been developed. Agents directed at thrombin and FXa are approved for clinical use, whereas those targeting FXI and FXII are in clinical trials.
Who We Are
The lab is directed by Dr. Jeffrey Weitz at the Thrombosis and Atherosclerosis Research Institute (TaARI), a joint venture between McMaster University and Hamilton Health Sciences. Dr. Weitz is a hematologist and a clinician-scientist. He is a professor in the Departments of Medicine and Biochemistry and Biomedical Sciences and he is the past president of the International Society on Thrombosis and Haemostasis. The lab is located at the David Braley Research Institute at the Hamilton General Hospital site. The research group is comprised of research associates, undergraduate students, graduate students and postdoctoral fellows.
