Summary of Research Program
Dr. Siegal’s research program aims to improve the outcomes of patients with cardiovascular disease by optimizing the use of antithrombotic therapies in the following areas: 1) Management of anticoagulant-related bleeding complications; 2) Prevention of anticoagulant-related gastrointestinal bleeding; 3) Perioperative management and outcomes of anticoagulated patients requiring urgent (unplanned) surgery; 4) Epidemiology, antithrombotic management and outcomes of patients with cancer who experience ischemic stroke; and 5) Reducing iatrogenic blood loss and transfusion in critically ill patients.

Selected Research Contributions as Principal Investigator
1. Dr. Siegal had a significant role in the clinical development of andexanet alfa for the reversal of factor Xa inhibitor anticoagulants, including leading the ANNEXA-A/-R studies and analysis and publication of the ANNEXA-4 studies published in the New England Journal of Medicine (2015, 2016, 2019).

2. Post-Bleed Management of Antithrombotic Therapy (PANTHER) research program: Funded by HSFC/CanVECTOR, ASH, CIHR, this series of studies aims to develop an evidence-based strategy for restarting anticoagulants after bleeding, an area of substantial uncertainty with no high-quality evidence to inform clinical decision-making. Ongoing PANTHER studies include the PANTHER-GI Pilot Study evaluating a thrombosis-risk adapted strategy for restarting anticoagulation after major gastrointestinal (GI) bleeding, and PANTHER-VP mixed-methods study which is evaluating patient/caregiver values and preferences regarding restarting anticoagulation after GI bleeding.

3. Perioperative Anticoagulant Use for Surgery Evaluation - Emergency Registry (PAUSE-ER): An international multi-centre prospective cohort study evaluating outcomes of anticoagulated patients requiring urgent procedures.

4. Small-Volume Tubes to Reduce Anemia and Transfusion (STRATUS) study: A stepped wedge cluster randomized trial conducted at 25 hospitals in Canada evaluating whether small-volume blood collection tubes reduce red blood cell transfusion in critically ill patients.

5. Venous Thrombosis Virtual Surveillance in COVID (VVIRTUOSO): Prospective cohort study evaluating the incidence of venous thromboembolism after hospitalization for COVID-19. 

6. Intensive Cancer Screening after Cryoptogenic Stroke (INCOGNITO): Pilot randomized trial assessing the feasibility of a definitive randomized trial to evaluate whether FDG PET/CT in addition to usual care increases the number of occult cancers detected in patients with cryptogenic ischemic stroke compared to usual care alone.