JGH INSIDER Spring 2018 Article

Grand Opening of New Centre of Excellence in Thrombosis and Anticoagulation Care (CETAC)
Leading the Way in Patient Care, Research and Training Related to Blood Clots and Anticoagulation Safety

Dr. Mark Blostein and Dr. Susan Kahn in the Centre’s beautiful and spacious new waiting area.

A new, expanded Centre of Excellence in Thrombosis and Anticoagulation Care (CETAC) opened in February at the JGH, setting the stage for enhanced awareness, prevention, research, training, diagnosis and treatment of thrombosis and its associated complications, not only at the JGH but across the Quebec health care system.

Thrombosis refers to the formation of blood clots inside a blood vessel that affects 1 to 2 percent of the population. A common complication is venous thromboembolism (VTE), in which a blood clot develops in a large vein. The most common form of VTE is deep vein thrombosis (DVT), a blood clot in the deep veins of the leg or pelvis, which can result in pain, swelling, redness and warmth in the affected leg. In some cases, there may be no outward symptoms. The most dangerous, and potentially life-threatening, form of VTE is pulmonary embolism (PE), wich occurs when a blood clot travels from the legs to the lungs, causing an individual to experience stabbing chest pains, coughing, difficulty breathing, and a rapid pulse. This affects an average of 30,000 Canadian each year. Thrombosis can also occur in the brain (stroke), heart (myocardial infarction) and peripheral arteries (acute limb ischemia).

“Up to 60 percent of VTE cases occur during hospitalization or in the 6-week period post-discharge, making it a leading cause of hospital-associated disability and even death,” says Dr. Susan Kahn, a leading international expert in VTE, who is the founder and director of the CETAC.

Indeed, most hospitalized patients have at least one risk factor for VTE, and two-thirds have three or more risk factors. These can include: a personal or family history of a clotting disorder or DVT, recent major surgery (especially abdominal or orthopaedic) or injury, long periods of immobility, cancer and cancer treatments, pregnancy and the postpartum period, obesity, and various medical illnesses. Each year approximately 2,000 patients with suspected venous thrombosis, 600 patients with confirmed DVT and 150 patients with PE are evaluated and treated at the JGH.

Furthermore, people with VTE have a risk of developing chronic symptoms. For example, about 30 percent of patients with DVT experience what is called the post-thrombotic syndrome (PTS), in which the pain, swelling and heaviness that initially accompany a DVT can linger for months or even years. In the case of PE, some patients can experience lingering shortness of breath and a lower tolerance for exercise. In all cases, these chronic symptoms can reduce one’s quality of life, and one’s ability to work or even perform normal daily activities. Finally, individuals who have an initial episode of VTE are at greater risk of further episodes.

“The good news is that blood clots are preventable and treatable if discovered early,” says Dr. Kahn. “Although there are many risk factors, with proper attention to prevention and treatment, we can reduce the incidence and recurrence of VTE and its complications.” This emphasizes the importance of concerted efforts to train physicians— especially those working in high-risk settings such as primary care offices, emergency rooms, inpatient medi- cal and surgical wards and intensive care units—and to educate the public at large and patients to ensure early diagnosis.

The CETAC is one of only three Royal College-approved training sites in thrombosis in Canada and has attracted trainees from all over the world through its unique Thrombosis Fellowship program. There are currently two fellows doing one year of clinical training at the CETAC, one from Sherbrooke and the other from Kuwait.

“The primary method of preventing VTE is by giving the patient small doses of blood-thinning medication to keep clots from forming,” says Dr. Mark Blostein, Associate Chief of the JGH Division of Hematology and Oncology, and Senior Investigator at the Lady Davis Institute (LDI). “Common examples include Coumadin, an anticoagulant used to prevent strokes and to treat VTE, and various heparins. New oral anticoagulants have recently been developed, but much needs to be learned about these new drugs—emphasizing the need for additional research. While effective, all anticoagulants must be closely monitored because of their potential to cause serious bleeding.”

The JGH was among the first in Canada to develop a hospital-wide protocol to determine which patients are at risk for VTE and which preventive methods should be applied. Since 1998, the JGH has built a unique, multidisciplinary Thrombosis Program with patient care, training, education and internationally recognized research components that are unparalleled in Quebec and among the top three programs in Canada. “We have been trailblazers in developing VTE prevention protocols and anticoagulation guidelines at the national and international level,” confirms Dr. Kahn. “In 2011, our VTE team was presented with the Safer Healthcare Now! Venous Thromboembolism Prevention Hospital Award in recognition of our significant commitment to prevent VTE and achieve outstanding outcomes.” (Safer Healthcare Now! is the flagship program of the Canadian Patient Safety Institute – Editor’s note).

To build on the successes of its Thrombosis Program and broaden its scope, the JGH implemented the initial stages leading to the creation of the CETAC in December 2012. Funding was made possible thanks to the support of private donors, through the JGH Foundation, and a sizeable contribution from pharmaceutical company and partner Sanofi Canada over a period of four years. The CETAC’s mandate is to provide leadership and guidance to other institutions in Quebec, to support local initiatives in thrombosis prevention and treatment, develop and disseminate best practice guidelines, and support thrombosis-related clinical decision making, thereby improving patient outcomes.

“However, we didn’t have a dedicated facility, nor the funding to do everything that we envisioned,” recalls Dr. Blostein. “Patients were spilling in the corridors owing to the insufficient number of exam rooms and waiting areas. We didn’t have the room to hire an anticoagulant pharmacist, or to train physicians (fellows) and graduate students. Our clinical team, our researchers and even our services were scattered throughout the hospital.”

“All of that changed this year, thanks once more to our fruitful partnership with Sanofi Canada and the generous support from the community,” gratefully acknowledges Dr. Kahn.

“Sanofi is proud to support the Centre of Excellence in Thrombosis and Anticoagulation Care (CETAC) at the Jewish General Hospital as part of our commitment to investing in initiatives that empower the lives of Canadians. It is an important priority for Sanofi to contribute to patient education and our goal is to help patients and their families when it matters the most,” said Paul-François Cossa, General Manager of Sanofi GEM Canada.

Located on the third floor of Pavilion B, the new, expanded CETAC regroups all clinical, training and research activities in a single, dedicated location. It includes:

• The Thrombosis Clinic, which offers an integrated, multidisciplinary approach to the diagnosis, management and treatment of patients who have had or are at risk of thrombosis. It receives roughly 4,000 patient visits per year, with numerous referrals for issues pertaining to the screening of blood clots, pregnancy-related complications, recurrent or unusual blood clots in an artery, and long term complications such as post-thrombotic syndrome;
• The Anticoagulation Clinic, which provides care to patients who are taking blood thinning medication, often for life, and receives 20,000 patient-visits per year;
• The Inpatient Thrombosis Consultation Service, which receives an average of 6 to 10 requests per day for consultations on hospitalized patients on various aspects of thrombosis and anticoagulation management;
• The DOAC Clinic, specializing in the management of patients taking DOACs (direct oral anticoagulants), which in many instances are better and safer than Coumadin. The CETAC is the only centre in Quebec to have performed research on antidotes to these new anticoagulants;
• The thrombosis research team, which includes researchers from the Epidemiology Axis at the Lady Davis Institute (LDI), as well as research assistants and support staff;
• Offices for the physicians who make up the CETAC’s clinical team, namely: Dr. Mark Blostein; Dr. Susan Kahn; Dr. Maral Koolian, Internist; and Dr. Vicky Tagalakis, Clinical Epidemiologist and Internist, Associate Director, Centre for Clinical Epidemiology at the LDI. Dr. Andrew Hirsch, Chief of the JGH Division of Pulmonary Medicine and Investigator at the LDI, is the fifth member of the team but his office is located in the premises of the Division he heads.

The facility also features six examination rooms, a training room, a specially designed conference room, separate space for clinical research, and spacious waiting rooms. “Our services are more accessible for patients with walking aids or in wheelchairs,” adds Dr. Blostein. “Patients are very happy with the new, more dignified space.”

Support from private donors also will enable the hiring of a designated anticoagulation pharmacist, as well as the acquisition of much-needed equipment such as oximeters –a non-invasive tool for monitoring a person’s oxygen saturation, high quality scales (as some drugs are dosed by weight) and x-ray viewers to view pulmonary scans.

“We are now in a position to expand our clinical activities and increase our recruitment of patients in thrombosis studies,” declares Dr. Kahn. “The added space also will allow us to measure outcomes via patient satisfaction surveys and other means. These are critical to assess which pharmacologic and non-pharmacologic measures actually diminish the risk of DVT and PE, and to the continuous improvement of our interventions.”

Benefits arising from the establishment of the CETAC in a dedicated and expanded facility include streamlined care delivery, improved workflow and strengthened research collaboration. Concerted attention to clinical care, education and research in anticoagulation safety will improve the health of the many patients at the JGH who need to take blood thinner medications.

“The Centre of Excellence in Thrombosis and Anticoagulation Care will play a vital role in lessening thrombosis-related mortality, morbidity and socioeconomic burden not only here at the JGH but throughout the Quebec healthcare system,” concludes Dr. Kahn.

Key Facts

• Up to 60,000 patients are hospitalized each year for deep vein thrombosis (DVT) in Canada
• 40%of hospitalized patients have three or more risk factors for venous thromboembolism
• 20% of patients diagnosed and treated for thrombosis at the JGH are cancer patients
• 5% is 30-day case fatality rate for DVT
• In the elderly, DVT is associated with a 21% one-year mortality rate
• 33% is 30-day case fatality rate for pulmonary embolism (PE)
• In the elderly, PE is associated with a 39% one-year mortality rate
• Massive pulmonary embolism is the cause of death in approximately 10% of hospitalized patients; it generally occurs without any warning and without the opportunity to intervene
• Untreated PE has a mortality rate approaching 25%
• 1 in 7 cancer patients undergoing treatment in a hospital dies because of pulmonary embolism
• PE is the leading cause of maternal death associated with childbirth. A woman’s risk of developing Venous Thromboembolism (VTE) is six times greater when she is pregnant
• A third of the people (33%) with DVT/PE will have a recurrence within 10 years

Finding new and safer treatments for VTE

Anticoagulants are the standard of care for preventing and treating venous thromboembolism (VTE). Unfortunately, their association with severe bleeding makes them an imperfect remedy. At the Lady Davis Institute (LDI), fundamental research is on-going to better understand the cellular components of VTE in the hope of discovering novel drugs that will treat thrombosis but not cause excessive bleeding.

Dr. Mark Blostein is a clinician-scientist whose lab at the LDI is exploring the potential of manipulating the protein Gas6 to better control blood clots. Gas6 has demonstrated anti-сlotting properties without inducing bleeding.

“Our lab is interested in delving down into the cellular components of VTE in order to discover alternative treatments that will minimize the complications of VTE and the use of blood thinners,” Dr. Blostein explains. “Our hypothesis is that the development of an inhibitor to Gas6 will interfere with the accumulation of white blood cells that contribute to the damage caused by VTE, including post-thrombotic syndrome, chronic lung disease, and death from pulmonary embolism. It has been shown in animal models that targeting Gas6 does not cause bleeding, making it promising for adjuvant therapy to anticoagulants that may have a positive impact on the long-term complications of VTE.”

This is an example of the kind of basic biological research that is crucial for the eventual development of new drugs that will benefit patients in the clinic.

The Canadian Venous thromboembolism Clinical trials and outcomes Research network

In recognition of the importance of offering effective treatment and conducting research to improve therapies with regard to VTE, the Canadian Institutes of Health Research (CIHR), the Fonds de recherche Québec – Santé (FRQS), and a consortium of public and private funders, including the Lady Davis Institute (LDI) at the Jewish General Hospital (JGH), McGill University, and the Ottawa Hospital and University of Ottawa have joined forces to create the Canadian Venous Thromboembolism Clinical Trials and Outcomes Research Network (known as CanVECTOR). Dr. Susan Kahn is co-director and co-principal investigator, along with Dr. Marc Rodger of the Ottawa Hospital.

CanVECTOR’s objectives include reducing VTE occurrence, improving VTE diagnosis and therapeutic management, improving the safety of anticoagulant delivery, and enhancing the quality of life of those impacted by VTE, both in Canada and globally. The network incorporates clinician-scientists, basic researchers, nurses, health economists, methodologists, as well as patient partners based at universities and hospitals across nine provinces. It is rather innovative to include patients when designing research questions, but crucial as they have unique insight into the aspects of disease that are of most concern to their particular circumstance.

“We are determined to focus on questions that can be translated into clinical practice so that our research will have a direct impact on public health,” said Dr. Kahn.

A hub for thrombosis Research

On any given day, between 60 and 65 percent of inpatients at the JGH are on some form of anticoagulation medication, which must be closely monitored in order to combat side effects.

“Venous thromboembolism (VTE) is the third most common cardiovascular condition after heart attack and stroke,” said Dr. Kahn. “In addition, pulmonary embolism causes more deaths each year than breast cancer, HIV and motor vehicle accidents combined. These complications are serious health issues, which must be addressed in a concerted fashion within a dedicated facility.”

Thrombosis experts at the LDI are frequently sought as collaborators by researchers at other institutions. The JGH is a highly regarded site for participation in clinical trials by pharmaceutical companies, as well as investigator-initiated studies.

For example, JGH patients were part of a recent multicentre, double-blind, randomized, controlled clinical trial showing that aspirin was as effective as rivaroxaban, the standard anticoagulation medication, at preventing VTE following hip and knee replacement surgeries. The study was published in the prestigious New England Journal of Medicine. Thanks to its established expertise in thrombosis treatment and research, alongside its well-regarded orthopedics service, the JGH was well suited for inclusion in this important study that could contribute to changing the standard of care for patients.

“The protocols for preventing blood clots following major orthopedic surgery are well established. However, we are always interested in determining whether there are better options for treating our patients. We could well see aspirin emerge as a practical alternative to more expensive anticoagulants,” Dr. Kahn, one of the study’s authors, said.

CETAC positions the Lady Davis Institute as a magnet to attract trainees as well as established scientists and financial resources. As a hub for thrombosis research, CETAC serves as a valuable resource for information and knowledge transfer for other institutions in fulfillment of the goal of reducing the incidence of VTE and improving patient safety and outcomes.