Study Impacts Clinical Practice


St. Joseph’s Healthcare Hamilton researcher Mark Crowther is interested in blood clots.

“When people ask why, my standard answer is that half of people will die of a blood clot.”

Over the past three decades, the thrombosis community in Hamilton has earned the reputation as world leaders on how blood clots happen and how they are treated. Their work has changed the way that patients are treated everywhere.

Dr. Crowther’s latest research, recently published in the New England Journal of Medicine, adds to that record. The study will change how patients with antiphospholipid antibody syndrome (APLA) are treated.

APLA is a disorder characterized by antibodies that are associated with both arterial and venous thrombosis (clots). APLA antibodies are found in a variety of clinical situations, including patients with lupus or other auto-immune diseases, fetal loss, dementia, and strokes. The antibodies can develop spontaneously and are usually discovered only after a blood clot, a stroke or a heart attack occurs.

“The research that our group has published over the last ten years has had a fairly big impact on how patients are treated, because we try to do studies that deal with a clinical problem,” says Crowther. “So when we designed this study we decided we wanted to help physicians dealing with patients with APLA. The question is – how should these patients be treated? That’s the question we tried to answer.”

As principle investigator, Crowther lead a team of talented colleagues in a comparison of two intensities of warfarin (blood thinner) for the prevention of recurrent thrombosis in APLA patients. They wanted to determine whether high-intensity warfarin therapy is required in patients with antiphospholipid antibodies.

Patients were followed for almost three years in the first randomized trial of the efficacy and safety of high-intensity versus moderate-intensity warfarin therapy in patients with APLA. Because higher-intensity warfarin therapy is associated with a risk of major hemorrhage, it was important to know whether the higher-intensity treatment was more effective.

“For patients who have these antibodies, and who have had previous blood clots, warfarin is the standard treatment. The recommended dose has been to treat with an international normalized ratio (INR) of more than three. In fact, our study was designed to show that you should aim for a target of three to four,” says Crowther. “But to our surprise, we found no evidence that the higher intensity was better.”

The study concluded that high-intensity warfarin therapy is not more effective than moderate-intensity warfarin for the prevention of recurrent thrombosis in patients with APLA. The results also showed that the absolute risk of recurrent thrombosis was low if warfarin therapy was targeted to an INR of 2.0 to 3.0.

Crowther says the publication of this trial is set to have an immediate impact on treatment for patients.

“This is the only randomized, double-blind trial to date that provides us with any guidance on how these people should be treated. So de facto it will establish the treatment standard.”

The Thrombosis Interest Group of Canada – a group of blood clot experts from across Canada who meet regularly and make recommendations on how people should be treated – has already incorporated the study results in their guidelines.

This study was recently published in the New England Journal of Medicine. In a rare event, it was one of two studies published in the same edition of the Journal by two doctors from the same hospital.