Triggering Change in Transfusion Medicine
words by susan glick /
photograph by pete byron
istorically, blood has been synonymous with life. Evidence of attempted transfusions reaches back to a 15th century pope who was given the blood of younger men in an attempt to revive him from a coma. For centuries since, little doubt has existed that transfusions can be life sustaining. Modern medicine has proven that blood transfusions generally work.
But, as Jeffrey Carson, MD, believes, “generally” is not good enough. Thirteen years ago, Carson knew it was time to find out just how accurate the accepted approach is to initiating transfusions, which are not always successful, and can, in fact, be harmful. Unfortunately, transfusion practice lacked tangible medical research. “Some physicians give a blood transfusion to keep the hemoglobin concentration at about 10 grams per deciliter (g/dL), whereas other doctors wait until the blood count is less than 7-8 g/dL before giving a transfusion,” says Carson. “Healthy people have hemoglobin counts above 12 g/dL. Doctors are unsure how much blood a patient needs for optimal recovery after surgery.” Carson saw a strong need to establish clinically proven guidelines for transfusion.
Thus in 1996, Carson wrote the first draft of his clinical research proposal on transfusion triggers as an NIH/ Senior International Fogarty Scholarship recipient in England at Oxford. Today, he is bringing to conclusion the largest randomized clinical trial in red blood cell transfusion, entitled “FOCUS, Transfusion Trigger Trial for Functional Outcomes in Cardiovascular Patients Undergoing Surgical Hip Fracture Repair.” Previously, the largest such trial enrolled 824 patients. FOCUS, funded by the National Heart, Lung, and Blood Institute (NHLBI), has enrolled more than 2,000.
FOCUS was designed to test the hypothesis that a higher blood transfusion threshold improves functional recovery and reduces morbidity and mortality in patients with underlying cardiovascular disease (CVD). “For years, the general consensus was that patients with CVD need more transfused blood than those without CVD, but there was no evidence to back this up,” says Carson. Due to CVD, blocked blood vessels reduce the number of red cells delivering oxygen to the heart; thus, the heart may be more susceptible to anemia. “We are evaluating if those with CVD or CVD risk factors should be given transfusions earlier,” he explains. Though FOCUS is based on hip surgery in the elderly, it is a model for transfusion in any setting.
The primary aim of the study is to see if a transfusion provided when the patient’s count is less than 10 g/dL, not 8 g/dL, improves a patient’s ability to walk 10 feet, or across a room, at 30 and 60 days past surgery. Among the study’s secondary aims is determining if the specified transfusion triggers improve morbidity and mortality, such as lower risk of heart attack, infections, and post-operative nursing home placement.
How do you manage a study with 2,000 patients at 47 hospitals across the U.S. and Canada? Carson, the principal investigator and study chairman, says his primary duty, besides being available 24/7 throughout the duration of the grant, is to maintain relationships with participating institutions and their orthopedic surgeons. He, along with his staff, ensure they follow trial protocol and sustain patient recruitment. “I have contacted each and every one personally at least once to thank them.” Research staff at the hospitals send the patient data to the Data Coordinating Center, run by Michael Terrin, MD, professor of epidemiology and preventive medicine at the University of Maryland.
The Data Coordinating Center ensures the data is reliable, consistent and valid. By study design, Carson and his team are blinded to any interim results. “I have no idea where the data may be pointing.”
What happens to all this data? My expectation is that the results will serve as the basis for transfusion guidelines in patients with CVD. Carson and his team will present preliminary results at an investigator meeting this June in Princeton. Their efforts to analyze the data will continue through the fall and he expects to present final results at several national meetings.
Could this be a landmark study? Even the principal investigator is not sure, though the potential exists. One thing is sure: This massive effort has certainly required blood, sweat and years.