(right to left) Jeffrey L. Carson, MD, Richard C. Reynolds professor of medicine, chief, division of general internal medicine, UMDNJ-Robert Wood Johnson Medical School, Helaine Noveck, MPH, deputy director, clinical coordinating center, FOCUS clinical trial

When should patients receive blood transfusion? by Jeffrey L. Carson

More than 11 million units of blood are transfused each year in the U.S. Between 60% and 70% of blood transfusions are given to patients undergoing surgery, with the majority of blood transfusions given to older patients. Despite the common use of red blood cell transfusions, physicians are not sure how much blood people need after surgery. This study is being conducted to determine when blood transfusions should be given to patients after surgery for a broken hip. The purpose of this study is to compare two plans for giving blood transfusions to patients. Some physicians give a blood transfusion to keep the blood concentration at about 10 grams, whereas other doctors wait until the blood count is less than 8 grams before giving a transfusion. Healthy people have blood counts above 12 grams. Doctors are unsure how much blood patients need for optimal recovery after surgery. With more knowledge and understanding of how blood transfusions improve recovery from surgery, we hope to provide a more effective and timely treatment so that a greater number of patients can recuperate appropriately.

Despite the enormous number of red blood cell transfusions in the U.S, we have very little high quality scientific data to guide us as to when blood should be administered. Most of the efforts during the past 20 years have been directed at improving the safety of blood transfusions. Back in the 1980s the risks from blood transfusions were high, since HIV had contaminated the blood supply. New screening procedures and tests, such as nucleic acid testing for HIV and hepatitis C, have greatly reduced the risk of transmission of viral diseases. The current risk of acquiring HIV or hepatitis C is now only one in two million. New risks, such as West Nile virus and variant Creutzfeldt-Jacob disease, are extremely rare. Overall, the risks related to blood transfusion appear to be very low.

What is needed is new information to serve as a guide for when blood should be transfused. Most research on the indications for blood transfusion is flawed and potentially biased. Only one adequately powered clinical trial has been performed in intensive care unit patients. This trial found that patients receiving a restrictive transfusion approach (7 g/dL trigger) do as well as patients receiving a liberal transfusion approach (10 g/dL trigger). However, it is unknown if these results generalize to surgical patients. Furthermore, we have previously demonstrated in an NIH-funded study of nearly 2,000 patients who declined blood for religious reasons that the odds of death in patients with underlying cardiovascular disease is greater than for patients without cardiovascular disease. This is due to a decline of the preoperative hemoglobin in patients with cardiovascular disease. Thus, it is unclear if it is safe to withhold transfusion in patients with underlying cardiovascular disease.

With this knowledge in mind, the National Heart, Lung, and Blood Institute has funded a new clinical trial called Transfusion Trigger Trial for Functional Outcomes in Cardiovascular Patients Undergoing Surgical Hip Fracture Repair (FOCUS). This study is a randomized clinical trial 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.  In the study, 2,600 patients from 25 medical centers in the U.S. and Canada who undergo
surgery for hip fracture, have a history of cardiovascular disease, and have a postoperative hemoglobin level less than 10 g/dL within three days of surgery, are eligible.  Patients will be randomized to receive enough blood to raise the hemoglobin level above 10 g/dL. If at any time the hemoglobin level is detected to be below 10 g/dL during the hospitalization or if symptoms of anemia develop, the patient will receive a transfusion.  Transfusion is permitted but not required if the hemoglobin level is less than 8 g/dL.  The primary outcome is the ability to walk 10 feet (or across a room) without human assistance at 60 days.  The most important negative outcome is postoperative unstable angina, myocardial infarction or death. Myocardial infarction will be diagnosed based on four blood specimens, three electrocardiograms, and a medical history. Medical records will be reviewed while the patient is in the hospital.  Patients will be telephoned at 30 and 60 days after entry into the study to determine functional capacity and vital status.  Long-term mortality will be determined by searching vital statistics registries in the U.S. and Canada.

The results of this trial should have a profound impact on the use of blood transfusions in patients with cardiovascular disease. If the FOCUS trial demonstrates that higher blood counts improve functional recovery, or reduce the risk of postoperative complications such as myocardial infarction, then clinicians will have a compelling reason to use a liberal transfusion strategy. On the other hand, if the 10 g/dL strategy does not have greater efficacy in this highly sensitive population of patients with cardiovascular disease, then the question of transfusing to greater than 8 g/dL will be closed. The results of FOCUS should be available in about four years.

Jeffrey L. Carson, MD, is the Richard C. Reynolds Professor of Medicine and chief of the division of general internal medicine. He is the principal investigator and study chair of the FOCUS clinical trial at RWJMS. Dr. Carson completed a fellowship in epidemiology and biostatistics at the University of Pennsylvania and was a resident and chief resident at Hahnemann Medical College, also in Pennsylvania. He is a board-certified internist and his practice includes the care of pre- and postoperative surgical patients. His research in blood transfusions began more than 17 years ago with the initiation of a cohort study involving Jehovah’s Witness patients. Dr. Carson has published more than 125 peer reviewed papers, book chapters, and editorials. He has been awarded five teaching awards, including the 2002 Alpha Omega Alpha Faculty Recognition Award.§