The purpose of this study is to compare liberal red blood cell transfusion therapy with
restrictive red blood cell transfusion therapy in surgical patients with cardiovascular
disease or risk factors.
Red blood cell transfusions are an extremely common medical intervention in both the United
States and worldwide; over 14 million units of blood are transfused in the United States.
Between 60 and 70 percent of all blood is transfused in the surgical setting. Despite the
common use of red blood cell transfusions, the threshold for transfusion has not been
adequately evaluated and is very controversial. A decade ago, the standard of care was to
administer a peri-operative transfusion whenever the hemoglobin (Hgb) level fell below 10
g/dl (the "10/30 rule"). Concerns about the safety of blood, especially with respect to HIV
and hepatitis, and the absence of data to support a 10 g/dl threshold led to the current
standard of care, which is to administer blood transfusions based on the presence of
symptoms, and not a specific Hgb/hematocrit level. However, there have not been any
randomized clinical trials done with surgical patients that have tested the efficacy and
safety of withholding blood until the patient develops symptoms, or the "10/30" approach to
transfusion. Patients with underlying cardiovascular disease are at greatest risk of adverse
effects from reduced Hgb levels.
This is a multi-center randomized trial to test the effectiveness of a transfusion strategy
that maintains postoperative Hgb levels above 10 g/dl (liberal transfusion) in improving
patient outcome. This will be compared to the restrictive (symptomatic) transfusion strategy
in which blood transfusion is withheld until the patient develops symptoms of anemia or Hgb
less than 8 g/dL. Participants will be randomly assigned to one of the two transfusion
strategies. The liberal (10 g/dl) threshold strategy will use enough red blood cell units to
maintain Hgb levels at or above 10 g/dl through hospital discharge. Restrictive
(Symptomatic) transfusion strategy patients will receive red blood cell transfusions for
symptoms of anemia, although transfusion is also permitted, but not required, if the Hgb
level falls below 8 g/dl. Outcomes will include functional recovery (primary outcome:
ability to walk 10 feet across a room without human assistance or death 60 days
post-randomization), lower extremity activities of daily living and instrumental activities
of daily living, survival up to 60-days and long-term, disposition (i.e., nursing home
placement), and postoperative complications (e.g., myocardial infarction, unstable angina,
or death in hospital, pneumonia, wound infection, thromboembolism, stroke).
Ambulation at 60 days is known to be highly predictive of ultimate functional outcome as
well as of mortality at one year. Because inability to walk has such important implications
for quality of life, and because it is a common problem, it far outweighs the small risk of
viral infection or other complications from transfusion in elderly patients.
The trial will also evaluate the effect of transfusion threshold on postoperative risk of
acute cardiac ischemia. The strategy will be to enhance surveillance for ischemic events by
increasing the number of EKG and serum troponin measurements beyond those already called for
in the original FOCUS protocol.
There is an ancillary study to the trial (R01 HL085706) to examine delirium as an outcome in
a subsample of 139 patients. We will assess short-term (in hospital) and longer-term (after
30 days) severity of delirium.
- Has undergone surgical repair for a hip fracture
- Has a postoperative Hgb level below 10 g/dL within three days of surgery
- Diagnosis of cardiovascular disease (e.g., coronary artery disease, congestive heart
failure, stroke or transient ischemic attack, or peripheral vascular disease) or
cardiovascular risk factors (e.g., diabetes mellitus, hypertension,
hypercholesterolemia, tobacco use, or creatinine levels greater than 2.0 mg/dL)
- Unable to walk prior to hip fracture
- Declines blood transfusions
- Suffered multiple traumas
- Pathologic fracture of the hip due to malignancy
- Clinically recognized acute myocardial infarction within the 30 days prior to study
- Previously participated in the trial and fractured the other hip
- Symptoms associated with anemia (e.g., ischemic chest pain) or actively bleeding at
the time of randomization