TMU SPECIAL EDITION: THE TRANSFUSION TRIGGER UPDATED:
CURRENT INDICATIONS FOR RED CELL THERAPY
Vol. 6, No. 2,
Recent studies have called into question the
traditional concept of the transfusion trigger. Until the mid-1980s, this
value, defined as the hemoglobin or hematocrit laboratory level at which most
patients need red blood cell transfusion, was approximately 10/30; most medical
or surgical patients were transfused at that level. During the past 15 to 20
years, a number of studies suggested that otherwise “healthy” adults could
tolerate a greater degree of anemia without compromise. A number of transfusion
guidelines published in the late 1990’s have been summarized and were reviewed
in Blood Bulletin (Vol. 2, #3 1999).
Clinical transfusion therapy relies on clinical experience and investigation.
The most highly regarded investigative studies are randomized clinical trials of
various transfusion triggers; observational studies are also valuable. Both are
reviewed in this issue of Blood Bulletin.
Observational studies. Several studies have been
conducted involving Jehovah’s witnesses who have undergone surgery and refused
transfusion for religious reasons. An analysis of approximately 2000 adult
patients undergoing surgery, excluding open heart procedures, in 12 hospitals
between 1981 and 1994 demonstrated increasing risks as the hemoglobin falls.1
A separate analysis of 300 patients with postoperative hemoglobin of 8.0g/dL or
below was performed.2 The subset included 70% females, with a mean
age of 57 years. The overall mortality rate was 16%. Those with postoperative
hemoglobin levels of 7.1-8g/dL had no deaths (upper 95% CI 3.7%), but 9.4% (CI
4.4-17%) had a morbid event, defined as a myocardial infarction, congestive
heart failure, arrhythmia, or infection (bacteremia, pneumonia, or deep wound)
that occurred within 30 days of surgery. Patients with a postoperative
hemoglobin of 4.1 to 5g/dL had a mortality rate of 34.4% (CI 18.6-53.2%), and
57.7 % (CI 36.9-76.6%) had a morbid event. Adjustment for age, cardiovascular
disease, and Acute Physiology and Chronic Health Evaluation II (APACHE II) score
showed that for those with postoperative hemoglobin <8g/dL, every gram decrease
in hemoglobin resulted in a 2.5 times higher risk of death (CI 1.9-3.2).
patients with cardiovascular disease (defined as the preoperative presence of
angina, congestive heart failure, or atherosclerosis) had a higher risk of death
with low preoperative hemoglobin, or a decline of hemoglobin level during
surgery.1 These studies quantify the increased risk associated with
cardiovascular disease regarding tolerance of anemia, but do not provide
guidance about a transfusion trigger, since these patients did not receive
Prescribing red blood cell transfusions requires
clinical decision making.
lower limit or "transfusion trigger" for general medical and surgical
patients approximates hemoglobin/hematocrit levels of 7.0g/dL and 21%,
respectively. Below these levels, morbidity and mortality increase.
patient subsets, such as elderly patients suffering from acute myocardial
infarction, appear to have better outcomes when transfusions increase the
hematocrit to 30 to 33%.
Current data suggest that restraining
transfusions favors positive patient outcomes—except when significant
underlying cardiac disease is present.
Ten controlled trials conducted over 40 years and involving 1780 patients were
included in a review of randomized clinical trials involving transfusion.3
Outcomes measured included proportion of patients transfused, volume of blood
transfused, morbidity, mortality, and length of hospital stay. Five studies
involved surgical patients, three addressed trauma patients or other acute blood
loss situations, and two were performed in ICU patients.
use of a restrictive transfusion trigger overall (a lower hemoglobin/hematocrit
concentration, although defined differently in the various studies) reduced the
probability of transfusion by 42%, and resulted in an average saving of nearly 1
unit (0.93) per transfused patient. There was no increase in cardiac events,
including infarction, or in the hospital length of stay. Mortality was lower
with the restrictive strategy, though this was not statistically significant
overall. Importantly, no functional status measurements were used. However,
most of the data on clinical outcomes were generated by a single trial.4.
Several other studies stated that restrictive strategies might not be
appropriate for several subsets of patients, including those with significant
Patients with cardiovascular disease. An analysis of the 357 patients
in the above study who had cardiovascular disease showed similar 30-day and
other mortality rates in the two groups.5 In the restrictive group,
those with severe ischemic heart disease had higher (but statistically
insignificant) mortality. The authors assert that the trigger of 7g/dL is as
appropriate in cardiac patients as in other patients. A separate analysis
showed that hemoglobin concentrates and transfusion did not affect the duration
of mechanical ventilation in patients requiring this intervention.6
these reports showed no difference in outcomes between the restrictive and
liberal strategies (or possible benefit of restricting transfusion in some
subsets), a large multicenter observational study of European ICU’s8 showed 33% higher mortality
among transfused patients versus non-transfused patients—even when all
other variables were controlled, including scores of acuity and organ
dysfunction. However, these results should be interpreted with caution because
of the heterogeneity of the patient population.
certain patient populations, higher transfusion triggers may lead to improved
outcomes. An analysis of nearly 79,000 Medicare beneficiaries with acute
myocardial infarction showed that transfusion was associated a lower short-term
mortality rate if the hematocrit at admission was 30% or lower and transfusion
might be effective in patients with a hematocrit as high as 33%.8
another study of 32 patients with low-level anemia (hemoglobin 10-11.5g/dL)
randomized to treatment with erythropoietin (epo) or placebo, the group
receiving epo had less mortality and strikingly better functional outcomes than
the group not treated.9 This small study and the large observational study by
Wu8 identified patients benefiting from higher hemoglobin concentrations.9 In a
third study, anemia increased the risk of 1-year mortality with acute MI,
although confounding factors such as demographics and co-morbid conditions may
have explained the effect.10 Thus, it appears that a subset of cardiac patients
will benefit from more liberal transfusion—while general surgical and medical
patients may benefit from a more restrictive strategy.
might be the cause of poorer outcomes of transfusion in patients without
cardiovascular disease? One study cites immunomodulation, but gives no specific
examples.6 This and another study suggest that leukocyte content and
the age of red cells transfused may influence outcomes.6, 11
However, a recent study of 1200 ICU patients
showed that mortality was similar in patients receiving epo or
transfusion, at a trigger of approximately 8.5g/dL,12 casting doubt
on the potential role of leukocytes or red cell age. If one assumes excess
mortality in the transfused group, as suggested by the Hebert and Vincent
studies, this effect is not ameliorated by epo.13
Clearly, randomized controlled trials and observational studies have provided
additional data for making clinical decisions. Results of further studies will
provide additional information to enhance the clinical use of blood transfusion.
et al. Effect of anaemia and cardiovascular disease on surgical
mortality and morbidity. Lancet
Carson JL et al. Mortality and
morbidity in patients with very low postoperative Hb levels who decline blood
transfusion. Transfusion 2002;42:812-8.
JL Carson et al. Transfusion triggers: a systematic review of
the literature, Trans Med Rev 2002;16:187-99.
Hébert PC et al. A multicenter,
randomized, controlled clinical trial of transfusion requirements in critical
care. Transfusion Requirements in Critical Care Investigators, Canadian
Critical Care Trials Group. N Engl J Med 1999:340:409-17.
et al. Is a low transfusion threshold safe in critically ill
patients with cardiovascular diseases? Crit Care Med 2001;29:227-34.
Hébert PC et al. Do blood transfusions
improve outcomes related to mechanical ventilation?
Chest 2001;119 :1850-7.
Vincent JL et al. Anemia and blood
transfusion in critically ill patients.
et al. Blood transfusion in elderly patients with acute myocardial
infarction. N Engl J Med 2001;345:1230-6.
Silverberg DS et al. The effect of correction of mild anemia in
severe, resistant congestive heart failure using subcutaneous erythropoietin
and intravenous iron: a randomized controlled study. J Am Coll Cardiol
Al Falluji N et al. Effect of anemia on
1-year mortality in patients with acute myocardial infarction. Am Heart J
Hébert PC and Fergusson DA. Red blood cell transfusions in critically
ill patients. JAMA 2002;288:1525-6.
et al. Efficacy of recombinant human erythropoietin in
critically ill patients: a randomized controlled trial.
Should patients in
intensive care units receive erythropoietin? JAMA 2002;288:2884-6.
©2003, Institute For Transfusion
Editor: Donald L. Kelley, M.D., MBA: