Clinical Transfusion

5. Red cell transfusion triggers

A large variation in transfusion policy between countries and even between hospitals within a country can still be seen as common practice:

  • In the first Austrian benchmark study, Gombotz and colleagues found a transfusion rate varying from 16 to 85% for patients undergoing primary total hip replacement (THR) and a 12-87% transfusion rate for patients undergoing primary total knee replacement (TKR) surgery (Gombotz et al. Transfusion 2007). 
  • In the second benchmark study, which was published recently, transfusion rates have decreased in THR (from 41 to 30%) and TKR (41 to 25%) however with still substantial inter-centre variability (Gombotz et al. Transfusion 2014) These studies show, that the implementation of guidelines in daily practice is often difficult. This is not only relevant for implementing transfusion thresholds, but also for the number of transfusions at each event to reach a particular target Haemoglobin (Hb) level. 

Barr and co-workers investigated red blood cell transfusion practice in Northern Ireland in 2005 and still found a two-unit instead of single-unit transfusion practice in medical and surgery patients (n=1474) (Barr et al. Vox Sang 2010).

Scientific evidence to support restrictive transfusion thresholds

Key messages:

  • Use of a restrictive blood transfusion protocol can be regarded as an important blood saving and cost-saving strategy.

  • Restrictive transfusion does not lead to adverse events when compared to liberal transfusion strategies in the non-high risk patient (regarding mortality, cardiac events, myocardial infarction, stroke, pneumonia and thromboembolism).

  • Effects of restrictive transfusion triggers in high risk groups such as acute coronary syndrome need to be tested in further large clinical trials.

In 1988 the NIH published consensus guidelines for red blood cell transfusions. Since then, several guidelines have been published, recommending that a range of Hb levels between 6 and 10 g/dL can be used, depending on the presence of serious co-morbidity:

Randomized studies comparing liberal to restrictive transfusion triggers

These clinical practice guidelines, however, have based their recommendations on data from published reports on series of patients for whom red cell transfusions were withheld (for instance Jehovah’s witnesses), and observational studies, rather than on the results of clinical trials. However, since then many randomized studies were published comparing a liberal to a restrictive transfusion trigger.

A systematic review from Carson and coworkers  (Carson, Carless, Hebert, Cochrane Database Syst. Rev. 2012) showed that restrictive transfusion strategies reduced the risk of receiving a RBC transfusion by 39% (RR 0.61, 95% CI 0.52 to 0.72). This equates to an average absolute risk reduction (ARR) of 34% (95% CI 24% to 45%). The volume of RBCs transfused was reduced on average by 1.19 units (95% CI 0.53 to 1.85 units). However, heterogeneity between trials was statistically significant (P<0.00001; I(2)>93%) for these outcomes. Restrictive transfusion strategies were associated with a statistically significant reduction in hospital mortality (RR 0.77, 95% CI 0.62-0.95) but not 30 day mortality (RR 0.85, 95% CI 0.70 to 1.03). The use of restrictive transfusion strategies did not reduce functional recovery, hospital or intensive care length of stay. The majority of randomized patients were included in good quality trials, but some items of methodological quality were unclear. There are no trials in patients with acute coronary syndrome. The authors concluded that the existing evidence supports the use of restrictive transfusion triggers in the majority of patients, included patients with a cardiovascular history (Carson et al, Transfusion 2006).

A more recent meta-analysis including 31 randomized trials (n=9813) again concluded that a restrictive transfusion trigger reduced transfusion rate (RR 0,54, 95% CI 0,47 to 0,63)  and the number of transfused RBC units (1,43 units, 95% CI 0,86 to 2,01 units) without  any difference in overall mortality and overall morbidity (Holst et al. BMJ 2015).

Another systematic review focussed on the effect of transfusion thresholds on postoperative infection rate and concluded that using restrictive transfusion thresholds lowered infection risk (Holst et al. New Eng J Med 2014).

However, additional evidence regarding a  randomized trial among cardiac surgery patients found no differences in infection rate and other postoperative complications between the liberal and restrictive groups, however more patients died after 90 days in the restrictive group (OR 1.64 95% CI 1.00 to 2.67; p=0.045) (Murphy et al. New Eng J Med 2015). 

A study of interest was published by Villanueva and coworkers. These authors concluded that a restrictive transfusion strategy significantly improved outcome in patients with acute upper gastrointestinal bleeding (Villanueva et al. New Eng J Med 2013).

  1. Consensus conference. Perioperative red blood cell transfusion . JAMA 1988; 260: 2700-03.
  2. Consensus statement on red cell transfusion. Royal College of Physicians of Edinburgh . Transfus. Med. 1994; 4: 177-78.
  3. Practice Guidelines for blood component therapy: A report by the American Society of Anesthesiologists Task Force on Blood Component Therapy . Anesthesiology 1996; 84: 732-47.
  4. Practice guidelines for perioperative blood transfusion and adjuvant therapies: an updated report by the American Society of Anesthesiologists Task Force on Perioperative Blood Transfusion and Adjuvant Therapies . Anesthesiology 2006; 105: 198-208.
  5. The epidemiology of red cell transfusion. Barr PJ et al. Vox Sang 2010; 99: 239-50.
  6. Transfusion thresholds and other strategies for guiding allogeneic red blood cell transfusion. Carson JL, Carless PA, and Hebert PC. Cochrane. Database. Syst. Rev. 2012; 4: CD002042.
  7. Transfusion trigger trial for functional outcomes in cardiovascular patients undergoing surgical hip fracture repair (FOCUS). Carson JL et al. Transfusion 2006;46: 2192-206.
  8. Blood use in elective surgery: the Austrian benchmark study. Gombotz H et al. Transfusion 2007; 47: 1468-80.
  9. The second Austrian benchmark study for blood use in elective surgery: results and practice change. Gombotz H et al. Transfusion 2014; 54; Pt 2: 2646-57.
  10. Lower versus higher hemoglobin threshold for transfusion in septic shock. Holst LB et al. NEJM 2014; 371: 1381-91.
  11. Restrictive versus liberal transfusion strategy for red blood cell transfusion: systematic review of randomised trials with meta-analysis and trial sequential analysis. Holst LB et al. BMJ 2015; 350: h1354.
  12. Liberal or restrictive transfusion after cardiac surgery. Murphy GJ et al. NEJM 2015; 372: 997-1008.
  13. Transfusion strategies for acute upper gastrointestinal bleeding. Villanueva C et al. NEJM 2013; 368: 11-21.
Cynthia So-Osman

Cynthia So-Osman


The Netherlands


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