The number of components transfused in the United States was approximately 24 million units in 2008 (2). As the donor pool continues to decrease, there are real concerns that in the near future, demand will exceed supply. Blood use is suboptimal in many hospitals because of poor training and inadequate oversight, review, and monitoring of transfusion practices. Furthermore, there is wide variability in transfusion practices among hospitals, and among individual physicians within the same hospital (1,3,4,5).

The decision to transfuse is often clouded by myths, misconceptions, and emotions, and is frequently not supported by good medical science (6). There is a generalized lack of compliance with appropriate transfusion guidelines at many hospitals.

Although the blood supply is the safest it has ever been (particularly as it relates to the transmission of blood-borne infections), transfusion of blood components remains a high-risk procedure that results in some harm to all patients. The benefits of blood transfusion, especially the use of red cells, are not well elucidated. Few, if any, well-controlled studies demonstrate improved outcomes with red cells. There are a growing number of randomized trials in high-risk patients that show a conservative approach to red cell transfusions is at least as effective as a more liberal strategy. The landmark Transfusion Requirements in Critical Care (TRICC) trial published in 1999 involved a prospective randomized trial of transfusion strategies in 838 ICU patients. The authors’ conclusion was that a restrictive strategy of red cell transfusions (Hgb 7.0) was at least as effective and possibly superior to a more liberal strategy (Hgb 10.0) with the possible exception of those patients with acute coronary syndromes (ACSs) (7). There are now prospective randomized trials showing similar outcomes in critically ill neonatal and pediatric patients (8,9), cardiac surgery patients (10), and there is observational data that suggests that even patients with ACS may not benefit from liberal transfusion strategies (11,12,13). Of great interest to orthopedists is a prospective trial of transfusion strategies in 2,016 elderly patients with cardiovascular disease undergoing hip fracture repair, known as the functional outcomes in cardiovascular patients undergoing surgical hip fracture repair (FOCUS) trial. Patients were randomly assigned to a liberal transfusion strategy (Hgb 10.0) or a restrictive transfusion strategy (Hgb <8.0 or symptoms of anemia), and the primary outcome was death or an inability to walk across a room without assistance on 60-day follow-up. The result showed no difference in complication rates or functional recovery between the two groups, and patients in the restrictive-strategy group received 65% fewer units of blood than those in the liberal-strategy group with more than half not receiving any blood products (14). A recently published clinical practice guideline from the AABB reviewed 19 randomized controlled studies of red blood cell therapy that included a total of 6,242 patients. The guideline endorsed a restrictive transfusion strategy (7 to 8 g/dL) in hospitalized, stable patient and also suggested adhering to a restrictive strategy in patients with pre-existing cardiovascular disease with symptoms or a hemoglobin level of 8 g/dL or less (15).

As with any medical therapy, the decision to transfuse must be made in the context of an informed risk and benefit analysis. In addition to the decreased efficacy of transfusions noted from these randomized trials, there is evolving evidence that shows the risks of transfusion have also been underestimated. While most transmissible risks of blood have been greatly reduced, bacterial contamination of platelets occurs with a frequency of 1:2,000 to 3,000 transfusions (16). The most significant concern for transfusion therapy are now the noninfectious serious hazards of transfusion (17). Transfusion of blood products to the wrong
patient is a leading risk with the alarming frequency of 1:12,000 to 19,000 units transfused, with death occurring in 1:600,000 to 800,000 transfusions (18). One of many concerns about autologous predonation is that the likeliness of any transfusion event is increased 3- to 12-fold in patients who predonate, increasing the risk of clerical error (19). Transfusion-associated circulatory overload (TACO) is perhaps the most frequent transfusion-related complication that results in significant morbidity, and the frequency may be as high as 6% to 8% in critically ill and orthopedic patients (20,21). TACO is exacerbated by both physician ordering habits that encourage two unit transfusions, and by nursing staff who often transfuse susceptible patients too rapidly. Transfusion-related acute lung injury (TRALI) is the leading cause of transfusion-related mortality and occurs with a frequency of 1:5,000 to 100,000 transfusions (22). Like TACO, its occurrence is likely underreported because of a lack of awareness by clinicians. TRALI can be caused by the presence of anti-HLA antibodies in donor plasma that attack recipient white cells, predominantly in female donors with multiple previous pregnancies. In the past several years, most countries have eliminated or reduced the number of female plasma donors with a resultant decrease in TRALI cases. There is also a second mechanism for TRALI related to inflammatory mediators in stored blood that will be discussed below. Transfusion-related immunomodulation (TRIM) is of great concern because it leads to increased rates of hospital-acquired infections in surgical and medical patients. While the etiology is likely multifactorial, the immune challenge presented by the antigenic load of allogeneic transfusions as well as soluble mediators in stored blood are prime suspects (23,24). This TRIM effect is thought to be contributory to the consistent finding of dose-dependent increases in infection rates, ventilator support times, ICU and hospital length of stay, short-term and long-term mortality, and cancer recurrence rates in transfused patients (25,26).

Many physicians find it counterintuitive that red cell transfusions cause this wide range of adverse outcomes in patients. However, insight into the pathophysiologic basis for these adverse effects can be obtained by an understanding of what occurs to red blood cells during their storage cycle, the so-called “storage lesion.” Prolonged storage of blood products (both allogeneic and autologous) leads to a progressive decline in red cell quality (decreases in 2,3-DPG, ATP, and nitric oxide levels, alterations in red cell morphology and rheology) and a progressive accumulation of harmful debris (cell membrane microparticles, plasma free Hgb, K⁺

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