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Red Blood Cell Transfusion

Red blood cells (RBCs) are the cells that remain following separation of plasma from whole blood at any time during storage. RBCs preserved with Adsol contain approximately 30 to 40 mL of CPD plasma, 100 mL of Adsol solution, and 150 – 230 mL of red cells and have a shelf life of 42 days. The hematocrit is 55 to 80%. RBCs produced without Adsol contain approximately 70 mL of CPDA1 plasma, have a hematocrit of 70 to 80% and a shelf life of 35 days.

Treatment of Acute Anemia

Transfusion of RBCs is indicated to increase oxygen delivery in patients who are actively bleeding and in those who have symptomatic anemia unresponsive to specific therapy. The primary therapy for acute hemorrhage is volume replacement with crystalloid, because the treatment of or prevention of hypovolemic shock is more important than restoration of oxygen carrying capacity. If symptoms persist after volume repletion, red cell transfusion should be considered. Symptoms include syncope, pallor, dyspnea, postural hypotension, tachycardia, angina, transient ischemic attacks, and others noted below. The presence of these symptoms indicates that the patient was unable to compensate for the reduced oxygen carrying capacity. The normal compensatory mechanisms include increased cardiac output, peripheral vasoconstriction and increased oxygen extraction by peripheral tissues. These signs and symptoms can be used to estimate the percentage of blood loss


Blood Loss (mL)

% Blood Volume

Signs & Symptoms




1000 - 1500

16 - 20

tachycardia (110-120), exercise tachypnea, postural hypotension

1500 - 2000

20 - 30

tachycardia at rest (120), hypotension (90 mm systolic), sweating, air hunger, anxiety, restlessness



severe hypotension (60 mm systolic)



severe hypotension, pale, cold, ashen, drowsy or unconscious

The loss of 500 mL of blood within 5 minutes is well tolerated by the average adult blood donor.  Therefore, it is usually not necessary to transfuse patients with a single unit of RBCs since the recipient probably needs the blood no more than the donor. Patients who have suddenly lost more than 20 to 30% of their blood volume are more critical and develop symptoms in spite of compensatory mechanisms such as peripheral vasoconstriction and fluid shift from the extravascular to the intravascular space. Hemodilution begins almost immediately after the onset of hemorrhage and continues up to 72 h after cessation of bleeding. Although this influx of fluid does not improve oxygen carrying capacity, it does help to maintain blood volume and stabilize circulation. In this situation, transfusion of a single unit of RBCs along with crystalloid solutions is justifiable since the patient has lost the equivalent of three units of blood. Adult patients in hemorrhagic shock have usually lost 35 to 40% of their blood volume, or approximately 2 liters.

Blood volume should be immediately replaced with crystalloid solutions such as lactated Ringer's solution or normal saline. The early administration of fluids allows sufficient time for ABO typing of the recipient, which takes only a few minutes. In this way, ABO type specific blood can be given instead of empirically giving O negative blood, which often is in short supply.

Transfusion Trigger

Historically, the widely accepted clinical standard was to transfuse patients when the hemoglobin level dropped below 10.0 g/dL or the haematocrit fell below 30%. This ‘10/30 rule’ was first proposed in 1942 and served as the RBC transfusion trigger for decades. In 1988 an NIH Consensus Conference concluded that existing medical evidence did not support a single hemoglobin threshold for transfusion.

Eleven years later, the seminal Transfusion Requirements in Critical Care (TRICC) trial was published, which compared clinical outcomes in intensive care patients randomized to a restrictive versus a liberal transfusion strategy (NEJM 1999;340:409-17). Patients in the restrictive cohort were transfused when their hemoglobin fell below 7 g/dL and their hemoglobin was maintained between 7–9 g/dL, while patients in the liberal transfusion group were transfused when their hemoglobin concentration fell below 10 g/dL and their hemoglobin was maintained between 10–12 g/dL. The TRICC trial demonstrated that a more restrictive transfusion strategy was safe in the ICU patient population and that the liberal use of transfusions increased the risk of death.

TRICC Trial Outcomes







#RBC units



Transfusion avoidance



ICU stay

11.5 days

11.0 days

30 day survival



60 day survival



Recently, two more major studies have confirmed the value of blood conservation.  In 2010, the TRACS trial evaluated a restrictive versus liberal blood transfusion approach to patients undergoing CABG surgery or cardiac valve replacement or repair, alone or in combination (JAMA 2010;304:1559-67). The objective was to determine if a restrictive perioperative red blood cell transfusion strategy targeting a hematocrit of 24% was as safe as a liberal strategy targeting a hematocrit of 30%. Results showed that there was no significant difference in 30 day all-cause mortality and severe morbidity between the two groups. Interestingly, patients who received RBC transfusions had a longer ICU and hospital stay. In addition, the number of transfused RBC units was an independent risk factor for worse outcomes, including mortality.

Today, there is much debate in the medical community as to whether cardiac patients should be maintained at higher hemoglobin levels to avoid cardiac complications. The FOCUS trial was designed to address this issue (N Engl J Med 2011.DOI:10.1056/NEJMoa1012452). In this study, 2016 patients with a history of ischemic heart disease, who were undergoing surgical repair of a fractured hip, were randomly assigned to one of two groups once their postoperative hemoglobin level fell below 10 g/dL. The liberal-strategy group received single unit RBC transfusions to maintain hemoglobin levels above 10 g/dL, while the restrictive- strategy group were transfused at levels below 8 g/dL. The primary outcome (death or inability to walk 10 ft without human assistance) did not significantly differ between the two groups even though the restrictive group received only half the number of transfusions administered to the liberal group. Furthermore, in hospital myocardial events, other coexisting illnesses, and final discharge destination did not differ between the two groups, although this was not the focus of the study.

Recently, a meta-analysis of 19 random controlled trials including 6242 patients was undertaken (Cochrane Database Syst Rev 2012;4: CD002042). Trials included surgical, medical and critical care patients in several different clinical settings including cardiac surgery, orthopedic surgery, vascular surgery, acute blood loss/trauma, cancer and critical care. There was considerable variation with regard to the restrictive and liberal transfusion strategies used in these studies. In general, restrictive strategies maintained hemoglobin between 7.0 and 9.0 g/dL, while liberal strategies maintained hemoglobin levels at or above 9.5, 10.0 or 12.0 g/dL.

As expected, a restrictive transfusion trigger reduced the risk of exposure to RBC transfusion and the total number of units transfused. Restrictive transfusion strategies reduced the absolute risk of a patient being transfused by 34% and the number of RBC units transfused per patient by an average by 1.19 (95% CI 0.53 to 1.85 units). The average hemoglobin level of patients in the restrictive cohort was 1.5 g/dL lower than patients in the liberal cohort.

This meta-analysis confirmed the most important outcomes of the TRICC trial. Restrictive transfusion strategies were associated with a statistically significant reduction in hospital mortality (RR 0.77, 95% CI 0.62 to 0.95) but not 30-day mortality (RR 0.85, 95% CI 0.70 to 1.03). Restrictive transfusion strategies did not adversely affect mortality, cardiac morbidity, stroke, wound healing, mental confusion, functional recovery, length of hospital or ICU stay. In contrast, the evidence suggested that liberal transfusion strategies increase in-hospital mortality by 23% and infection by 19%.

This meta-analysis supports the move to restrictive transfusion practice in most patients, including those with pre-existing cardiovascular disease. Trials in adult and pediatric intensive care unit patients confirm the safety of a 7.0 g/dL threshold in patients with severe acute illness. It is important to realize that no trials have studied the effects of restrictive transfusion triggers in patients with acute coronary syndrome.

Transfusion medicine has evolved over the last few years. Because allogeneic transfusions are a potential risk for patients, physicians should attempt to limit transfusions by aggressively preventing anemia in hospitalized patients. The decision to transfuse RBCs should be based on the entire clinical picture and not solely on the hemoglobin level. Blood Conservation utilizes a comprehensive multidisciplinary approach encompassing pharmaceutical therapy, technology, and blood conservation strategies to conserve patients’ own blood and to enhance blood cell production. Patients benefit from this approach with earlier identification and treatment of anemia as well as the reduced need for a blood transfusion.

Reversible causes of chronic anemia such as vitamin B12, folate, and iron deficiency should be ruled out prior to transfusion. Erythropoietin sensitive anemia such as anemia of chronic renal insufficiency and the anemia associated with zidovudine (AZT) treatment of HIV patients should also be ruled out. Red cell transfusions may be required to alleviate the symptoms of anemia or to reduce morbidity associated with a patient’s underlying disease. Symptoms in normovolemic patients that may indicate the need for transfusion include dyspnea, syncope, transient ischemic attacks, postural hypotension, tachycardia, tachypnea, and angina.

Chronic anemia patients undergo compensatory changes that acclimate them to lower hemoglobin levels. A point of fundamental importance is that blood volume is decreased only slightly in patients with chronic anemia due to compensatory increases in plasma volume. Thus, transfusion of chronically anemic patients may cause hypervolemia which has the potential for precipitating cardiac decompensation, particularly in elderly patients or in patients with known heart failure.

Physicians must not be overly aggressive in the transfusion of patients with severe anemia. Transfusion will improve functional status in symptomatic patients up to a hemoglobin level of 10 g/dL. Transfusions beyond this level provide no further improvement in functional status in most patients. This is especially true for patients with impaired cardiac output because their inability to compensate for increased blood viscosity can actually decrease tissue oxygenation. The major exception is patients with severe chronic obstructive pulmonary disease (COPD) who may still be symptomatic at hemoglobin levels of 10 g/dL and require a hemoglobin level between 10 and 12g/dL to alleviate symptoms. Patients taking medications, such as beta-blockers, may not be able to mount an adequate sympathetic response to blood loss. Transfusion to a hemoglobin level of 10 g/dL may be necessary to relieve symptoms.

Transfusion in the Setting of Angina

Angina may be indicative of an impending myocardial infarction. Indications for transfusion of patients with myocardial infarction are unclear. Transfusion may improve myocardial oxygen delivery, but may also increase myocardial oxygen consumption secondary to increased blood volume and blood viscosity. The decision to transfuse should be based on critical patient evaluation and internal hemodynamic pressure monitoring. Hemoglobin of 8 g/dL is usually tolerable in surgical patients without risk factors for ischemia, while hemoglobin of 10 g/dL may be better for patients with increased risk. Perioperative myocardial infarction is more likely when the hemoglobin is <9 g/dL, especially if the patient has tachycardia.

Perioperative Transfusion

Red cell transfusion has often been used empirically prior to general anesthesia when the hemoglobin is less than 9 or 10 g/dL. There are no data that strongly support this practice. Rather than use a formula approach, proper preoperative assessment should correlate the adequacy of the hemoglobin level with the cause and duration of the anemia, the patient's cardiac and pulmonary status and the type and probable duration of the surgery. The key to tolerance of anemia is the maintenance of normovolemia and compensatory mechanisms that increase cardiac output and improve oxygen transport. Each patient should be evaluated based upon the anticipated ability of his/ her cardiovascular system to compensate.

Hemodynamic instability may also occur during acute blood loss, usually after loss of 15% or more of blood volume. Accordingly, red cell transfusion is indicated if acute blood loss causes the blood pressure to drop by 20% or to a level of <100 mm Hg, or if the pulse increases to >100/min. The transfusion of colloid and/or crystalloid solutions is also necessary in bleeding patients to maintain adequate blood volume. As long as normovolemia is maintained with colloid and/or crystalloid solutions and the patient's hemoglobin level is adequate, it is not necessary to replace all losses of red cells. Fresh frozen plasma should not be used for volume replacement since this incurs the unnecessary risk of infectious disease transmission.

Postoperative hemoglobin in the range of 8-9 g/dL appears to be safe for patients free of cardiovascular disease, and justification should be provided if blood is transfused other than to replace losses at this level. On the other hand, compensation for acute anemia requires increased cardiovascular performance. Moderate hemodilution (below a hemoglobin of 8-10 g/dL) does affect cardiac workload, and its risks should be weighed carefully in patients with extensive cardiovascular disease.

Each unit increases an adult's (70kg) hemoglobin 1g/dL and hematocrit 3%. Follow up measurement of the recipient's hemoglobin and/or hematocrit can be performed between 15 minutes and 24 hours post-transfusion. The optimal time interval for assessment is 15 minutes. Hemoglobin levels obtained at 24 hours post-transfusion are 10% higher than values obtained after 15 minutes.


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