When administering a transfusion of packed red blood cells, it is important to

Packed Red Blood Cells

PRBCs are the most commonly used blood component. PRBCs are prepared from whole blood by centrifugation or by apheresis collection and typically contain less sodium, potassium, ammonia, citrate, hydrogen ions, and antigenic protein than whole blood. This may be beneficial in patients with impaired renal, cardiovascular, or hepatic function. Typically one unit of PRBCs is approximately 350 mL in volume, of which RBC volume is 200 to 250 mL. The remaining volume is due to plasma (typically less than 50 mL), WBCs, platelets, and anticoagulants. The most commonly used anticoagulant is CPDA-1 (citrate, phosphate, dextrose, adenine), which allows for 35 days storage at 1° to 6°C. The hematocrit of such units is less than 80% (range 70% to 80%).

In the United States, most centers provide leukoreduced PRBCs. This is done by leukocyte reduction filters and done before storage. Residual leukocytes should not exceed 5 × 106 per unit. Leukocyte reduced units decrease alloimmunization and reduce chances of febrile nonhemolytic TRs. Leukocyte reduced units are also considered to be cytomegalovirus safe and can be given to cytomegalovirus-negative individuals.

In a nonemergency setting, PRBCs should be transfused at a rate of 1 to 2 mL/min for the first 15 minutes and then increased to 4 mL/min or as rapidly as the patient can tolerate. Transfusion should not exceed 4 hours. Potential life-threatening reactions most commonly occur within the first 15 minutes. In an emergency setting, PRBCs may be transfused at fast rates, and multiple units may need to be transfused. Massive RBC transfusions are defined as >10 units, but with such a transfusion, there is significant risk for metabolic and respiratory acidosis as well as hypocalcemia. Transfusion associated hypothermia and hyperkalemia are also recognized side effects of such a large transfusion.

Each unit of PRBC is expected to increase the hematocrit by 3% and hemoglobin level by 1g/dL. This effect can be measured 15 minutes after transfusion. In a bleeding patient, it must be kept in mind that transfusion of multiple units of PRBC will aggravate the coagulopathic state of the patient.

The unit of PRBC that is being transfused must be compatible with the recipient’s plasma ABO antibodies. Thus if the recipient is blood group A, he/she has anti-B antibodies and cannot be transfused with B or AB units. If the recipient is B, he/she has anti-A antibodies and cannot be transfused with A or AB units. Both A and B patients can receive O units. If the recipient is AB, he/she has no anti-A or anti-B antibodies. Therefore, he/she can receive A, B, AB, or O units. If the recipient is O, he/she has anti-A and anti-B antibodies. He/she can receive only O units.

There are various types of PRBCs that may be made available in special circumstances:

PRBCs leukoreduced: In the United States, most centers provide PRBCs that are leukoreduced. This has decreased the incidence of febrile TRs. Leukoreduced products are also considered to be CMV safe. Leukoreduction also helps to prevent HLA alloimmunization.

pRBCs

pRBCs are manufactured by removal of the majority of plasma from a unit of whole blood. pRBCs have a volume of approximately 250 to 300 mL and a hematocrit of 65% to 80%. pRBCs prepared without further modifications contain white blood cells, platelets, and residual plasma. Transfusion of pRBCs is indicated in the treatment of anemia with symptomatic deficits of oxygen-carrying capacity and hemorrhagic shock when administered with volume expanders. One unit of pRBCs should raise the hemoglobin of an average adult by 1 g/dL and the hematocrit by 3%. For pediatric patients, the usual dose given is 3 mL/kg to raise the hemoglobin by 1 g/dL and the hematocrit by 3%.

Packed Red Blood Cells

PRBCs are prepared by centrifugation and removal of most of the plasma from citrated whole blood. One unit of PRBCs contains the same red cell mass as 1 unit of whole blood at approximately half the volume and twice the hematocrit (55% to 80%) in 250 mL of volume.6 One unit of PRBCs raises the hematocrit approximately 3% in an adult or increases the hemoglobin level of a 70-kg individual by 1 g/dL. In children, there is an approximate rise in hematocrit of 1% for each 1 mL/kg of packed cells. For example, if 5 mL/kg of PRBCs is transfused, the hematocrit will rise by approximately 5%. Actual changes depend on the state of hydration and the rate of bleeding. Because most of the plasma has been removed, PRBCs cause fewer transfusion and allergic reactions than whole blood does.

PRBCs contain less sodium, potassium, ammonia, citrate, hydrogen ions, and antigenic protein than whole blood does. This may offer advantages in patients with reduced cardiovascular, renal, or hepatic function. The rate of urticaria is still relatively high at 1% to 3% of transfusions, but the incidence of adverse reactions to packed cells is approximately one third of that noted with whole blood. The benefit of increased hemoglobin must be weighed against the potential for volume, electrolyte, and acid-base imbalances following PRBC administration. In cases of massive transfusion (>10 units), there is a significant risk for metabolic and respiratory acidosis, as well as hypocalcemia, which can reach life-threatening levels. Although underlying illness or injury obviously plays a major role in the cause of death, the overall mortality of patients requiring massive PRBC transfusions is approximately 60%.7,8

Transfusion of PRBCs is indicated to provide additional oxygen-carrying capacity and expansion of volume. Packed cells are most commonly used to treat acute hemorrhage and anemia that is not amenable to nutritional correction. When treating acute hemorrhage, PRBCs are usually given: (1) if the hemoglobin level falls below established critical levels for that particular given patient population (see the section onTransfusion Thresholds), (2) after rapid crystalloid infusion fails to restore normal vital signs, or (3) concurrently with crystalloid infusion in the treatment of obvious life-threatening blood loss.

Specially prepared or screened types of red cells are listed in the following sections. Their indications for use are presented inBox 28.1.

Packed Red Blood Cells

PRBCs are the cells and the small amount of plasma and anticoagulant that remains after the plasma is removed from 1 unit of whole blood. If 450 mL of blood is collected, the volume of PRBCs obtained is approximately 200 mL. Because the plasma has been removed, the total volume transfused is less than 1 unit of whole blood but contains the same oxygen-carrying capacity as 450 mL of whole blood. In cats, the increase in packed cell volume (PCV) after transfusion of 1 unit of PRBCs has been shown to be equivalent to the increase after transfusion of 1 unit of whole blood.48 PRBCs are used only to treat clinically symptomatic anemia because they do not contain platelets or clotting factors. Red blood cell transfusions are administered to cats for a variety of reasons. Data on 126 cats administered whole blood or PRBCs indicated 52% were transfused for blood loss anemia, 38% for erythropoietic failure, and 10% for hemolytic anemia.48 Similar reasons for transfusion of cats have been reported in Germany.90 Dogs more commonly are transfused for blood loss anemia (70%) with 14% to 22% being transfused for hemolytic anemia and 8% to 14% for erythropoietic failure.8,45 The initial dosage of PRBCs is 6 to 10 mL/kg, and transfusion is continued until the clinical signs of anemia are improved.

Packed Red Blood Cells

PRBCs are indicated only to improve oxygen delivery to tissues at the microvascular level and thus improve intracellular oxygen consumption, yet definitive demonstration of the efficacy of red cells for this purpose (or improved clinical outcomes) has proven elusive.21 A definitive randomized prospective study in which RBCs are withheld completely from one treatment group is unlikely to be done at this point.

I agree with the recommendations published in 2012 by the AABB (formerly, the American Association of Blood Banks), which were based on a systematic review of trials published between 1950 and February 2011. This review found strong support for using a restrictive transfusion strategy (7–to 8 g/dL) for most stable hospitalized patients.22 It was also recommended that transfusion decisions be influenced by symptoms and hemoglobin concentration and specifically addressed the case of hospitalized patients with preexisting cardiovascular disease, suggesting that emergency clinicians consider transfusion for these patients when they had symptoms or a hemoglobin level of 8 g/dL or less. Literature support for these additional recommendations was noted to be weak, however, and no specific recommendations could be made with regard to hospitalized, hemodynamically stable patients with an acute coronary syndrome.22

For many patients, the decision to transfuse RBCs requires clinical judgment. The appropriate trigger for patients with active hemorrhage, for example, is not well established, although a trial in patients with acute gastrointestinal bleeding found somewhat improved survival outcomes overall in patients treated with a restrictive 7-g/dL transfusion trigger.23 I recommend transfusing any patient with ongoing severe hemorrhage and unstable vital signs, despite adequate fluid resuscitation. Conversely I would occasionally consider withholding transfusion for Hgb levels even lower than 6 g/dL in a young, healthy, asymptomatic patient at low risk for further bleeding. Another interesting area of investigation is the use of physiologic transfusion triggers (eg, lactate, mixed venous oxygen saturation), but further research is needed.24

Packed Red Blood Cells

Packed RBCs are made by removing 200–250 ml of plasma from whole blood. The typical volume is 250–300 ml per bag. Each bag will raise the patient's hemoglobin approximately 1 g/dl (hematocrit 3%). Additive solutions are anticoagulant‐preservative solutions that contain varying concentrations of adenine, which allow increased storage of RBCs to a maximum of 42 days. Packed RBCs may undergo further processing for specific indications, including leukocyte reduction, irradiation, or saline washing. The generally accepted threshold for transfusion of packed RBCs has recently been changed from a hemoglobin concentration goal of approximately 10 g/dl to a goal of 7 g/dl because of a recent randomized, prospective study. This hemoglobin concentration goal does not apply to trauma patients. RBCs may be frozen to significantly increase storage time. Glycerol penetrates the RBCs and allows them to freeze without causing damage to the cells. This technique is useful for rare blood types, autologous transfusions, and stockpiling reserves.

15 Discuss the role of acute transfusion in sickle cell disease.

Packed red blood cell transfusions are indicated in the setting of severe anemia with hemodynamic instability, severe hypoxia, or acute end-organ injury. The final hematocrit measurement after transfusion should not exceed a value > 30% because blood viscosity will increase at higher values. In patients with a baseline hematocrit > 30%, transfusion therapy should result in a return to baseline hematocrit level. If life-threatening events such as acute stroke, ACS, or acute multiorgan failure syndrome develop, red blood cell exchange transfusion should be considered, especially if the hematocrit has not fallen significantly below baseline values. An apheresis instrument can be used for an automated exchange procedure using a double-lumen dialysis catheter. Alternatively, aliquots of blood are removed through an arterial or venous line and replaced with whole blood or “reconstituted” packed red blood cells. In all cases, an effort should be made to match transfused units to minor antigens on the patient's red blood cells (i.e., minor antigen match); otherwise, patients with sickle cell disease tend to develop multiple alloantibodies, making future crossmatching difficult.

Packed Red Blood Cell (Red Cell Concentrate) Transfusion

Packed red blood cell (PRBCs) transfusions are used to improve blood oxygen-carrying capacity and restore blood volume. Units are prepared from whole blood by removing most of the plasma (producing an average hematocrit value of 70%). This procedure reduces the transfusion volume and the isoagglutinin load. Each unit usually contains approximately 200 ml of RBCs, 70 ml of plasma, and 100 ml of additive nutrient solution (e.g., citrate [as an anticoagulant], phosphate, dextrose, and ATP). Clinical citrate toxicity (hypocalcemia due to calcium chelation) is rare, occurring only with massive transfusions (e.g., exchange transfusion), and responds to calcium supplements. Prolonged storage produces a leakage of potassium into the plasma, which is usually clinically insignificant. Blood should be infused through a filter (170 to 260 μm) to remove debris caused by storage.1,2

Transfusion is usually given if the symptoms of anemia or blood loss are severe and further delay might result in significant disability or death. Selected indications for transfusion include acute bleeding, high-dose chemotherapy, severe prematurity, sickle cell disease (e.g., splenic sequestration, severe acute chest syndrome), thalassemia major, aplastic anemia, pure red cell aplasia, and severe autoimmune hemolytic anemia (using the most compatible unit).2 Transfusing 10 to 15 ml/kg of PRBCs in a child raises the hemoglobin concentration by 2 to 3 g/dl and the hematocrit by 6% to 9% (Table 132-2).1,5 Transfusion is usually given at 15 ml/kg over 2 to 4 hours. Faster transfusion may be necessary to replace acute blood loss. If the intention is to transfuse small amounts (e.g., in infants), a unit can be divided into several aliquots.

Leukocyte-reduced PRBCs are prepared by passing the unit through a filter that removes 85% to 90% of the white blood cells; the procedure is frequently performed at the time of blood collection. This type of product produces fewer nonhemolytic febrile reactions, which are mediated by antibodies against the donor's white cell antigens as well as by cytokines produced during component storage. This product also produces less alloimmunization and viral (e.g., cytomegalovirus) transmission. It is indicated for patients who need chronic transfusion (e.g., children on chemotherapy or with hemoglobinopathy) or who have prior exposure to blood antigens (e.g., multiparous females).1

Irradiated PRBCs are prepared by exposing the unit to 2500 cGy of radiation. This treatment inactivates the donor's T cells, which reduces the risk of a graft-versus-host reaction in the recipient. This type of product is recommended for immune-compromised patients (e.g., children on chemotherapy).1

Washed PRBCs are prepared by washing red cells with 0.9% NaCl, which removes most of the plasma. This type of product is used for patients who have severe allergic reactions (e.g., cough, wheezing, swollen lips, and urticaria) to transfusion despite antihistamine administration. Immunoglobulin E antibodies against the donor's plasma proteins mediate this adverse reaction. This product is also used for patients with immunoglobulin A (IgA) deficiency who have developed IgA antibodies.2

Leukoreduction, Stored Blood, and Irradiation

Leukoreduced PRBCs should be used in neonates to decrease the spread of infection, and to decrease the possibility of microchimerism,93 the addition of a small amount of foreign genetic material in addition to the host's genetic material. The shelf life of PRBCs can be as long as 42 days, and there does not appear to be a significant difference in red cells transfused before 7 to 10 days compared with red cells transfused after 21 days.94,95 Studies comparing potassium concentrations in blood stored for various periods of time show no significant increase in blood stored longer than 21 days compared with blood stored less than 7 days.95 Many blood banks will also irradiate PRBCs just before neonatal transfusion. Irradiation of RBCs is recommended for fetuses receiving in utero transfusions, for immunocompromised infants, and for infants receiving directed donor blood from a first- or second-degree relative. Irradiation may reduce the rare complication of graft-versus-host disease.

Selection of red cell products

Packed red blood cells (PRBCs) are the product of choice for neonatal transfusions and may be modified in several ways that remove varying proportions of non-RBC components. These modifications are particularly important in neonates because of their increased vulnerability to certain infections, such as cytomegalovirus (CMV), their increased risk of GVHD due to transfusion, and possible alloimmune hemolytic disease of the newborn. Leukoreduction decreases the chance of alloimmunization and reduces the transmission of certain infections, including CMV. CMV-negative PRBCs also reduce CMV transmission and are most helpful in infants born to CMV-seronegative mothers. Irradiation does not provide a CMV-safe product but may decrease transfusion-associated GVHD. Washing PRBCs before transfusion removes remnant plasma that may contain antibodies directed against the infant’s own red cells.

The hematocrit of the unit varies depending on the preservative solution. In the United States, commonly used solutions include CPDA-1 (citrate, phosphate, dextrose, adenine) with a hematocrit of 65% to 70% and nutrient preparations such as Adsol (AS-1; adenine, glucose, mannitol, sodium chloride) and Nutricel (AS-2; citrate, phosphate, glucose, adenine, sodium chloride) with a lower hematocrit of 50% to 60%. RBCs in the nutrient solutions (AS-1, AS-2) can be used for up to 42 days after collection, and those preserved in CPDA-1, for up to 28 days.38-40 If a single unit is designated for a preterm infant and is used until its expiration date, up to 13 transfusions can be obtained from a single donor unit, which greatly decreases donor exposure.41

Investigators in Canada hypothesized that fresh RBC transfusions administered to preterm infants would result in lower rates of organ dysfunction, nosocomial infection, and length of stay. A randomized trial on the effect of fresh RBC transfusions on clinical outcomes in premature VLBW infants (ARIPI) demonstrated no benefit to fresh RBC transfusion (red cells stored for ≤7 days) compared with transfusions using RBCs stored under standard blood bank practice.42 The study showed no difference in the primary composite outcome of major neonatal morbidities (e.g., NEC, ROP, BPD, IVH) between groups of infants who received fresh RBCs (mean age of RBCs, 5.1 ±2.1 days) and those administered standard transfusions (mean age of RBCs, 14.6 ±8.3 days). Infants in the fresh RBC group were exposed to a greater number of donors compared with the standard RBC group (3.7 ±2.7 vs. 2.1 ±1.6 donors). Results of this study support the current storage time practices used in most NICUs in the United States.

Transfusion studies in adults have evaluated outcomes based on specific characteristics of the donors.43 A recent retrospective cohort study evaluated outcomes of 31,118 patients who received 59,320 RBC transfusions exclusively from male donors, female donors who had been pregnant, or female donors who had never been pregnant. Mortality rates of transfusion recipients differed among the three groups and between male and female recipients. Among patients who received RBC transfusions, a transfusion from a female donor who had been pregnant, compared with a male donor, was associated with increased all-cause mortality among male recipients but not among female recipients. Transfusions from never-pregnant female donors were not associated with increased mortality among male or female recipients. This distinction in donor characteristics has yet to be explored in neonatal transfusion recipients and may impact future transfusion practices.