Red blood cell transfusion in infants and children: Selection of blood products

INTRODUCTION — Red blood cell (RBC) transfusions are given to children for a wide range of indications, including anemia due to congenital or acquired disease as well as blood loss from trauma or surgery. Once the decision to transfuse RBCs has been made, the most appropriate RBC product must be chosen. Donated whole blood used for transfusion is modified in several ways that remove varying proportions of non-RBC components, thereby allowing selection of RBC products based upon clinical needs.

This topic will review the different RBC products and indications for their use in infants (beyond the neonatal period) and children. RBC transfusion in neonates and other aspects of RBC transfusion in infants and children are discussed separately:

●(See "Red blood cell transfusion in infants and children: Indications".)

●(See "Red blood cell transfusion in infants and children: Administration and complications".)

●(See "Red blood cell (RBC) transfusions in the neonate".)

RED BLOOD CELL PRODUCTS

Red blood cells — RBCs are the blood product of choice for replacement during surgery, blood loss, and sporadic transfusion therapy.

Hematocrit — The hematocrit of RBC units can range from 55 to 80 percent depending upon the preservative solution used:

●Units with anticoagulant-preservative solutions such as citrate-phosphate-dextrose-adenine (CPDA-1), anticoagulant citrate-dextrose A (ACD-A), citrate-phosphate-dextrose (CPD), and citrate-phosphate-dextrose-dextrose (CP2D) typically have a hematocrit of 65 to 80 percent [1].

●Units with additive solutions such as AS-1 (Adsol), AS-3 (Nutricel), AS-5 (Optisol), and AS-7 (SOLX) have a hematocrit of 55 to 65 percent.

Storage duration — RBC units can be stored refrigerated for up to 42 days, but few units are stored that long because there is usually constant turnover in the blood bank inventory. The average storage duration of RBC units transfused in the United States is approximately two to three weeks [2].

The shelf life depends on the anticoagulant-preservative solution used:

●CPDA-1 can be used for 35 days after collection. ACD-A, CPD, and CP2D have a shelf life of 21 days.

●RBC units with additive solutions (eg, AS-1 [Adsol], AS-3 [Nutricel], AS-5 [Optisol], and AS-7 [SOLX]) can be used for 42 days after collection [1].

The available evidence suggests that there is no advantage to using fresh RBCs (storage duration ≤7 days) rather than RBCs with longer storage duration [3-5].

In a multicenter trial involving 1538 critically ill children (including medical, surgical, and trauma patients) randomized to receive either fresh RBCs (median storage duration five days) or standard-issue RBCs (median storage duration 18 days), rates of new-onset multiorgan dysfunction, sepsis, acute respiratory distress syndrome, and mortality were similar in both groups [3]. Similar findings were noted in a smaller trial involving children with severe anemia chiefly due to malaria or sickle cell disease (SCD) [4].

Clinical trials in other populations, including preterm neonates and adult patients, have reached similar conclusion [5]. Those data are discussed in separate topic reviews. (See "Practical aspects of red blood cell transfusion in adults: Storage, processing, modifications, and infusion", section on 'RBC age/storage duration effect on clinical outcomes' and "Red blood cell (RBC) transfusions in the neonate", section on 'Selection of RBC products'.)

Leukoreduced red blood cells — "Leukoreduction" refers to the removal of white blood cells (WBCs) from blood products at time of collection by highly efficient filters that reduce the number of WBCs by >99.9 percent, generally to <1 × 10⁶ WBCs per RBC unit [2]. Though this process greatly reduces the number of WBCs, the few remaining WBCs are capable of replication and can cause transfusion-associated graft-versus-host disease (TA-GVHD) in susceptible individuals. Thus, leukoreduction alone is insufficient to prevent TA-GVHD and patients at risk for TA-GVHD require leukoreduced and irradiated RBC units, as discussed below. (See 'Irradiated red blood cells' below.)

Indications — Many blood banks in the United States, Canada, and other countries have adopted a policy of "universal leukoreduction," in which all RBC and apheresis platelet products are leukoreduced [6]. However, there is variation in practice and ongoing debate about the cost effectiveness of this approach. The clinician should be aware of the policies of the local blood center. If the local blood center does not use universal leukoreduction, leukoreduced products should be specifically ordered when they are desired [7].

While acknowledging local variation in transfusion policies and the need for individualized clinical judgment, we generally agree with guidelines developed by pediatric transfusion medicine specialists and suggest using leukoreduced RBC units for patients requiring RBC transfusions in the following clinical settings [7]:

●Patients who have experienced febrile nonhemolytic transfusion reactions to prevent recurrence [8].

●Patients who require frequent transfusions (eg, those with aplastic anemia, malignancies, or otherwise depended on chronic transfusions) to reduce the risk of human leukocyte antigen (HLA) alloimmunization.

●Future transplant candidates to reduce the risk of HLA alloimmunization.

●Patients at risk for cytomegalovirus (CMV)-related disease to prevent CMV transmission, as described below. (See 'Cytomegalovirus-reduced-risk products' below.)

●Patients undergoing cardiopulmonary bypass to prevent lung injury.

●Neonates – Leukoreduction is generally used for all RBC transfusions to neonates, primarily because this practice reduces the risk for CMV infection [9,10]. There may be additional benefits in preterm neonates [11]. Transfusion in neonates and prevention of CMV infection are discussed in greater detail separately. (See "Overview of cytomegalovirus infections in children", section on 'Blood products and organ donors'.)

Benefits of leukoreduction — The use of leukoreduced RBCs reduces the risk of the following adverse consequences of transfused WBCs:

●Febrile nonhemolytic transfusion reaction – Febrile nonhemolytic transfusion reactions appear to be mediated by leukocyte-derived cytokines and direct donor cell leukocyte interactions. Leukoreduction significantly reduces but does not completely eliminate these reactions [8]. (See "Immunologic transfusion reactions", section on 'Febrile nonhemolytic transfusion reactions'.)

●HLA alloimmunization – HLA alloimmunization can be induced by HLA antigens expressed on donor leukocytes in recipients who receive multiple transfusions. Allosensitization increases the risk of graft rejection in children who subsequently receive organ or hematopoietic stem cell transplantation (HSCT). It also increases platelet refractoriness in patients who need multiple platelet transfusions, (eg, children with leukemia or other malignancies). Leukoreduction reduces the incidence of alloimmunization. (See "HLA-haploidentical hematopoietic cell transplantation", section on 'Donor-specific HLA antibodies' and "Refractoriness to platelet transfusion", section on 'Alloimmunization'.)

●Infection – Leukoreduction reduces the transmission of infectious agents that are harbored in WBCs, notably CMV [2,12]. (See "Overview of cytomegalovirus infections in children", section on 'Blood products and organ donors'.)

●Transfusion-associated immunomodulation (TRIM) – Transfusion of allogeneic blood has an immunosuppressive effect, which is known as TRIM. WBCs play a major causative role in TRIM, and leukoreduction is thought to reduce immunosuppression, but this purported benefit of leukoreduction is not well established and is controversial [13,14].

TRIM may also result in autoimmune tissue damage, as illustrated in a study of young children undergoing surgery for congenital heart disease [15]. Patients who received leukoreduced blood had lower levels of malondialdehyde (a marker of cardiac ischemic injury) compared with those who received blood without leukoreduction. Despite these reports, the role of leukoreduction in decreasing TRIM remains uncertain.

In addition to reducing adverse effects of RBC transfusion, it has been suggested that the removal of WBCs makes transfusion physically easier, especially through the small catheters that may be required in newborns [16]. However, evidence to support this is limited.

Cytomegalovirus-reduced-risk products — Many hospitals use the term "CMV-reduced-risk" (or "CMV-safe") to describe blood products that are either leukoreduced or seronegative [2,17]. However, it remains unclear whether leukoreduction and CMV-seronegative products are equivalent [18-21]. Note that irradiation does not produce a CMV-safe product, because the dose of irradiation used is not sufficient to kill viruses.

The transmission of CMV by transfusion is well known. CMV-reduced risk RBCs should be used for the following populations (see "Overview of cytomegalovirus infections in children", section on 'Blood products and organ donors'):

●Preterm infants born to CMV-seronegative mothers [22,23]; CMV infection in neonates can range in severity from asymptomatic infection to a severe life-threatening disease. Symptomatic CMV infection is more common in infants born to CMV-negative mothers. Some neonatal intensive care units use CMV-seronegative RBCs for all neonates in addition to leukoreduction [20]. (See "Overview of cytomegalovirus infections in children", section on 'Early postnatal infection'.)

●Infants and children with congenital or acquired immunodeficiency (known or suspected), including CMV-seronegative children receiving HSCT or solid organ transplants from CMV-negative donors.

●CMV-seronegative children receiving HSCT or solid organ transplants from CMV-positive donors; in addition to using leukoreduced or CMV-seronegative blood for transfusion, these patients are generally treated with prophylactic or preemptive antiviral agents.

●Fetuses receiving intrauterine transfusions [7].

The risk of CMV transmission is eliminated almost entirely by the transfusion of blood from donors who are CMV seronegative. However, rare transmission of CMV has been documented when the donor is viremic and in the "window period" following exposure to the virus, before the development of antibodies, or when the antibody titer is below the limits of detection [24-27].

In settings where the seropositivity for CMV is high, there may be insufficient CMV-seronegative donors to fill the need for CMV-safe blood products. For example, in the Unites States, 40 to 90 percent of donors are CMV seropositive. For this reason, blood donor centers in the United States provide leukoreduced blood products more commonly than seronegative blood products when CMV-safe blood is required. Fortunately, leukoreduction is effective in reducing the risk of transmission of CMV. However, rare cases of CMV have been associated with transfusion of either leukoreduced or seronegative blood products [28].

Irradiated red blood cells

Rationale — Irradiated RBCs are used in patients at risk for TA-GVHD. TA-GVHD is caused by viable donor lymphocytes that are transfused into a patient who either does not recognize these cells as foreign or does not have the capacity to destroy them. TA-GVHD usually begins 8 to 10 days following transfusion and is almost inevitably fatal. (See "Transfusion-associated graft-versus-host disease".)

Exposure of the blood product to gamma or x-ray irradiation at a standard dose prior to transfusion stops proliferation of foreign lymphocytes, which entirely prevents TA-GVHD. However, the dose of radiation used for cellular blood products is not sufficient to kill viruses. Thus, irradiation does not provide a CMV-safe product and does not eliminate the need for either leukoreduction or CMV-seronegative blood products if a CMV-safe product is required [7]. Conversely, leukoreduction does not eliminate all viable donor lymphocytes and leukoreduced but nonirradiated products can result in TA-GVHD. (See 'Cytomegalovirus-reduced-risk products' above and 'Leukoreduced red blood cells' above and "Transfusion-associated graft-versus-host disease", section on 'Prevention'.)

Indications — TA-GVHD is extremely rare because the donor lymphocytes are destroyed by the recipient's immune system. However, this protective response does not occur in two settings, thus necessitating the use of irradiated RBCs:

●Immunodeficient recipients – Patients with decreased cellular immunity may be unable to mount a response against the transfused donor lymphocytes. Settings in which this complication can occur include (table 1) [7,29]:

•Children with hematologic disorders who will undergo HSCT

•Children with Hodgkin lymphoma

•Intrauterine transfusions

•Preterm infants weighing less than 1200 g at birth [7]

•Neonatal exchange transfusions

•Children with congenital cell-mediated immunodeficiencies (eg, severe combined immunodeficiency or DiGeorge syndrome)

•Children with severe immunosuppression due to chemotherapy or irradiation for oncologic or autoimmune disease

•Children with immunosuppression who have received HSCT

•Solid organ transplant recipients, particularly those treated with antithymocyte globulin; some, but not all, institutions use irradiated blood in all solid organ transplant recipients

●"Directed donor" blood products – In immunocompetent individuals, TA-GVHD may develop in a partial HLA match when the recipient is heterozygous at an HLA allele for which the donor is homozygous. In these instances, donor WBCs will not be recognized as foreign by the host, but the donor cells may recognize host cells as foreign and mount a TA-GVHD reaction. There is an increased likelihood of this occurring in blood relatives or if the donor and recipient are members of a population that is genetically homogeneous. As a result, blood products donated by family members should be irradiated before transfusing into a blood relative. (See "Transfusion-associated graft-versus-host disease", section on 'Partial HLA matching'.)

TA-GVHD has been rarely reported in low birth weight newborns [30]. Although the need for irradiated blood products in neonates is controversial [31,32], many, but not all, institutions routinely irradiate blood for newborns or at least for preterm newborns [10].

Side effects — Irradiation of RBC units can injure the RBC membrane, leading to the following disadvantages:

●Reduced shelf life – The shelf life of irradiated RBC units is reduced to 28 days after irradiation or original expiration, whichever comes first. (See "Practical aspects of red blood cell transfusion in adults: Storage, processing, modifications, and infusion", section on 'Irradiation'.)

●Elevated potassium – Irradiated RBC units tend to have increased concentrations of potassium since the potassium level increases during storage after irradiation. This disadvantage is particularly relevant for the pediatric age group. For the ordinary, small-volume, slow transfusion levels of potassium in a unit are safe at any time before expiration, whether or not the unit has been irradiated [32]. However, clinically significant hyperkalemia can occur in certain unusual clinical situations, such as infusion of this blood into the heart during extracorporeal membrane oxygenation (ECMO) cannulation or other instances of massive and rapid transfusion into a central line [32-34]. As an example, one case report described hyperkalemia in an infant following the transfusion of RBCs that were six days old and had been irradiated 48 hours prior to transfusion [35].

To minimize increases in serum potassium, irradiation of RBCs should be performed shortly before transfusion to decrease the amount of potassium leak. However, this may not be possible in all cases, particularly in hospitals that do not have an irradiator on site.

For patients who are receiving massive transfusion (defined as replacement >50 percent of a patient's blood volume in three hours, those receiving exchange transfusions, or other clinical settings with anticipated large volumes of transfused blood), the supernatant solution containing excess potassium can be removed by washing the RBCs prior to transfusion if freshly irradiated RBCs are not available. Washing of irradiated RBCs is the most effective method for removing excess potassium [36]. Washing of irradiated RBCs should be reserved for selected situations since it reduces the volume of RBCs available and may minimize the efficacy of the transfusion [36].

Whole blood — Transfusion of whole blood has limited use in pediatric patients. It is not readily available in many settings, including most hospitals in the United States. Whole blood (either collected and transfused or reconstituted [RBCs combined with plasma]) is most commonly used in clinical circumstances when it is desirable to use a blood product with a lower hematocrit than that of an RBC unit (eg, patients undergoing cardiopulmonary bypass, ECMO, exchange transfusion, or massive transfusion). Interest in using group O whole blood with a low titer anti-A and anti-B has been increasing, especially in patients with severe trauma who require massive transfusion [37-39]. The rationale for use is that it provides RBCs, plasma, and platelets in an appropriate ratio in a single transfusion. (See 'Massive transfusion' below and "Trauma management: Approach to the unstable child", section on 'Massive transfusion protocol'.)

The use of fresh whole blood for children undergoing cardiac surgery on cardiopulmonary bypass is not a standard practice. In the past, fresh whole blood (generally <48 hours old) was used for infants undergoing cardiopulmonary bypass because early clinical trial data suggested that it may improve hemostasis [40]. However, a subsequent randomized trial did not detect differences in hemostasis and there was a suggestion that using fresh whole blood in this setting contributed to perioperative fluid overload [41].

Sickle cell-negative blood — Blood that is "sickle cell negative" has been tested by a rapid screen for the presence of hemoglobin S (HbS). A negative screen indicates that the blood contains <30 percent HbS.

Cells that contain >30 percent HbS might sickle in vivo under hypoxic conditions. Therefore, sickle cell-negative blood is usually used for transfusion to patients in the following categories [2]:

●Newborns

●Intrauterine transfusions

●Exchange transfusion

●Transfusions for patients with SCD [42]

Autologous and directed donations — Autologous and directed donations increased dramatically in response to the acquired immunodeficiency syndrome (AIDS) epidemic, but these practices are rarely used in the modern era since the safety of blood products has improved.

●Preoperative autologous donation (PAD) – PAD refers to blood donated by an individual exclusively for their own use. Historically, PAD was commonly used in the setting of elective surgery that is expected to require blood transfusion (eg, scoliosis surgery). In the modern era, many hospitals discourage PAD unless there is a clear indication (ie, patients with a rare RBC phenotype or antibodies to multiple RBC antigens, for whom compatible blood is not readily available) [43]. PAD is discussed in greater detail separately. (See "Surgical blood conservation: Preoperative autologous blood donation".)

●Directed donations – Directed donations refers to one individual (typically a relative of the patient) donating units to be used for a particular patient. Most centers discourage directed donation since they generally do not provide a benefit for recipients and they carry increased administrative burdens. However, they may be appropriate in select circumstances (eg, when a recipient has antibodies to high-frequency antigens or when there is a need to reduce recipient exposure to certain antigens on RBCs). Directed donation is discussed in greater detail separately. (See "Blood donor screening: Overview of recipient and donor protections", section on 'Directed donations'.)

COMPATIBILITY TESTING (CROSSMATCHING)

Older infants and children — For individuals four months of age and older, standard protocols for compatibility testing apply. (See "Pretransfusion testing for red blood cell transfusion".)

Newborns and young infants — For infants <4 months of age, maternal antibodies to RBC antigens may be present; fetal antibody production is limited. In emergency situations, any young infant requiring transfusion can be issued group O, RhD-negative RBCs. In nonemergency settings, the infant's blood is tested for ABO and RhD type and a screen is performed for unexpected RBC antibodies using plasma or serum from the infant or mother [2]. Testing for anti-D is particularly critical because this antibody is found in infants whose mothers were given RhD immune globulin.

There are two approaches to RBC transfusion in newborns and young infants: use of group O, RhD-negative blood for all infants or use of ABO- and RhD-compatible RBCs. Institution-specific guidelines should be followed; these are generally developed based on the frequency of newborn transfusions and available blood products:

●Group O, RhD-negative RBCs for all infants – Some institutions use this approach for all transfusions to infants <4 months old to simplify blood banking procedures. Possible risks of this approach are that the group O RBCs may include a small amount of anti-A and anti-B in the associated plasma, which can cause hemolysis in the infant with blood type A, B, or AB. This concern is most relevant in preterm infants because of their small blood volume. Some institutions wash the RBC prior to transfusion to remove these antibodies and reduce the risk of hemolysis; this can also be done for preterm infants. Another challenge of this approach is that it can contribute to shortages of group O RhD-negative RBCs.

●ABO- and RhD-compatible RBCs – Some institutions issue ABO- and RhD-compatible RBCs. In this case, the infant must also be tested for "passive" anti-A and/or anti-B depending on the infant's ABO (ie, anti-A or anti-B of maternal origin). These antibodies are detected by an indirect antiglobulin (Coombs) test, which can be done on the infant's plasma. If anti-A or anti-B are detected, RBCs lacking the corresponding antigen must be transfused.

Infants requiring transfusion because of hemolytic disease of the fetus and newborn require additional considerations when selecting RBCs for transfusion, as outlined in a separate topic review. (See "Red blood cell (RBC) transfusions in the neonate", section on 'Alloimmune hemolytic disease of the newborn'.)

Other aspects of RBC transfusion in the newborn, including the indications and administration, are discussed in separately. (See "Red blood cell (RBC) transfusions in the neonate".)

If the initial antibody screen is negative, compatibility testing may be omitted during the same hospitalization for most infants up to four months of age [2,44]. This is because infants do not usually develop alloantibodies against RBCs in response to transfusions until at least four months of age [45]. This approach minimizes the amount of blood that must be drawn from small infants for laboratory testing. A newborn may acquire passive anti-A or anti-B through a transfusion of ABO-incompatible plasma or platelets or through massive transfusion. In this case, a transfusion of group O RBC may be given. Alternatively, immediate spin crossmatching may be performed if group A or group B RBCs are given.

SPECIFIC CLINICAL SITUATIONS

Hematopoietic stem cell transplantation — Many hematopoietic stem cell transplants (HSCT) occur from ABO-incompatible donors. Transfusion in this setting can be complex because erythroid engraftment may be delayed if the recipient has strong antibodies to donated cells. Generally, donor type O or compatible RBCs are washed to remove incompatible plasma. Products containing plasma should be compatible with both donor and recipient cells. These precautions are continued until recipient antibodies are no longer detected. (See "Hematopoietic support after hematopoietic cell transplantation", section on 'Red blood cells'.)

Emergency release of blood — When blood is needed urgently, it may be provided uncrossmatched through an emergency release process that is available in all blood banks. If the child's ABO group and RhD type are known to the blood bank on the current specimen, ABO compatible RBCs and other components will be provided, without crossmatching. If the group and type are not known, O RBCs and AB platelets and plasma are used; if the recipient is a female, the RBCs should be RhD-negative to avoid RhD sensitization that could affect a future pregnancy.

Uncrossmatched blood for emergency transfusion is generally safe, particularly if the child has not been previously transfused and cannot be expected to have developed RBC antibodies. (See "Pretransfusion testing for red blood cell transfusion", section on 'Emergency release blood for life-threatening anemia or bleeding'.)

Massive transfusion — Massive transfusion in pediatric patients is usually defined as any one of the following [46,47]:

●Transfusion of >50 percent of total blood volume within three hours

●Transfusion of >100 percent of total blood volume in 24 hours

●Transfusion support to replace ongoing blood loss of >10 percent of total blood volume per minute

Type-specific blood is used without further serologic testing. Massive transfusion increases the risk for a variety of metabolic and hemostatic abnormalities, particularly in neonates and infants. Dilutional coagulopathy may occur if only RBCs have been transfused; as a result, plasma and platelets should be included for patients receiving a massive transfusion. Trauma also can contribute to an acute coagulopathy, through a variety of mechanisms. Electrolytes and acid-base balance should be monitored carefully since the large amount of stored blood products transfused in this setting may lead to serious hyperkalemia [32]. Hypokalemia associated with metabolic alkalosis is also possible due to the large amount of citrate metabolized to bicarbonate. Other abnormalities associated with massive transfusion include hypocalcemia, hyper- or hypoglycemia, and hypothermia. (See "Red blood cell transfusion in infants and children: Administration and complications", section on 'Metabolic toxicity' and "Massive blood transfusion".)

Alloantibodies in sickle cell disease — Patients with sickle cell disease (SCD) undergo repeated transfusions and often develop alloantibodies. Approximately 30 to 40 percent of patients with SCD will develop at least one antibody and, over the course of years of transfusion, multiple antibodies. In order to find compatible units for transfusion, it may be necessary to procure units of RBCs from a rare donor bank; however, even with this strategy, it may be impossible to provide fully compatible blood. Some patients with SCD develop autoantibodies and/or have an unexplained delayed hemolytic transfusion reaction, a phenomenon that is poorly understood. Hemolysis also may occur in the absence of RBC antibodies; this condition is known as "hyperhemolysis syndrome" and is characterized by an acute decrease in hemoglobin after the transfusion. The direct antiglobulin test (DAT; also known as Coombs test) is usually negative. The patient's reticulocyte count also drops from the baseline [48]. (See "Overview of the clinical manifestations of sickle cell disease", section on 'Hyperhemolytic crisis' and "Transfusion in sickle cell disease: Management of complications including iron overload", section on 'Alloimmunization and hemolysis'.)

Extended phenotype matching for other RBC antigens to minimize the risk of alloimmunization, as well as other considerations such as leukoreduction, are discussed separately. (See "Red blood cell transfusion in sickle cell disease: Indications and transfusion techniques", section on 'Transfusion techniques'.)

Autoimmune hemolytic anemia — In infants and children with autoimmune hemolytic anemia, a condition in which the patient's RBCs are destroyed by autoantibodies, transfusion can be challenging because most autoantibodies are reactive with virtually all RBCs (ie, "panreactive"). As a result, every available donor unit may appear to be incompatible by crossmatch. It is important for the blood bank to exclude the simultaneous presence of alloantibodies that have developed from previous transfusion(s). If underlying alloantibodies can be excluded, hemolytic transfusion reactions will be rare even if the blood that is incompatible is used. Despite the risks, it is important to ensure that transfusion therapy should never be withheld from a patient with autoimmune hemolytic anemia and life-threatening anemia. (See "Red blood cell (RBC) transfusion in individuals with serologic complexity", section on 'Alloantibodies' and "Autoimmune hemolytic anemia (AIHA) in children: Treatment and outcome", section on 'Severe or life-threatening anemia'.)

SOCIETY GUIDELINE LINKS — Links to society and government-sponsored guidelines from selected countries and regions around the world are provided separately. (See "Society guideline links: Transfusion and patient blood management".)

SUMMARY AND RECOMMENDATIONS

●Red blood cell (RBC) products – RBC transfusions are given to children for a wide range of indications. Though the basic RBC unit is the product most commonly used, many modifications to the basic unit are available for transfusion and the correct product varies with the clinical setting. Transfusion medicine personnel can help to determine the correct blood product based on the relevant clinical information. (See 'Introduction' above and 'Red blood cell products' above.)

RBC products used in infants and children include:

•Leukoreduced RBCs – Leukoreduction removes white blood cells (WBCs) from blood products using special filters. Leukoreduction is widely used in infants and children to reduce febrile nonhemolytic transfusion reactions, prevent alloimmunization, and reduce the transmission of certain infections (notably cytomegalovirus [CMV]). However, leukoreduction does not eliminate all lymphocytes. Therefore, blood products given to patients at risk for transfusion-associated graft-versus-host disease (TA-GVHD) should also be irradiated. (See 'Leukoreduced red blood cells' above and 'Irradiated red blood cells' above.)

•CMV-reduced-risk RBCs – The term "CMV-reduced-risk" (or "CMV-safe") is typically used to describe products that are either leukoreduced or CMV seronegative. Use of either of these products reduces the transmission of CMV. These products are recommended for CMV-seronegative recipients with special risks for CMV disease. (See 'Cytomegalovirus-reduced-risk products' above.)

•Irradiated RBCs – Irradiation of RBCs prevents TA-GVHD in susceptible recipients. Indications for irradiation include directed donor blood products that will be transfused into a blood relative and immunodeficiency due to a variety of conditions in which the transfusion recipient is at risk for TA-GVHD (table 1). The dose of irradiation is not sufficient to kill viruses, and, thus, irradiation does not provide a CMV-safe product. (See 'Irradiated red blood cells' above and 'Cytomegalovirus-reduced-risk products' above.)

•Sickle cell-negative blood – Sickle cell-negative blood (hemoglobin S [Hbs] <30 percent) is usually used for transfusion to newborns, intrauterine transfusions, and patients with sickle cell disease (SCD). (See 'Sickle cell-negative blood' above.)

●Special circumstances – Unique considerations may impact the choice of blood product in the following clinical scenarios (see 'Specific clinical situations' above):

•Hematopoietic stem cell transplantation (HSCT) (see 'Hematopoietic stem cell transplantation' above and "Hematopoietic support after hematopoietic cell transplantation", section on 'Red blood cells')

•Emergency release of blood (see 'Emergency release of blood' above and "Pretransfusion testing for red blood cell transfusion", section on 'Emergency release blood for life-threatening anemia or bleeding')

•Massive transfusion (see 'Massive transfusion' above and "Massive blood transfusion")

•SCD (see 'Alloantibodies in sickle cell disease' above and "Red blood cell transfusion in sickle cell disease: Indications and transfusion techniques")

•Autoimmune hemolytic anemia (see 'Autoimmune hemolytic anemia' above and "Red blood cell (RBC) transfusion in individuals with serologic complexity", section on 'Autoantibodies')