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Red blood cell transfusion in infants and children: Indications

Red blood cell transfusion in infants and children: Indications
Literature review current through: Jan 2024.
This topic last updated: Apr 07, 2023.

INTRODUCTION — Transfusion of red blood cells (RBCs) can be lifesaving in patients with severe blood loss or severe chronic anemia. However, RBC transfusion has risks, including volume overload, transmission of infectious agents, transfusion reactions, and various immunologic consequences (including graft-versus-host disease).

The indications for RBC transfusion in infants and children will be reviewed here. Other aspects of transfusion in infants and children are discussed in separate topic reviews:

(See "Red blood cell transfusion in infants and children: Selection of blood products".)

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

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

(See "Pretransfusion testing for red blood cell transfusion".)

PREVALENCE OF PEDIATRIC RED BLOOD CELL TRANSFUSION — Approximately 1 to 3 percent of hospitalized children receive RBC transfusions [1,2].

In a study analyzing data on >1,000,000 non-neonatal pediatric admissions from the 2016 Kid's Inpatient Database, RBC transfusions were administered in 2.6 percent [2]. RBC transfusion was more common in elective admissions compared with nonelective (presumably because elective admissions more often were surgical patients). RBC transfusion correlated with severity of illness, hospital length of stay, and risk of mortality.

GENERAL PRINCIPLES

Rationale for transfusion — Optimal transfusion practice is aimed at ensuring sufficient circulating RBCs to prevent or reduce morbidity and mortality associated with anemia while avoiding unnecessary transfusions. The principal rationale behind RBC transfusion is to provide sufficient cells to prevent or reverse tissue hypoxia due to limited oxygen delivery. There are limited data on the hemoglobin [Hgb] level required for sufficient tissue oxygenation in healthy children, but data from animal studies and clinical observations of children with chronic hemolytic anemia suggest that a hematocrit of 20 percent (which corresponds to a Hgb of approximately 6.7 g/dL) can generally be tolerated without adverse consequences [3,4]. The risk of mortality and other adverse outcomes increases with Hgb levels <5 g/dL (hematocrit <15 percent) [5,6].

Restrictive versus liberal strategy — For most patients, a restrictive transfusion strategy (ie, giving less blood, transfusing at a lower Hgb level, and aiming for a lower target Hgb level) is sufficient rather than a liberal transfusion strategy (ie, giving more blood, transfusing at a higher Hgb level).

For hemodynamically stable hospitalized pediatric patients, including hemodynamically stable children with critical illness, we recommend a restrictive RBC transfusion strategy (ie, Hgb of 7 g/dL as the transfusion threshold) rather than more liberal transfusion strategies. The available clinical trial data suggest that using restrictive transfusion thresholds reduces exposure to RBC transfusions without increasing mortality or serious morbidity [7,8].

Transfusion at higher Hgb levels may be appropriate in certain conditions such as acute blood loss from trauma or surgery, cyanotic congenital heart disease (CHD), malignancy, and chronic anemias (eg, sickle cell disease, thalassemia). (See 'Specific clinical scenarios' below.)

Factors in clinical decision-making — When making decisions about whether to transfuse, the following factors should be considered:

Degree of anemia (Hgb level) – In both children and adults, clinicians have sought a "transfusion trigger": an absolute Hgb value below which the patient needs RBC transfusion. However, clinicians should not use the Hgb alone as the sole basis for decision-making. Assigning an absolute level is difficult since the impact of a given degree of anemia varies with the clinical setting (eg, acute or chronic) and physiologic status of the patient. In addition, the physiologic response to anemia in children is different from adults. In children, dyspnea, impaired consciousness, and other symptoms of hemodynamic compromise may not appear until the Hgb is <6 g/dL (hematocrit <18 percent) if the anemia has developed slowly. In critically ill children who are stable (ie, not actively bleeding and without refractory shock or hypoxemia), an Hgb threshold of 7 g/dL (hematocrit of 21 percent) has been used to decrease transfusion requirements without increasing adverse outcomes [7].

The minimum Hgb concentration that can be tolerated without mortality or morbidity is not necessarily the optimum Hgb concentration to support growth and normal activities in children. Whatever the optimum value, actual RBC transfusion practice should be a balance between that value and the associated risks of transfusion. Complications of RBC transfusion are discussed in detail separately. (See "Red blood cell transfusion in infants and children: Administration and complications", section on 'Complications'.)

There are few studies of RBC transfusion requirements in children except in certain specific patient populations, such as children with sickle cell disease, critically ill children, premature neonates, and African children with severe anemia [7,9-12]. The available published guidelines regarding RBC transfusion in infants and children are based largely on observational data, a few clinical trials, and extrapolation of studies in adult patients [13-16].

In general, RBC transfusion is warranted for severe anemia (Hgb levels <5 to 6 g/dL or hematocrit <15 to 18 percent) since the risk of mortality and other adverse outcomes is increased with this degree of anemia [5,6]. Transfusion is generally not indicated in children with Hgb concentrations >10 g/dL (hematocrit >30 percent). In patients with Hgb levels between 6 and 10 g/dL (hematocrit 18 to 30 percent), the decision to transfuse is dependent upon the clinical situation.

Acuity of anemia – Chronically anemic children often tolerate Hgb concentrations as low as 6 to 7 g/dL (hematocrit 18 to 21 percent) because they are able to maintain adequate intravascular volume and tissue oxygenation [17]. On the other hand, patients with an acute loss of blood and hypovolemia may require transfusion, depending on the extent of blood loss. (See 'Chronic anemias' below and 'Trauma' below.)

Degree of symptoms – Symptoms attributable to anemia can also impact the decision to transfuse. Most children have symptoms of anemia at Hgb levels <6 or 7 g/dL (hematocrit <18 to 21 percent) [18]. However, children with chronic anemia may not have symptoms at this level and children with acute blood loss and those with underlying medical conditions may develop symptoms at considerably higher Hgb levels.

Cardiopulmonary stability – Transfusion is often warranted for anemia that is associated with hemodynamic instability, as discussed below. (See 'Critical illness' below.)

Ongoing blood loss – For patients with blood loss from traumatic injuries or surgical blood loss, the decision to transfuse should consider whether there is ongoing blood loss. (See 'Trauma' below and 'Surgery' below.)

Underlying conditions – Higher target Hgb levels may be warranted in patients with underlying medical conditions that are associated with chronic anemia, such as sickle cell disease or leukemia. (See 'Sickle cell disease' below and 'Malignancy' below.)

SPECIFIC CLINICAL SCENARIOS — The following is a brief review of common clinical scenarios in which pediatric patients may require RBC transfusions. Most of these conditions are discussed in detail elsewhere.

Neonates — Common reasons for RBC transfusion in neonates include hemolytic disease of the fetus and newborn, perinatal blood loss, anemia of prematurity, and iatrogenic withdrawal of blood for laboratory testing. (See "Alloimmune hemolytic disease of the newborn: Postnatal diagnosis and management" and "Intrauterine fetal transfusion of red blood cells" and "Anemia of prematurity (AOP)".)

Thresholds for RBC transfusion in newborns are summarized in the table (table 1) and discussed in detail separately. (See "Red blood cell (RBC) transfusions in the neonate", section on 'Indications for transfusion'.)

Critical illness

Unstable – Transfusion is often warranted in unstable anemic pediatric patients who have cardiopulmonary compromise (ie, patients with unstable shock and/or severe hypoxemia). In this setting, the need for transfusion is usually determined by clinical parameters rather than the patient's Hgb level, though transfusion is rarely indicated if the Hgb level is >10 g/dL (hematocrit >30 percent) [16,19]. The minimum Hgb target for unstable critically ill patients who are not actively bleeding is uncertain. (See "Septic shock in children in resource-abundant settings: Ongoing management after resuscitation", section on 'Blood transfusion' and "Shock in children in resource-abundant settings: Initial management", section on 'Fluid resuscitation'.)

Hemodynamically stable – The Pediatric Critical Care Blood Research Network (BloodNet) and the Pediatric Acute Lung Injury and Sepsis Investigators Network's consensus recommendations for RBC transfusion in critically ill children provide specific guidance for decision-making in a wide range of clinical scenarios [16]. We agree with the expert panel's recommendation that, for most critically ill children who are hemodynamically stable and not severely hypoxic, RBC transfusion not be given if the Hgb is ≥7 g/dL (hematocrit ≥21 percent). Exceptions to this include children with CHD, acute brain injury, sickle cell anemia, oncologic diseases, recent hematopoietic stem cell transplant, and acute blood loss due to trauma, in whom transfusion may be appropriate at a higher Hgb level, as discussed below. (See 'Congenital heart disease surgery' below and 'Sickle cell disease' below and 'Malignancy' below and 'Trauma' below.)

A clinical trial randomly assigned 637 stabilized (ie, not hypotensive and not requiring escalating cardiovascular treatments) critically ill children to either a restrictive transfusion strategy (Hgb of 7 g/dL as the transfusion threshold) or a liberal strategy (Hgb of 9.5 g/dL as the transfusion threshold) [7]. The restrictive strategy decreased transfusion requirements without increasing adverse outcomes (ie, multiple organ dysfunction syndrome or death).

Trauma — Trauma patients who present with hemodynamic instability often require RBC transfusion if they show little to no improvement with initial crystalloid infusions. (See "Trauma management: Approach to the unstable child", section on 'Blood products'.)

In patients who have profound hemorrhage or ongoing bleeding with an anticipated need to replace total blood volume, a massive transfusion protocol is generally appropriate since transfusion of RBC without platelets and plasma leads to dilutional coagulopathy and may worsen bleeding. (See "Trauma management: Approach to the unstable child", section on 'Massive transfusion protocol' and "Massive blood transfusion".)

Surgery — For children with anemia who are undergoing surgery, management prior to surgery should include evaluation for the cause of anemia and, if warranted, initiation of appropriate treatment (eg, if iron deficiency is identified, iron therapy should be initiated). However, this approach may not be feasible in emergency or urgent procedures. (See "Approach to the child with anemia" and "Iron deficiency in infants and children <12 years: Treatment".)

The decision to provide perioperative RBC transfusion should be individualized based upon the child's diagnosis, the surgical procedure, expected blood loss, and the degree of symptoms attributable to anemia:

Patients with symptoms and/or large blood loss – For children with rapid bleeding, symptomatic anemia (eg, hypotension, tachycardia, or altered mental status), or evidence of tissue hypoxia (eg, lactic acidosis, ischemic changes on electrocardiogram), transfusion is often warranted regardless of the Hgb level. Intraoperative transfusion is generally required if blood loss exceeds 15 percent of blood volume. (See "Intraoperative transfusion and administration of clotting factors", section on 'Red blood cells'.)

Asymptomatic patients – In the setting of asymptomatic anemia, the American Society of Anesthesiologists recommends a restrictive perioperative RBC transfusion strategy (ie, transfusion threshold of Hgb <8 g/dL); however, these guidelines excluded infants and children <35 kg [20]. Children with certain underlying conditions, particularly sickle cell disease and cyanotic CHD, require higher Hgb levels to safely undergo general anesthesia. This issue is discussed in greater detail separately. (See "Red blood cell transfusion in sickle cell disease: Indications and transfusion techniques", section on 'Prophylactic preoperative transfusion'.)

In children, surgeries that are often associated with high risk of blood loss requiring RBC transfusion include congenital heart disease (CHD) surgery, orthopedic surgery (particularly scoliosis surgery), certain plastic surgery procedures (eg, craniosynostosis repair), and certain surgical oncology procedures.

In adults, a variety of interventions have been undertaken to reduce surgical blood use. Many of these techniques can be used in older children without significant alteration of the adult protocols. Large-scale trials of these modalities in children have not been performed, although some reviews of experience are available [21,22]. Strategies used to reduce the need for RBC transfusion include preoperative management to increase Hgb levels and intraoperative interventions including cell salvage and antifibrinolytic agents [23]. These issues are discussed separately. (See "Perioperative blood management: Strategies to minimize transfusions" and "Surgical blood conservation: Intraoperative blood salvage".)

Congenital heart disease surgery — RBC transfusions are frequently required during and following surgical repair or palliation of CHD; however, the optimal target Hgb following CHD surgery is uncertain [16,19,24]. There is limited evidence that a restrictive transfusion strategy (Hgb threshold of 9 g/dL for cyanotic and 7 g/dL for noncyanotic disease) may reduce transfusion-related risks without increasing other adverse outcomes (ie, lactic acidosis, multiorgan dysfunction syndrome, prolonged intensive care length of stay, or death) [9,25-27].

In a randomized trial involving 162 infants with CHD undergoing surgical repair or palliation, patients were randomly assigned to either a postoperative conservative strategy (RBC transfusion for Hgb <7 g/dL for biventricular repairs or <9 g/dL for palliative procedures plus a clinical indication) or liberal strategy (RBC transfusion for Hgb <9.5 g/dL for biventricular repairs or <12 g/dL for palliative procedures regardless of clinical indication) [27]. Fewer infants required postoperative RBC transfusion in the conservative group than in the liberal group (48 versus 80 percent). There were no differences in in-hospital mortality (7 versus 6 percent), need for extracorporeal membrane oxygenation support (3 versus 4 percent), or median hospital length of stay (13 days in both groups). In addition, peak serum lactate levels and arteriovenous oxygen difference were similar in the two groups.

Orthopedic surgery — Certain orthopedic surgeries are often associated with significant blood loss requiring RBC transfusion. This is particularly true of spinal fusion surgery for scoliosis, which can be associated with massive blood loss. The severity of blood loss correlates with the number of osteotomies performed and spinal levels fused [28]. Several techniques have been used to reduce the transfusion rates in pediatric and adult patients undergoing spinal fusion. These include intraoperative blood salvage and antifibrinolytics (eg, tranexamic acid and epsilon-aminocaproic acid) [23]. Other techniques were used in the past (eg, preoperative autologous blood donation, normovolemic hemodilution, intraoperative controlled hypotension), but these have fallen out of favor in the modern era [29]. These issues are discussed in greater detail separately. (See "Anesthesia for elective spine surgery in adults", section on 'Blood loss during spinal surgery' and "Surgical blood conservation: Preoperative autologous blood donation" and "Surgical blood conservation: Acute normovolemic hemodilution".)

Other surgeries — Other surgeries that occasionally require multiple units of RBCs include certain plastic surgery and surgical oncology procedures. In particular, surgical correction of craniosynostosis almost always requires RBC transfusion [30]. Measures that have reduced RBC allogeneic transfusions include the preoperative use of erythropoietin [31] and perioperative blood salvage [32]. (See "Overview of craniosynostosis" and "Perioperative blood management: Strategies to minimize transfusions".)

Malignancy — Children with cancer who are undergoing either cytotoxic chemotherapy or hematopoietic stem cell transplantation represent one of the largest groups of patients requiring frequent RBC transfusion.

Practice varies regarding RBC transfusion thresholds in pediatric cancer patients. One approach is to transfuse at an Hgb level of 6 to 7 g/dL (hematocrit 18 to 21 percent), which, as noted above, is the level at which most children become symptomatic [33]. (See 'Factors in clinical decision-making' above.)

Alternatively, some experts suggest an RBC transfusion threshold of Hgb level <8 g/dL (hematocrit <24 percent) to avoid the development of symptoms, particularly if ongoing chemotherapy-associated marrow suppression is likely [16,34]. Transfusion may also be warranted at higher Hgb levels if there are symptoms attributable to anemia.

Among pediatric patients undergoing hematopoietic stem cell transplant, observational data suggest that a restrictive transfusion strategy may reduce transfusion requirements without increasing adverse outcomes [35]. This is discussed in greater detail separately. (See "Hematopoietic support after hematopoietic cell transplantation", section on 'Transfusion support'.)

Chronic kidney disease — Anemia in children with chronic kidney disease is usually managed with iron supplementation and erythropoiesis-stimulating agents; RBC transfusion is not necessary for most patients. Management of anemia in chronic kidney disease is discussed in greater detail separately. (See "Chronic kidney disease in children: Complications", section on 'Anemia'.)

Chronic anemias

Sickle cell disease — Children with sickle cell disease commonly are transfused for the following indications (see "Red blood cell transfusion in sickle cell disease: Indications and transfusion techniques", section on 'Indications for transfusion'):

Acute chest syndrome (see "Acute chest syndrome (ACS) in sickle cell disease (adults and children)", section on 'Transfusion')

Acute stroke and primary and secondary stroke prevention (see "Acute stroke (ischemic and hemorrhagic) in children and adults with sickle cell disease", section on 'TIA and ischemic stroke management' and "Prevention of stroke (initial or recurrent) in sickle cell disease", section on 'Prevention of a first ischemic stroke (primary stroke prophylaxis)' and "Prevention of stroke (initial or recurrent) in sickle cell disease", section on 'Prevention of recurrent ischemic stroke (secondary stroke prophylaxis)')

Aplastic crisis and splenic sequestration crisis (see "Red blood cell transfusion in sickle cell disease: Indications and transfusion techniques", section on 'Symptomatic or severe anemia')

Prevention of recurrent priapism (see "Priapism and erectile dysfunction in sickle cell disease", section on 'Regular red blood cell transfusions')

Reduction of perioperative complications using preoperative transfusion (see "Red blood cell transfusion in sickle cell disease: Indications and transfusion techniques", section on 'Prophylactic preoperative transfusion')

Transfusion in many of these conditions serves not only to increase oxygen delivery, but also to reduce vaso-occlusion by decreasing the percentage of sickle Hgb. Details of transfusion techniques, complications, and use of simple versus exchange transfusions are discussed separately. (See "Red blood cell transfusion in sickle cell disease: Indications and transfusion techniques".)

Thalassemia — Thalassemia refers to a spectrum of diseases characterized by the absence or reduction of one or more globin chains in the Hgb molecule. RBC transfusion requirements vary among the different types of thalassemia as follows (algorithm 1):

Beta thalassemia major – Patients with beta thalassemia major (also called transfusion-dependent thalassemia) are typically managed with chronic transfusions and iron chelation therapy. (See "Management of thalassemia", section on 'Management of anemia'.)

Thalassemia intermedia – Children and adolescents with thalassemia intermedia may require transfusions during periods of erythropoietic stress such as acute infectious illnesses, periods of rapid growth, or surgery. Some patients may require chronic transfusion therapy as they reach adulthood.

Thalassemia minor – Transfusions are not required, since anemia is very mild or absent.

Alpha thalassemia – Survival of infants with severe degrees of alpha thalassemia (eg, hemoglobin Barts) has improved following the introduction of intrauterine or early postnatal transfusion, but continued chronic transfusion is required [36]. Patients with hemoglobin H disease typically do not need transfusion in the first decade of life. (See "Pathophysiology of thalassemia", section on 'Terminology and disease classification' and "Diagnosis of thalassemia (adults and children)", section on 'Epidemiology'.)

Management of the different types of thalassemia, including use of RBC transfusion, is discussed in greater detail separately. (See "Management of thalassemia", section on 'Management of anemia'.)

Autoimmune hemolytic anemia — Children with autoimmune hemolytic anemia (AIHA) may require RBC transfusion if the anemia is severe. Finding compatible RBC units to transfuse into a child with AIHA can be difficult and requires coordination with blood bank personnel. Transfusion can lead to additional hemolysis in patients with AIHA. However, it must be emphasized that transfusion therapy should not be withheld from a patient with life-threatening anemia. The patient's Hgb may not increase as expected due to hemolysis of transfused RBCs. Transfusion in patients with AIHA is discussed in greater detail separately. (See "Autoimmune hemolytic anemia (AIHA) in children: Treatment and outcome", section on 'Severe or life-threatening anemia'.)

Hypoproliferative anemia — Other chronic anemias that require RBC transfusion in children and infants include hypoproliferative anemias, such as Diamond-Blackfan anemia and aplastic anemia. (See "Diamond-Blackfan anemia", section on 'Transfusion therapy' and "Treatment of acquired aplastic anemia in children and adolescents".)

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

Weighing the benefits and risks – Transfusion of red blood cells (RBCs) can be lifesaving in patients with severe blood loss or severe chronic anemia. However, RBC transfusions have risks, including transfusion-associated circulatory overload, transfusion-related acute lung injury, transmission of infectious agents, fever, hives, and various immunologic consequences (including graft-versus-host disease). As a result, the benefits of transfusion must be carefully weighed against the potential adverse effects of the intervention. (See 'Introduction' above and "Red blood cell transfusion in infants and children: Administration and complications", section on 'Complications'.)

General indications – When deciding whether to transfuse, clinicians should not use the hemoglobin (Hgb) alone as the sole basis for decision-making. Other factors to consider include the acuity of anemia, degree of symptoms, hemodynamic stability, and the presence and nature of underlying conditions. (See 'Factors in clinical decision-making' above.)

Neonates – In neonates, common reasons for RBC transfusion include hemolytic disease of the fetus and newborn, perinatal blood loss, anemia of prematurity, and iatrogenic withdrawal of blood for laboratory testing. These issues are discussed separately. (See "Red blood cell (RBC) transfusions in the neonate".)

Unstable patients – Transfusion is often required for unstable anemic pediatric patients who have cardiopulmonary compromise (ie, patients with unstable shock and/or severe hypoxemia). In this setting, the need for transfusion is determined by clinical parameters rather than the patient's Hgb level, though transfusion is rarely indicated if the Hgb is >10 g/dL. (See "Shock in children in resource-abundant settings: Initial management", section on 'Fluid resuscitation' and "Septic shock in children in resource-abundant settings: Ongoing management after resuscitation", section on 'Blood transfusion'.)

Stable patients – For most hemodynamically stable hospitalized pediatric patients, including hemodynamically stable children with critical illness, we recommend a restrictive RBC transfusion strategy (ie, Hgb of 7 g/dL as the transfusion threshold) rather than more liberal strategies (Grade 1B). Exceptions to this include the six conditions listed below. (See 'Restrictive versus liberal strategy' above and 'Critical illness' above.)

Special circumstances – Separate criteria for transfusion may be used in the management of pediatric patients with the following conditions:

Trauma, if there is ongoing active bleeding (see "Trauma management: Approach to the unstable child", section on 'Blood products')

Surgery (see 'Surgery' above)

Malignancy (see 'Malignancy' above)

Cyanotic congenital heart disease (see 'Congenital heart disease surgery' above)

Chronic kidney disease (see "Chronic kidney disease in children: Complications", section on 'Anemia')

Chronic anemias, including (see 'Chronic anemias' above):

-Sickle cell disease (see "Red blood cell transfusion in sickle cell disease: Indications and transfusion techniques", section on 'Indications for transfusion')

-Thalassemia (see "Management of thalassemia", section on 'Management of anemia')

-Autoimmune hemolytic anemia (see "Autoimmune hemolytic anemia (AIHA) in children: Treatment and outcome", section on 'Severe or life-threatening anemia')

-Certain hypoproliferative anemias (eg, aplastic anemia, Diamond-Blackfan anemia, bone marrow failure syndromes) (see "Treatment of acquired aplastic anemia in children and adolescents", section on 'Supportive care' and "Diamond-Blackfan anemia", section on 'Transfusion therapy')

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Topic 5910 Version 36.0

References

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