14. RBC transfusion in pediatrics

Key points

• Blood transfusions are critical interventions for pediatric patients, but they carry risks of morbidity and mortality.
• Patient Blood Management (PBM) in pediatrics remains underutilized, often due to limited data and variability in clinical practices, even though individualized assessment of transfusion needs is essential.
• Guidelines stress the importance of a restrictive transfusion strategy; evidence indicates that lower hemoglobin thresholds are effective in hemodynamically stable children, yet many clinicians continue to transfuse based on higher thresholds.
• Alternatives to transfusion, such as pharmacological agents, iron supplementation, and blood conservation techniques during surgery, are vital in minimizing the need for blood transfusions in children.
• Enhancing transfusion safety involves adherence to protocols, educational initiatives for healthcare providers, implementation of safety checklists, and continuous monitoring of transfusion-related incidents to improve patient outcomes.

Introduction

Blood transfusions are often lifesaving widespread interventions offered to the pediatric age group of patients admitted to the hospital. However, blood transfusion has also been associated with mortality and morbidity (lung injury, volume overload and immunomodulation) (1).  As per the WHO report (2) up to 54% of blood transfusions are given to children under the age of 5 years in low-income countries (LIC), making pediatric transfusions a significant part of the clinical blood requirement in present times. Apart from the nonavailability of blood in LIC, even inappropriate use of red cell transfusions is also a growing concern. With very limited data and high variations in clinical practice, patient blood management (PBM) in the pediatric patient population is not commonly practiced. 

Hemoglobin is one of the most important critical factors considered for the decision for transfusions. However, in assessing the need or indication of transfusion in a pediatric patient with anemia, the following issues should also be addressed (3). 

1. The general state of health and well-being or criticality of the illness
2. Nutritional status as iron deficiency is still the most common cause of anemia in children
3. Hemodynamic stability
4. The likely timeframe for the development of anemia (acute/ subacute/ chronic)
5. The etiology (is correction possible with treatment other than transfusion?)
6. Comorbidity
7. Symptoms and signs suggesting a compensated or uncompensated state of anemia
8. History of bleeding (uncontrolled or ongoing) and extent of blood loss
9. Planned management of the patient (invasive procedure requiring general anesthesia and risk of blood loss)

Indications and thresholds in pediatric red blood cell transfusion

Red blood cell (RBC) transfusion aims to improve oxygen delivery and oxygen consumption. TRIPICU study by Lacroix et al. (4) showed that a lower threshold of hemoglobin (restrictive strategy) in hemodynamically stable critically ill children was as efficacious as the liberal transfusion strategy. Despite the evidence that a restrictive transfusion strategy is non-inferior and reduces donor exposure by minimizing the transfusion needs, many physicians still practice transfusing kids on a higher hemoglobin threshold. Following are the guidelines for transfusion of children more than 4 months of age (5). 

1. An emergency surgical procedure in a patient with significant postoperative anemia
2. Preoperative anemia when other corrective therapy is not available
3. Intraoperative blood loss >15% of total blood volume
4. Hematocrit <24% and
   1. In the perioperative period, with signs and symptoms of anemia
   2. While on chemotherapy / radiotherapy
   3. Chronic congenital or acquired symptomatic anemia
5. Acute blood loss with hypovolemia not responding to other therapy
6. Hematocrit <40%
   1. With severe pulmonary disease
   2. On extracorporeal membrane oxygenation (ECMO)
7. Sickle cell disease (simple or exchange transfusion)
   1. Cerebrovascular accident
   2. Acute chest syndrome
   3. Splenic sequestration
   4. Aplastic anemia
   5. Recurrent priapism
   6. Preoperative administration when general anesthesia is planned
8. Chronic transfusion programs for disorders of red cells production (for eg. thalassemia)

Restrictive and liberal transfusion strategies

A group of pediatric critical care physicians published a detailed guideline for RBC transfusion in critically ill pediatric patients. The guidelines were referred to as “Transfusion and Anemia Expertise Initiative” (TAXI) recommendations for transfusion in critically ill children (6). The group further emphasized the need to evaluate the risks and benefits of red cell transfusions. As part of the TAXI guidelines high GRADE evidence supports the use of restrictive RBC transfusion practices, although more studies are warranted. As per TAXI, transfusion should be considered based on hemoglobin level as follows (6).

1. A hemoglobin of less than 5 g/dl should always be considered as the threshold for RBC transfusions (except in allo or autoimmune hemolytic anemia).
2. Hemoglobin between 5-7g/dl requires more studies for evidence generation (under various scenarios) to assess the risks and benefits of blood transfusion.
3. With haemoglobin above 7g/dl, there are very few conditions in which transfusion is recommended in a hemodynamically stable child.

Patient Blood Management (PBM) in pediatrics is a comprehensive approach aimed at optimizing the care of pediatric patients who require blood transfusions. This strategy emphasizes the minimization of unnecessary transfusions, thereby mitigating the associated risks and improving patient outcomes. A critical component of PBM is the implementation of single unit transfusions (SUT), which have been shown to significantly reduce the incidence of transfusion-related complications, such as transfusion-related acute lung injury (TRALI) and transfusion-associated immunomodulation (TRIM). Given the lower blood volume in pediatric patients, the judicious use of SUT can effectively manage anemia while preserving the blood supply and minimizing exposure to potential adverse effects from multiple transfusions. The application of PBM principles in pediatrics not only enhances patient safety but also aligns with the broader objectives of evidence-based transfusion practices (7–9).

Alternative to transfusion

Considering the unique physiological characteristics of children, minimising or avoiding transfusions is essential in transfusion medicine due to the potential risks involved. These risks include both infectious and non-infectious complications, with non-infectious reactions accounting for a significant majority of severe or fatal outcomes (10). Minimising blood loss, applying a restrictive transfusion strategy including SUT practice, individualised assessment of transfusion indication, use of pharmacological agents, as well as surgical and anesthetic interventions, play a vital role in avoiding unnecessary transfusions (11).  A few alternatives to avoid transfusion include:

A, The ability to tolerate anemia:

The ability to tolerate anemia is crucial, as it guides individualized treatment strategies and helps avoid unnecessary interventions. Children with chronic anemia may adapt over time, exhibiting fewer symptoms than those with acute anemia, influencing the urgency and type of treatment required.

B, The use of pharmacological agents to treat anemia, provided the cause has been investigated (12).
a. Iron Supplementation: Iron deficiency is the most common cause of anemia in children. Oral iron supplements are the standard treatment, effectively increasing hemoglobin levels and replenishing iron stores. In cases of severe deficiency or malabsorption, intravenous iron may be considered.
b. Vitamin B12 and Folate Supplementation: Deficiencies in vitamin B12 or folate can lead to megaloblastic anemia. Supplementing these vitamins corrects the deficiency and normalizes red blood cell production.
c. Erythropoiesis-Stimulating Agents (ESAs): For anemia associated with chronic kidney disease or certain chronic illnesses, ESAs like erythropoietin can stimulate red blood cell production. However, their use in children requires careful consideration due to potential risks and limited pediatric-specific data.

The use of pharmacological agents to manage bleeding should be considered based on the underlying condition and current guidelines, such as (13,14).

1)    Antifibrinolytic Agents such as Tranexamic Acid (TXA) and Epsilon Aminocaproic Acid (EACA)
2)    Vasopressin and Analogues Desmopressin Acetate (DDAVP)
3)    Coagulation Factor Concentrates
4)    Vitamin K (Phytomenadione)
5)    Prothrombin Complex Concentrate (PCC)
6)    Human Fibrinogen Concentrate
7)     Recombinant Factor XIII

The use of blood conservation techniques during pediatric surgery plays a crucial role, as it may minimize the need for transfusions. Miniaturized cardiopulmonary bypass (CPB) circuits, modified ultrafiltration (MUF), and intraoperative blood salvage adapted for children reduce the chance of transfusion exposure (15).

The use of point-of-care devices to promptly assess coagulation, such as thromboelastography (TEG) and thromboelastometry (ROTEM), allows better management of bleeding risks (16,17). Trials involving point-of-care devices in pediatric populations are warranted.

Transfusion Safety in Pediatrics

Blood transfusion is a vital, life-saving procedure frequently performed in hospital settings. However, children possess unique physiological and biochemical characteristics that differ from those of adults, potentially affecting their reactions to transfusions. Notably, research indicates that pediatric patients experience transfusion reactions at rates twice as high as those observed in adults (18–20). According to the SHOT report 2023, the total number of pediatric cases has increased slightly compared to 2022, and clinical and laboratory errors remain common and need to be addressed (21). Ensuring transfusion safety in pediatric patients is essential to minimize risks and enhance clinical outcomes. Recent studies have identified several key areas for improvement:

1. Adherence to Transfusion Protocols: A study conducted in Brazil analyzed 234 transfusions in 90 pediatric patients and found discrepancies between prescribed and administered volumes, as well as timing issues. These inconsistencies highlight the need for strict adherence to transfusion protocols to prevent potential adverse events (22).
2. Educational Initiatives for Healthcare Providers: Enhancing the knowledge of healthcare professionals, particularly pediatricians, regarding transfusion safety is crucial. An educational intervention study demonstrated significant improvements in transfusion safety knowledge among pediatricians post-training, suggesting that targeted education can lead to safer transfusion practices (23).
3. Implementation of Safety Checklists: Utilizing safety checklists during transfusion procedures can serve as a valuable tool to ensure compliance with safety protocols. These checklists help in systematically verifying patient identification, blood product compatibility, and monitoring for adverse reactions, thereby reducing the likelihood of errors (24).
4. Continuous Monitoring and Reporting: Establishing a culture of continuous monitoring and reporting of transfusion-related incidents is vital. Encouraging healthcare providers to document and report adverse events and near-misses facilitates the identification of areas needing improvement and supports the development of strategies to enhance transfusion safety.

Incorporating these measures—strict adherence to protocols, targeted education, utilization of safety checklists, and fostering a culture of monitoring and reporting—can significantly improve transfusion safety in pediatric care, ensuring better outcomes for young patients.