Pediatric Transfusion Medicine

A variety of neonatal and pediatric patients require blood component transfusions. This chapter focuses on aspects of blood-bank laboratory testing, blood products and components, transfusion indications, and potential adverse events that are specifically relevant to neonates and children.

Pediatric Blood Banking

Blood and Blood Components

Several different blood components, including whole blood, reconstituted whole blood, red blood cells (RBCs), platelets, plasma, and cryoprecipitated antihemophilic factor (CRYO) may be available from a blood bank for transfusion. Recently, additional components have become available in the United States. They are photochemically treated INTERCEPT platelets and plasma, and solvent detergent–treated plasma, Octaplas. The availability of specific component types varies between blood suppliers.

Whole blood is infrequently used and may not be available from a particular blood bank or blood supplier, but it may be available on request and is used by some pediatric cardiac surgery services. Whole blood contains all RBCs, plasma, platelets, and an anticoagulant-preservative solution containing citrate, phosphate, dextrose, and possibly adenine.
RBC units mostly contain RBCs but also contain some plasma and a preservative solution. Most RBC units contain an additive preservative solution that includes some combination of adenine, dextrose, and mannitol. Additive solutions are safe for relatively small (≤20 mL/kg) transfusions. There are concerns over the safety of these additives given in large transfusions to neonates, and their safety in this setting has never been proven in a randomized clinical trial. In view of this concern, some hospital blood banks provide nonadditive RBC units or wash additive units intended for large transfusions to neonates. Because many blood centers provide only additive RBC units to hospital blood banks and washing an RBC unit takes approximately 1 hour, blood banks have been unable to supply RBC units without additives in many situations. Thus, many institutions now have significant experience transfusing large volumes of additive RBC units to neonates and have not noticed any problems.
Two general types of platelet units are available in the United States, although any one blood bank or hospital may stock only one of these types. These two types, whole blood–derived platelets (platelets) and platelets collected by apheresis (pheresis platelets), differ in their size. A platelet unit contains approximately 5.5 to 10 × 10 ¹⁰ platelets in about 50 mL, whereas a pheresis platelet unit contains at least 3 × 10 ¹¹ platelets in about 200 mL. It is often easier to use platelet units for small children because pheresis platelets usually need to be aliquoted to provide the correct dose. However, many blood centers exclusively provide only one type of platelet component. Recently, two modifications of platelet components were approved in the United States, although these had been in use in other countries for several years.
- Platelets that have undergone pathogen inactivation using the INTERCEPT Blood System (Cerus Corporation, Concord, CA) that mixes amotosalen HCl, a synthetic psoralen compound that intercalates with nucleic acid and, on activation with ultraviolet (UV) light, cross-links pathogen and white blood cell DNA, inhibiting replication. Almost all of the amotosalen, a potential carcinogen, is removed during processing. However, INTERCEPT platelets are contraindicated for neonatal patients treated with phototherapy devices emitting wavelengths <425 nm due to potential erythema from interaction between UV light and amotosalen. Fortunately, phototherapy devices currently used in the United States emit higher wavelength light in the 430 to 490 nm range.
- Platelets stored in a platelet additive solution (PAS). PAS platelets contain very little plasma, reducing the risk of allergic reactions and transfusion-related acute lung injury (TRALI) but also lowering the dose of coagulation factors contained in the platelet component.
Plasma is frozen to retain functional plasma proteins including clotting factors. Depending on the timing of freezing and thawing, the component may be called fresh frozen plasma (FFP) or another name. However, all of these plasma components contain all the necessary clotting factors. Two pathogen-inactivated plasma products that had been available in several countries are now available in the United States:
- INTERCEPT (Cerus Corporation, Concord, CA) treated plasma using the same system as described above.
- Octaplas (Octapharma, Hoboken, NJ) is a filtered pooled plasma product that is subjected to solvent/detergent treatment to inactivate lipid-enveloped viruses. Its safety and efficacy in pediatric patients have not been evaluated, which would be important in neonates whose coagulation system regulation differs from adults. Specifically, Octaplas contains low concentrations of protein S and α2-antiplasmin, two inhibitors of the coagulation system that are present in low concentrations in neonates.
Cryoprecipitate is prepared from plasma and contains high concentrations of fibrinogen.
Because pediatric patients require smaller doses of blood components, they often require only a portion of a component.
RBCs are stored refrigerated and hence can be prepared in aliquots as needed if the blood bank has the necessary equipment. Alternatively, the blood center can collect RBC units into a collection system in which additional bags are attached for dispensing aliquots. Whole blood is also stored refrigerated, but its use is limited and it is almost never prepared in aliquots.
All platelet components are stored at room temperature under constant agitation and can be prepared in aliquots when needed in the blood bank if the blood bank has the necessary equipment and supplies. However, 1 unit of whole blood–derived platelets does not contain many doses, even for infants, and most blood banks do not aliquot them.
All plasma products are stored frozen and are not generally aliquoted after thawing. However, many blood centers will prepare plasma aliquots before freezing.
Because even small infants rarely require less than 1 unit of cryoprecipitate, this component is rarely prepared in aliquots.

Directed Donations

Families sometimes prefer to donate blood for their children using a process known as directed donations, and some blood banks permit this. If this is done without medical reason, it offers no benefit and there are potential risks. Although directed donors need to go through the same screening and infectious disease testing process as all allogeneic blood donors, some studies suggest that directed donors have a slightly higher risk for infectious disease transmission.

In addition, directed donors may be a poor choice for immunologic reasons. For example, if a neonate has alloimmune thrombocytopenia or anemia, the pathologic antibody is a passively acquired maternal antibody directed against inherited paternal antigens. In this case, blood donated by the father would be recognized by the antibody in the baby’s circulation and cleared just as the neonate’s own platelets or erythrocytes are cleared. Another example in which immune concerns make directed donors a poor choice involves transplants. Some patients may require a future tissue or bone marrow transplant, and blood relatives often serve as the best donors for such transplants. However, prior transfusions from relatives may sensitize the patient’s immune system to antigens present on the tissues of blood relatives, complicating those potential tissue or bone marrow transplants.

Technical Considerations/Mechanical Devices

Smaller pediatric patients require small transfusions administered at slow rates. Aliquots of components often need to be prepared. This can be performed by collecting blood into collection bags interconnected with sterile tubes or by attaching additional containers to a standard blood component by using a sterile docking device that produces a sterile weld between two separate tubing sets.

Blood components must be filtered to remove microaggregates before transfusion. For an adult patient, this is normally accomplished by transfusing the component through a filter contained within the blood administration set. These standard blood administration sets are not ideal for transfusing small patients because 20 to 40 mL of the component is lost in the dead space of the administration set. Pediatric microaggregate filters with much smaller dead space are available.

For nonbleeding patients, blood components should be transfused at a rate of no more than 5 mL/kg/h. For infants, this corresponds to a lower rate than can be regulated by most standard infusion pumps. Hence, these transfusions are usually performed using syringe pumps, with the blood component aliquot transferred to a syringe prior to the transfusion. Often, the blood bank prepares aliquots of a blood component through a pediatric microaggregate filter directly into a syringe, eliminating the need for bedside microaggregate filtration.

Transfusion Medicine: General Indications and Dosing

Indications for Red Blood Cells Transfusion in Neonates, Children, and Adolescents

Neonates Less Than 4 Months Old

RBC transfusions are more commonly administered to hospitalized neonates than any other pediatric patient age group, and RBCs are the component most often transfused in this population. Symptomatic anemia is the major indication for simple transfusion, and an RBC transfusion should be considered when the venous hemoglobin is less than 10 to 13 g/dL depending on the patient’s clinical condition or when a neonate has lost approximately 10% of his/her blood volume. A transfusion dose of 10 to 15 mL/kg of RBCs should yield an increase in the neonate of 2 to 3 g/dL of hemoglobin after transfusion.

Two randomized clinical trials of premature infants in neonatal intensive care units, examining restrictive versus liberal RBC transfusion practices, had conflicting results. Therefore, most guidelines have been based on experience rather than evidence-based medicine ( Table 119.1 ). A retrospective review investigating preoperative blood transfusions (PBTs) in surgical neonates revealed that when using a propensity score-matched model, PBTs are independently associated with increased morbidity and mortality, acknowledging that prospective studies are still needed. Notably, previous data surrounding the contribution of RBC transfusion and anemia to necrotizing enterocolitis in very low birth weight (VLBW, ≦1500 g) infants has been inconsistent. However, a secondary, prospective, multicenter observational study has shown that it is severe anemia, and not transfusions themselves, that is the associated risk factor for necrotizing enterocolitis. An ongoing study ( http://clinicaltrials.gov/01702805 ) has the promise of providing definitive evidence to inform RBC transfusion practice in this population.

Table 119.1

Guidelines for Transfusion of Red Blood Cells in Infants Less Than 4 Months of Age

1.
Hematocrit <20% with low reticulocyte count and symptomatic anemia (tachycardia, tachypnea, poor feeding)
2.
Hematocrit <30% and
- a.
  On <35% oxygen hood, or
- b.
  On oxygen by nasal cannula, or
- c.
  On continuous positive airway pressure and/or intermittent mandatory ventilation on mechanical ventilation with mean airway pressure <6 cm of water, or
- d.
  With significant tachycardia or tachypnea (heart rate >180 beats/min for 24 h or respiratory rate >80 breaths/min for 24 h)
- e.
  With significant apnea or bradycardia (more than six episodes in 12 h or two episodes in 24 h requiring bag and mask ventilation while receiving therapeutic doses of methylxanthines), or
- f.
  With slow weight gain (<10 g/day observed over 4 days while receiving >100 kcal/kg/day)
3.
Hematocrit <35% and
- a.
  On >35% oxygen hood, or
- b.
  On continuous positive airway pressure/intermittent mandatory ventilation with mean airway pressure >6–8 cm of water
4.
Hematocrit <45% and
- a.
  On extracorporeal membrane oxygenation (ECMO), or
- b.
  With congenital cyanotic heart disease

RBC , Red blood cell.

With respect to blood product age, one prospective randomized clinical trial found equivalent clinical outcomes in neonates transfused with fresh RBCs stored for less than 7 days when compared to those transfused with standard-issue RBCs with a mean age of 14.6 days, although some have criticized the generalizability of the study results.

Older Infants, Children, and Adolescents

RBC transfusion indications for infants older than 4 months and for young children are similar to those of adults. However, there are several noteworthy differences between children and adults: total blood volume, ability to tolerate blood loss, and age-specific hemoglobin levels ( Table 119.2 ). In infants, RBC transfusions are primarily given for surgical losses, anemia of chronic diseases, and malignancies. Infants inherently have lower hemoglobin levels than adults and remain asymptomatic at lower hemoglobin concentrations, especially if the anemia occurs gradually. Even with these physiologic differences, general transfusion-trigger guidelines for pediatric intensive care unit patients are similar to those for adults, with a transfusion trigger of 7 g/dL of hemoglobin for hemodynamically stable patients being shown to be safe for these patients. This threshold has also been found to be safe for hematopoietic progenitor cell (HPC) transplant patients. In pediatric intensive care unit patients, consensus has arrived at a strong recommendation to transfuse when hemoglobin drops to below 5 g/dL; however, at higher hemoglobin levels, there is less agreement regarding RBC transfusion practices. The usual dose of RBCs is 10 to 15 mL/kg.

Table 119.2

Guidelines for Transfusion of Red Blood Cells in Patients More Than 4 Months of Age

1.
Emergency surgical procedure in patient with significant postoperative anemia
2.
Preoperative anemia when other corrective therapy is not available
3.
Intraoperative blood loss ≥15% total blood volume
4.
Hematocrit <21%–24%
- a.
  In perioperative period, with signs and symptoms of anemia
- b.
  While on chemotherapy/radiotherapy
- c.
  Chronic congenital or acquired symptomatic anemia
5.
Hematocrit <21%, hemodynamically stable patients >3 days old in the pediatric intensive care unit
6.
Acute blood loss with hypovolemia not responsive to other therapy
7.
Hematocrit <40% and
- a.
  With severe pulmonary disease
- b.
  On ECMO
8.
Sickle cell disease (may require exchange transfusion)
- a.
  Cerebrovascular accident
- b.
  Acute chest syndrome
- c.
  Splenic sequestration
- d.
  Aplastic crisis
- e.
  Recurrent priapism
- f.
  Preoperatively when general anesthesia is planned (target hemoglobin 10 mg/dL)
9.
Chronic transfusion programs for disorders of RBC production (e.g., β-thalassemia major and Diamond-Blackfan syndrome unresponsive to therapy)

ECMO , Extracorporeal membrane oxygenation; RBC , red blood cell.

There is no evidence that pediatric patients benefit from transfusion of RBCs of a particular age. A multicenter, blinded, randomized clinical trial showed that among critically ill pediatric patients, fresh RBCs did not reduce the incidence of new or progressive multiple organ dysfunction syndrome (including mortality) when compared to the use of standard-issue RBCs.

Platelets

Platelet transfusion support in pediatric patients is usually intended as a prophylactic strategy to prevent bleeding ( Table 119.3 ). In sharp contrast to adults, who rarely develop spontaneous severe bleeding until their platelet counts fall below 10,000/μL, preterm infants with other complicating illnesses may bleed at higher platelet counts. The increased risk may be secondary to (1) lower levels of plasma coagulation factors, (2) natural anticoagulants that potentiate thrombin inhibition, (3) intrinsic or extrinsic platelet dysfunction, and (4) increased vascular fragility. Platelet counts and function in older children are similar to those of adults, and the indications for platelet transfusions do not differ from the indications for adults. The prophylactic platelet transfusion thresholds in premature infants have historically been quite controversial and based primarily on expert consensus rather than evidence-based medicine. However, a new multicenter randomized trial supports using a platelet-count threshold of 25,000/μL to guide the administration of prophylactic platelet transfusions in premature neonates who are not bleeding. In this study, it was shown that premature infants randomly assigned to receive prophylactic platelet transfusions at a threshold of 50,000/μL had a significantly higher rate of death or major bleeding event.

Table 119.3

Guidelines for Transfusion of Platelets in Neonates and Older Children

Modified from Roseff SD, Luban NLC, Manno CS. Guidelines for assessing appropriateness of pediatric transfusion. Transfusion . 2002;42:1398; and Wong CC, Luban NLC. Intrauterine, neonatal, and pediatric transfusion. In: Mintz PD, ed. Transfusion Therapy: Clinical Principles and Practice . 2nd ed. Bethesda, MD: AABB Press; 2005:159.

Platelet Count <150,000/μL

1.
Platelet count 5000–10,000/μL with failure of platelet production
2.
Platelet count <25,000–30,000/μL in neonate with failure of platelet production
3.
Platelet count <25,000–50,000/μL in stable premature infant
- a.
  With active bleeding, or
- b.
  Before an invasive procedure with failure of platelet production
4.
Platelet count <50,000–100,000/μL in sick premature infant
- a.
  With active bleeding, or
- b.
  Before an invasive procedure in patient with DIC

Without Thrombocytopenia

1.
Active bleeding with qualitative platelet defect
2.
Unexplained excessive bleeding during cardiopulmonary bypass
3.
Patient receiving ECMO with
- a.
  Platelet count <50,000–100,000/μL
- b.
  Higher platelet counts and bleeding

DIC , Disseminated intravascular coagulation; ECMO , extracorporeal membrane oxygenation.

You're Reading a Preview

Become a Clinical Tree membership for Full access and enjoy Unlimited articles

Become membership

If you are a member. Log in here