The primary goal of transfusion medicine is to provide the safest blood transfusions possible for patients who need them. In the pediatric patient population, red blood cell (RBC) transfusions comprise the majority of transfusions (58.5%), followed by platelet and plasma transfusions (26% and 15.4%, respectively).¹

While pediatric patients received 2.6% of the 15 million red cell units and 2.3% of the 4.5 million plasma units transfused annually, the most recent available National Blood Collection and Utilization Survey reports that there was a 7.6% increase in RBC transfusions in the pediatric population, which is in contrast to the declining trends identified in the adult patient population.¹ In addition, the overall trends for platelet transfusions indicate an increase, as well as for other blood derivatives, such as intravenous immunoglobulin (IVIG).

Recognition of the clinical benefits of hemotherapy should help guide the clinician in the decision to transfuse. These benefits must be weighed against adverse events associated with transfusion, including infections, as well as cost. A British report indicated that the most common error (80% of errors) in pediatrics is transfusion of the incorrect blood component.² In this report, a blood component was considered to be incorrect if it did not meet special requirements, if there was an administrative error, or when there was a laboratory error. Examples included not transfusing a cytomegalovirus (CMV)-negative or irradiated unit when required by hospital policy, transfusing one twin with an RBC unit intended for the other, or not considering maternal anti-erythrocyte antibodies when selecting an RBC unit for a neonate. An understanding of pediatric-specific issues may help minimize such problems.

Transfusional requirements and parameters may differ between children and adults, especially in neonates and young children. Most studies focus on adults with extrapolation of these data and guidelines to children. Children have slightly higher blood volume per kilogram (of ideal body weight) than adults. Term neonates have 85 mL/kg, while preterm neonates have 100 mL/kg. Children up to pre-adolescence have 75 to 85 mL/kg and adolescents have 70 to 75 mL/kg. Neonates are at risk for anemia due to phlebotomy and a poor erythropoietic response. Neonatal organ functions are not fully developed and may lead to metabolic and electrolyte imbalances following transfusion. Small-volume and slow-rate transfusions may prevent such problems. With more rapid transfusions, particular attention should be given to hypocalcemia due to citrate present in blood components as well as hyperkalemia. Neonates, especially premature infants, are also at risk for hypothermia and its attendant problems, such as acidosis and hypoxia.³ The use of blood warmers may be useful for more rapid transfusions in susceptible neonates.

In most instances, medical consent should be obtained from the parents and/or legal guardians of all children requiring blood transfusions.⁴ Institution-specific policies may also require obtaining assent from certain minors who have some decision-making capacity. The exception is when blood transfusion is deemed immediately life-saving and a parent/legal guardian is unable to provide consent. The patient should be examined prior to transfusion. This provides a baseline for assessing patients for any transfusion reactions.

Whole blood transfusion is rarely performed, and is not available in most institutions.⁵ However, blood banks can prepare reconstituted whole blood by mixing RBCs with plasma. Reconstituted whole blood is usually used for neonatal exchange transfusions for hyperbilirubinemia or severe anemia.

Specific blood components are transfused depending on therapeutic goals. Blood components can be divided into the traditional whole blood components (i.e. packed red blood cells, platelets, granulocytes, plasma, and cryoprecipitate) as well as derivatives (i.e. intravenous immunoglobulin, factor concentrates). Blood is considered a biological product, with manufacturing regulated by the US Food and Drug Administration. Each blood component must be collected and stored under specific conditions, which limits their shelf life.

PACKED RED BLOOD CELLS

There are two ways of determining the dose for packed red blood cell (pRBC) transfusion. The standard dose is 10 to 15 mL/kg body weight. At this dose, RBC transfusion is expected to increase the hemoglobin by 2 to 3 g/dL.⁶ The following formula can be used to estimate the volume of pRBCs needed to increase the hemoglobin by a desired amount:

Packed red blood cell transfusions are performed to increase oxygen carrying capacity,^8,9 with the ultimate goal of adequate tissue oxygenation.¹⁰

Patients with acute blood loss can have impaired oxygenation due to both intravascular fluid loss with resultant cardiac output compromise and oxygen carrying capacity loss (i.e. loss of RBC mass). In severe blood loss, the primary consideration should be volume resuscitation, usually with crystalloid, to avoid cardiovascular collapse. The clinical presentation should guide the amount of pRBCs to transfuse. In infants less than 4 months of age, acute anemia can result in signs such as tachypnea and tachycardia. Transfusion rates are relatively rapid in order to correct volume loss and counteract volume loss.

In contrast, patients suffering from chronic anemia may have compensated by increasing oxygen extraction and cardiac output. Such patients include those with hemoglobinopathies and other intrinsic erythrocyte disorders. In addition, patients with nutritional deficiency (e.g. iron, vitamin B, or folate deficiency) or intoxication (e.g. lead poisoning) can also present with chronic anemia. In these cases, the etiology of the anemia should be corrected. Transfusions should be reserved until symptomatic anemia is present or there is imminent risk of decompensation. Red cell transfusions should be carried out slowly (rate of 1–2 mL/kg/hr) because these patients are at risk for cardiopulmonary overload.

In emergencies, there may be insufficient time to type, screen, and/or cross-match blood. The patient should be given blood group O, Rh-negative red cells and AB plasma while the blood bank completes the workup.

Preoperative blood transfusions may be indicated because of the dangers of general anesthesia in the setting of very low hemoglobin values. In adults and children, RBC transfusion is generally indicated before anesthesia when the hemoglobin is below 6 to 8 g/dL.¹¹ Children with congenital cardiac disease are often transfused at higher triggers to achieve a hemoglobin concentration of up to 13 g/dL.³ Clinical judgment should be used, taking into consideration the patient’s overall health, hemodynamics, and nature of the procedure^12-14 when deciding to provide preoperative transfusions.

Most patients with sickle cell disease do not require regular transfusions; however, some patients receive chronic transfusions to decrease recurrent sickle pain crises, acute chest syndrome, or stroke.^15,16 Chronic red cell therapy may be offered as simple transfusions or as exchange transfusions, and its goal generally is to maintain hemoglobin S at <30% to 50% while keeping the hematocrit close to 30% to avoid hyperviscosity.¹⁶ Preoperatively, maintaining the hemoglobin of sickle cell patients at 10 g/dL, irrespective of hemoglobin S fraction, is associated with a 50% reduction in transfusion-associated complications. This strategy has the same clinical outcomes as a more aggressive transfusion strategy to keep the hemoglobin S fraction to <30%.¹⁷ The 10-g/dL hemoglobin threshold for preoperative transfusion was also shown to decrease the occurrence of perioperative acute chest syndrome in low- and moderate-risk surgeries when compared with a preoperative hemoglobin below 10 g/dL.¹⁸

In patients with autoimmune hemolytic anemia, transfusion of compatible blood is difficult because of anti–red blood cell antibodies present against universal red cell antigens that confound cross-matching. In an otherwise healthy child in whom anemia has developed slowly, without cardiovascular disease or hypoperfusion, a hemoglobin >4 g/dL appears sufficient for oxygenation.¹⁹ If the patient does require transfusion, the RBCs will often be incompatible and the patient should be monitored closely for transfusion reactions (Table 93-1).

Additional considerations for red cell transfusions should be made when dealing with premature and low-birth-weight neonates. RBC transfusion should be considered in newborns, preterm, and low-birth-weight infants when there is shock or >10% blood volume loss or when the degree of anemia leads to growth failure, spells, or other clinical complication.²⁰ Hemoglobin should be maintained at 13 g/dL (~45% hematocrit) in such patients with cardiovascular disease (including congenital heart disease) and 8 to 10 g/dL (~30% hematocrit) in patients with tachypnea, tachycardia, or recurrent apnea.^3,20 While the Premature Infants in Need of Transfusion (PINT) study showed that in very low birth weight (VLBW) infants (<1000 g), a low-threshold hemoglobin sliding scale trigger was not any worse than liberal transfusion, other studies and a subsequent review of the PINT data suggested that a higher hemoglobin level in VLBW infants may improve neurocognitive development and leads to decreased costs of care related to neurologic function.^21-23

PLATELETS

Platelets are prepared from whole collections or from an apheresis platelet collection. One whole blood–derived platelet is a sufficient dose for most patients up to 10 to 15 kg. Larger patients can receive pools of whole blood–derived platelets in which the pool size is proportional to the size of the patient. One apheresis platelet is usually an adequate dose for most adult patients, and aliquots can be prepared for smaller pediatric patients. Platelets must be kept at 20 to 24^°C with gentle agitation. Platelets only have a 5-day shelf life. The standard dose is ~5 mL/kg. At this dose, the platelet count should increase 50,000/μL.⁶

Platelet transfusions are indicated in patients who are bleeding due to thrombocytopenia or platelet dysfunction. Thrombocytopenia may be due to decreased production or increased clearance/consumption of platelets. Platelet dysfunction may be due to congenital causes (e.g. Bernard-Soulier syndrome) or an acquired dysfunction (e.g. uremic thrombocytopathy). In general, transfused platelets will be more lasting and beneficial when the underlying reason for thrombocytopenia is one of defective production. In cases of increased platelet clearance, for example in primary autoimmune thrombocytopenia (ITP) or consumptive coagulopathy, platelet transfusions are generally reserved for life- or limb-threatening bleeding. In such cases, definitive therapy involves correction of the underlying pathology.

Prophylactic platelet transfusions in non-bleeding, thrombocytopenic patients may also be considered if they are at risk for bleeding. There is no particular platelet count known at which bleeding will occur. In at-risk patients, however, it has been shown that hemorrhage is more frequent and more severe, the lower the platelet count.²⁴ Though there are limited data on platelet count thresholds for prophylactic transfusions in pediatric patients, the American Society for Clinical Oncology guidelines²⁵ have nonetheless been extended to the pediatric population.²⁶ A general transfusion guideline for prophylactic platelet transfusion includes a platelet count of <10,000/μL and <50,000/μL prior to an invasive procedure. Institutional guidelines should be followed.

Pediatric patients are generally transfused with ABO-compatible platelets whenever possible.¹⁸ Because platelets have ABO antigens, incompatibility results in slightly diminished half-life; however, this is not usually clinically significant.^16,27 Conversely, anti-A antibodies present in the plasma of platelets from group O and B blood donors can causes clinically significant hemolysis of patient A or AB erythrocytes. This rare complication appears to be more prevalent in pediatric patients, and the risk may be mitigated by blood bank policies preventing transfusions of platelets with high titers of incompatible anti-A antibodies.²⁸

Current methods for preparation of platelet units by apheresis or from pooled whole blood results in less than 0.007 mL or 0.5 mL of contaminating RBCs, respectively.²⁹ The risk of RhD alloimmunization in RhD-negative individuals is low following transfusion with either RhD-positive pooled³⁰ or single donor^31,32 platelet units. RhD allosensitization appears to be dose dependent, but doses as low as 0.03 mL have resulted in RhD allosensitization.³³ Consequently, anti-RhD immunoglobulin may be offered to RhD-negative females with child bearing potential within 72 hours of receiving RhD-positive platelets, but institutional policies may vary.

Occasionally, patients will exhibit unresponsiveness to platelet transfusions (i.e. platelet refractoriness) by failing to increase their platelet count after transfusion. There are many causes of refractoriness and up to a quarter of those are due to anti-human leukocyte antigen (HLA) alloantibodies.³⁴ A platelet count taken 10 to 60 minutes after platelet transfusion is helpful in documenting unresponsiveness. Platelet-refractory patients may benefit from transfusion of HLA-matched or HLA-compatible platelets when the etiology is due to HLA alloantibodies.^35-37

PLASMA

Several different types of plasma products are available. The distinguishing feature is the time between collection and a certain storage condition, and how long after thawing the plasma can be used. This determines the stability of coagulation factors. The most commonly used product is fresh frozen plasma (FFP). FFP is plasma that is frozen within 8 hours of collection. Prior to transfusion, FFP is thawed at 37^°C and can be kept refrigerated for up to 24 hours. Other plasma products can be frozen up to 24 hours following collection and/or kept refrigerated for up to 5 days following thawing. The standard dose for plasma transfusion is 10 to 15 mL/kg with an expected 15% to 20% increase in factor levels.⁶

Plasma transfusion is indicated for multiple plasma factor replacement or as an alternative for single factor replacement when a purified or recombinant factor is not available.^30,38 Patients with liver disease, vitamin K deficiency, or treatment with vitamin K antagonists (e.g. warfarin) may cause multiple coagulation factor deficiency. In addition, patients undergoing massive transfusion should also receive plasma transfusions³⁹ for dilutional coagulopathy as well as disseminated intravascular coagulation (DIC). Plasma should be used judiciously, since unwarranted plasma transfusions increase risk of transfusion reactions. The recommended dose of FFP is 10 to 20 mL/kg body weight for pediatric patients,³⁸ but must be used cautiously to avoid fluid overload.