Paediatric Transfusion Information

Excerpt from the Clinical Guidelines for the Use of Blood Products in South Africa, 5^th Edition (2014).

The field of transfusion medicine for children shares most of the same principles as that of adults, but it has distinctive features which need separate consideration. Those children who require blood products are also among the most intensively transfused of all patients. Because they are likely to have a long lifespan following transfusion, minimising adverse events is of great importance.

For the purpose of these guidelines, neonates are considered to be infants within 4 weeks of the normal gestational age (40 weeks) and infants are children within the first year of life.

INTRAUTERINE TRANSFUSION (IUT)

This should be done only by specialised units. It is most commonly indicated for correction of foetal anaemia caused by red cell allo-immunisation. Intra-uterine platelet transfusions are rarely indicated and are essentially used only to correct foetal thrombocytopenia caused by platelet allo-immunisation. However, the use of intravenous immunoglobulin in mothers with allo-immunisation has largely replaced foetal platelet transfusions.

Red cell products for intra-uterine transfusions are specially prepared by the blood transfusion service on request by the clinician. They are usually group O, Rh-D negative (preferably also Kell negative), crossmatch compatible with maternal serum, <5 days old, leucocyte depleted and irradiated.

NEONATAL TRANSFUSION 

Exchange Transfusion

Exchange transfusion may be used to manage severe anaemia at birth and to treat severe hyperbilirubinaemia, usually caused by haemolytic disease of the newborn (HDN). The aim in exchange transfusion is to remove Rh-D positive red cells, reduce bilirubin levels and remove maternally derived anti-D. The bilirubin level at which an exchange transfusion is indicated varies according to the weight and gestational age of the baby and the South African Neonatal Academic Hospitals’ Consensus Guidelines should be followed (S Afr Med J 2006; 96: 819-824). The early administration of intravenous immunoglobulin (1 g/kg) to Coombs positive infants with neonatal jaundice significantly reduces the level of exchange transfusions for hyperbilirubinaemia.

The red cell component used for exchange transfusion varies nationally and internationally. Some centres use unmodified whole blood while others plasma reduce whole blood to an Hct of 0.5 – 0.6 l/l.  Some centres, particularly in the USA, reconstitute RBC concentrates with fresh frozen plasma but it increases donor exposure and is not recommended unless whole blood is unavailable. The unit should be group O (or ABO compatible with maternal and neonatal plasma), Rh-D negative, crossmatch compatible with maternal and neonatal plasma, <5 days old, irradiated (must be transfused within 24 hours of irradiation) and leucocyte-depleted. An exchange of double the infant’s circulating blood volume is recommended: for pre-term infants 180-200 ml/kg, and for term infants 160-180 ml/kg should be transfused. For bigger infants where the calculated volume needed exceeds the amount in 1 unit of whole blood, then only one unit should be ordered initially. Serum bilirubin results post exchange transfusion will determine whether further blood is required. It should not be transfused directly from cold storage and should be warmed during the procedure with care taken to avoid overheating. In normal term infants the routine use of calcium gluconate is unnecessary. However, in sick, preterm neonates monitoring of ionised calcium is advisable.

Small Volume Red Cell Transfusion

Most neonatal transfusions are small volume (10-20 ml/kg). It should be noted that during the first 4 months of life, blood bank pre-transfusion testing differs from adults. If there are no clinically significant red cell antibodies in the infant or maternal plasma and the direct antiglobulin test is negative, a full crossmatch is not necessary, although the ABO and Rh-D group should be re confirmed prior to each subsequent transfusion.

Suggested transfusion thresholds for infants <4 months of age are listed below:

• Anaemia in the first 24 hours
  • Hb < 12g/dl
• Neonate receiving mechanical ventilation
  • Hb < 12g/dl
• Acute blood loss
  • > 10% blood volume lost
• Oxygen dependent (not ventilated)
  • Hb < 8-11g/dl
• Late anaemia, stable patient (off oxygen)
  • Hb < 7g/dl

The age of the unit does not matter for small volume top up transfusions, but large volume transfusions (exchange transfusion or acute blood loss) should be <5 days old in order to avoid hyperkalaemia and reduced 2,3 DPG levels with impaired oxygen release. Leucocyte depleted products are also recommended for infants (see Chapter 6).

Neonatal units should arrange with their blood banks that those neonates with extended transfusion needs are placed on a “limited donor exposure” programme where the transfusion requirements of one infant are met by reserving units bled from one donor for a specific infant. This minimises the infectious risk and red cell antigen exposure.

RED CELL TRANSFUSION IN OLDER CHILDREN (>1 YEAR)

Older children tolerate low Hb levels relatively well, unless there is accompanying respiratory or cardiac compromise. A Hb threshold of 7 g/dl is suggested, unless there is underlying severe cardiopulmonary disease, when the recommended threshold is 10-12 g/dl. As in adults, there is a tendency to more restrictive strategies, since recent studies have shown no significant increase in morbidity as a result. The recommended top-up transfusion dose for children is 10-20 ml/kg via a standard blood administration set or syringe with equivalent filtration. An initial dose of 15 ml/kg is ideal but as much as 20 ml/kg may be transfused in a haemodynamically stable patient if further transfusions are required. A 40 kg child receiving one standard red cell concentrate (± 300 ml) is receiving <10 ml/kg and therefore older children may require more than one unit, even with a restrictive strategy. Another approach is to use a formula:

Hb(target)-Hb(actual) x weight x transfusion factor (4 for RBC concentrates and 6 for whole blood). In normovolaemic patients furosemide (1 mg/kg) may be prescribed to prevent volume overload.

All infant and paediatric small volume RBC concentrates are leucocyte depleted, but in older children where adult RBC concentrates are used, a specific request must be made to for a leucocyte depleted product. The guidelines are given in Chapter 6, but bear repeating:

• Patients who have previously experienced febrile non-haemolytic febrile reactions
• Patients receiving multiple or lifelong transfusions
• Patients likely to receive organ or haemopoietic stem cell transplants
• Patients at high risk for CMV infection
• Critically ill patients and those who undergo cardiac surgery

If anaemia is accompanied by thrombocytopenia at a level requiring a platelet transfusion, fluid overload may result if platelets are rapidly transfused first.

The blood bank can usually issue group specific RBC concentrates within 20 minutes of receiving the cross-match request or immediately if the patient’s blood group has previously been documented. In the event of a dire emergency uncross-matched Group O blood can be given from the emergency fridge. Since Rh-D negative blood is usually in short supply, this should generally be reserved for females. Males can usually quite safely be given Group O Rh-D positive blood in emergency situations.

SPECIFIC COMPONENTS FOR NEONATES AND INFANTS

The use of an adult RBC concentrate, FFP or platelet concentrate for infants and small children would result in significant wastage given the volumes required. The blood services therefore prepare special products for paediatric use as follows:

• RBC concentrates: 25-150 ml
• FFP 100-160 ml
• Platelets: 50-60 ml; usually obtained from a single adult apheresis platelet unit which is split into a number of neonate/infant units.

PLATELET TRANSFUSION

Thrombocytopenia is common in sick pre-term infants and is associated with an increased risk of severe intra- and periventricular haemorrhage. Guideline thresholds for platelet transfusion are:

• Consider in all neonates at <30 x 10⁹/l
• Consider if increased bleeding risk <50 x 10⁹/l
  • <1 000 g and <1 week old
  • Clinically unstable (e.g. labile BP)
  • Previous major bleeding (e.g. grade 3-4 intraventricular haemorrhage)
  • Current minor bleeding
  • Coagulopathy
  • Planned surgery or exchange transfusion
• Major bleeding <100 x 10⁹/l

ABO group specific platelets are recommended. In neonatal alloimmune thrombocytopenia (NAITP), HPA-compatible platelets are required. In an emergency or when HPA typed platelets are unavailable, the use of maternal platelets is an option when the count is <30 x 10⁹/l.  Notwithstanding the threshold guidelines, the general principle should always be to treat the patient and not the platelet count. As far as possible platelet transfusions should be avoided for patients with immune thrombocytopenia unless there is life threatening haemorrhage or bleeding in critical areas while initiating therapies such as steroids and intravenous immunoglobulins. Platelets should not be given to patients with aplastic anaemia who are not bleeding for fear of generating platelet antibodies and rendering the patient refractory.

Dosage

Platelets for neonates are usually prepared from single donor apheresis procedures. In older children single donor apheresis units are generally reserved for those with severe pyrexial reactions, refractoriness and those being considered for stem cell transplantation.  A dose of 15-20 ml/kg is recommended and should be transfused using a platelet administration set. The platelets should be infused as rapidly as possible. If blood volume overload is a concern, furosemide (1 mg/kg) can be administered.

FRESH FROZEN PLASMA (FFP)

Indications for FFP in paediatric patients include:

• Neonates with a significant risk of bleeding (INR or APTT >1.5)
• Haemorrhagic disease of the newborn (while waiting for response to Vitamin K)
• Congenital coagulation deficiencies where a specific factor concentrate is not available or the deficient factor has not been identified

FFP is not recommended to treat sepsis, as a volume replacement fluid or to treat erythrocytosis/polycythaemia. No benefit has been shown for routine prophylactic use to treat PVH in pre-term infants.

ABO group specific plasma (or preferably AB plasma if available) is recommended. Group O FFP should not be given to neonates who are not group O unless the anti-A and -B titres have been screened for. A dose of 10-20 ml/kg is recommended administered via a standard blood administration set (170-200 μm filter) or via a syringe with equivalent filtration. As FFP is hyperosmolar, fluid overload is a risk in normovolaemic patients and close monitoring is advisable.

CRYOPRECIPITATE

Indicated for acquired (DIC most commonly) or congenital hypofibrinogenaemia. The threshold for transfusion is <1.5g/l depending on clinical circumstances (e.g. active bleeding, invasive procedure). Recommended dose is 5 ml/kg rapidly infused. It is dispensed as individual units each containing 10-15 ml and approximately 200 mg of fibrinogen.

TRANSFUSION IN NECROTISING ENTEROCOLITIS (NEC)

Infants with NEC may be infected with neuraminidase-producing organisms such as Clostridium sp. Neuraminidase can strip sialic acid residues from red cell sialoglycoproteins exposing the T-cryptantigen (T-activation).

T-activation can easily be detected by screening the affected red cells with a lectin (arachis hypogea). Adult plasma commonly contains anti-T, a potentially haemolytic IgM antibody. Although there have been published case reports of haemolysis following transfusion in neonates with NEC, detection of T-activation in these infants is not necessarily predictive for clinically significant haemolysis and there is a wide variation internationally in the policies adopted. It is, however, probably reasonable to provide components from donors who have low titre anti-T. Red cell concentrates contain minute volumes of plasma and the routine use of washed red cells in these patients is unnecessary.

ERYTHROPOIETIN

Healthy neonates commonly develop a “physiological anaemia” in the first few weeks after birth, with haemoglobin levels dropping to approximately 9 g/dl. Pre-term neonates and ill neonates may drop to even lower levels of 7-8 g/dl as a result of relatively ineffective production of erythropoietin plus loss of blood from frequent sampling for laboratory tests.

Although erythropoietin stimulates erythropoiesis in pre-term infants, elimination of or marked reduction in the need for red cell transfusions has not been demonstrated in clinical trials. Routine use of erythropoietin in neonates is not recommended.

IRRADIATION

The indications for irradiation are outlined in Chapter 7. Note that while irradiation is recommended prior to exchange transfusion, it should not be unduly delayed pending availability of an irradiated unit.

FURTHER READING

• Boulton F et al Transfusion guidelines for neonates and older children Brit J Haematol 2004; 124:433-453
• Simpson J Paediatric transfusion Vox Sanguinis 2001; 81: 1-5
• New H Paediatric transfusion Vox Sanguinis 2006; 90: 1-9
• Murray N Neonatal transfusion practice Arch Dis Child Fetal Neonatal Ed 2004: F101-F107
• Fabres J Estimating blood needs for very low birth weight infants Transfusion 2006; 46: 1915-1920
• Strauss R Controversies in the management of the anemia of prematurity using single-donor red cell transfusion and/or recombinant human erythropoietin Transf Med Rev 2006; 20: 34-44
• Josephson C Transfusion of neonates and pediatric patients In, Blood Banking and Transfusion Medicine – Basic Principles & Practice 2nd Edition, Hillyer C (Ed)
• Herman J (Ed) Pediatric Transfusion Therapy AABB Press 2002
• Murphy MF ref to Practical Transfusion Medicine
• Petz L Clinical Practice of Transfusion Medicine
• Harrison MC, Pillay S, Yoolay Y et al Resource implications of adopting a restrictive neonatal blood transfusion policy S Afr Med J 2013;103:916-917
• Roseff SD Pediatric Transfusion – A Physicians Handbook 2nd Edition AABB Press 2006
• Eder AF, Manno CS Does red cell T-activation matter? Brit J Haematol 2001; 114: 25-30