Clinical guidelines for use of red blood cells (RBC) in children are consensus rather than evidence based,³ with the latest National Health and Medical Research Council/Australian Society of Blood Transfusion Australian practice guidelines for blood product indication and administration available at www.nhmrc.gov.au, including haemoglobin (Hb) and platelet transfusion threshold triggers.¹ It is recommended that intravenous (IV) access be 22–24G or larger for children receiving blood products through a standard blood administration set primed with normal saline or the blood component. A blood warmer is indicated at flow rates >15 ml kg⁻¹ hr⁻¹ in children and for exchange transfusion in infants; very slow rates are recommended in small children if rapid volume expansion is not required. Blood products should not be warmed to above 41°C.⁴

The rate of administration should not be >5 mL min⁻¹ in the first 15 minutes as severe reactions are most likely to occur then; all blood components should be infused within 4 hours unless fluid overload is a risk. The child and infusion need to be monitored during blood product administration, more closely if unconscious or anaesthetised. A severe reaction requires suspension of blood product administration pending further incompatibility or bacterial contamination checks, consideration of antihistamines/steroids, and be reported to the Australian Incident Monitoring System in Australia or the New Zealand Blood Service.

Whole blood

Whole blood is rarely used, being specifically used for massive blood loss requiring simultaneous restoration of oxygen-carrying capacity and blood volume, haemorrhage with uncontrolled coagulopathy and exchange transfusion. Eight ml kg⁻¹ will increase a child’s haemoglobin concentration by 10 g/dL⁻¹, and administration must be completed within 4 hours to avoid bacterial contamination.

Packed red blood cells (PRBC)

Indications

The child’s Hb level, patient factors, signs and symptoms of hypoxia, ongoing blood loss, risk of anaemia and risk of transfusion should be considered. Each paediatric red cell unit is 25–100 mL (mean volume 50 mL) with a haemoglobin concentration of 100–150 g L^–1. PRBC is indicated if the oxygen-carrying capacity of blood is so reduced that the degree of anaemia poses a risk to the child or there is ongoing blood loss. Transfusion of PRBC in an asymptomatic child is not appropriate in most situations. PRBC transfusion is likely to be appropriate when haemoglobin is less than 70 g L^–1 in critically ill children.⁵ The haemoglobin threshold remains uncertain in stable children with anaemia. Use of PRBC with haemoglobin in the range 70–100 g L^–1 is appropriate if the child is at risk of hypoxia (cardiac, respiratory disease) and should be supported by the need to relieve clinical symptoms and signs. Criteria for PRBC in patients aged less than 4 months are different from those for older children. Infants in the former group have smaller blood volumes, decreased erythropoietin production (especially if premature) and there may be physiological anaemia of infancy.

Additional indications for PRBC include:

• emergency surgery in a child with significant preoperative anaemia;

• sickle cell disease with ischaemic organ events to suppress endogenous Hb production;

• Chronic congenital or acquired anaemia such as B-thalassaemia.

Administration

If stored in optimal conditions, RBC have a shelf life of 35–42 days. In haemorrhagic shock, RBC infusion at an initial volume of 10–20 mL kg^–1 should be considered when loss of blood volume approaches 30% (when hypotension first appears)³ and shock is refractory to non-blood fluid resuscitation. A single Hb level is not reliable in acute haemorrhage.³ If haemorrhage or haemolysis is accompanied by life-threatening hypoxia or rapid Hb decline then uncross-matched group O rhesus negative packed cells may be required. In less urgent cases, type-specific or cross-matched RBC is preferred. Rh type specific blood takes 15 minutes to cross match. If the child has no immediate need for RBC replacement and there is no ongoing bleeding or haemodynamic instability, cross-matched RBC may be administered over 4 hours. The volume required for elective top-up transfusion in mL is:

Weight(Kg) × haemoglobin rise required (gL ⁻¹)×3

Alternatives

Autologous blood (patient’s own blood is collected before surgery) is suitable for elective surgery but has no role in urgent situations. Perioperative blood scavenging may be useful in reducing exposure to donor blood. Red cell substitutes such as cell-free haemoglobins and perfluorocarbon emulsions require 100% oxygen to be effective and are still being trialled.

Adverse reactions

Fatal acute haemolytic reactions occur in 1:250 000–1:1 000 000 transfusions, with half caused by ABO incompatibility as a result of mismatching the blood with the patient or other administrative errors. Another 1:260 000 patients have a haemolytic reaction due to minor red-cell antigen incompatibility and 1:1000 patients experience delayed haemolytic reactions.

Platelets

Indications

Platelets are appropriate in bleeding children in whom thrombocytopenia is a major contributory factor. In haemorrhagic shock, platelet infusion should be considered in massive transfusion associated with platelet count less than 50 × 10⁹ L^–1. Platelet transfusion may be appropriate in children with failure of platelet production and platelet count less than 10 × 10⁹ L^–1, as there is a risk of intracerebral bleeding. Platelets may be given prophylactically in children undergoing invasive procedures or surgery, to maintain platelet count >50 × 10⁹ L^–1. In children with platelet dysfunction (inherited or acquired), platelets are administered to treat active bleeding. Platelets are indicated in thrombocytopenic premature infants with active bleeding or prior to an invasive procedure.

Administration

Each paediatric unit is 40–70 mL and contains at least 5.5 × 10¹⁰ platelets.

Infusion of 5–10 mL kg^–1 of platelets will lead to a rise in platelet count of 50–100 × 10⁹ L^–1.

Adverse reactions and other problems

Platelets are stored at room temperature to maintain their ability to aggregate, and this promotes bacterial growth. Compared with other blood components, the risk of bacterial contamination of platelets is relatively high at 1:2000 units and sepsis is the most frequent severe complication of platelet use. Platelets older than 5 days lose their ability to aggregate and are therefore less effective. Alloimmunisation due to the development of platelet alloantibodies from repeated transfusions may lead to refractory thrombocytopenia.

Fresh frozen plasma (FFP)

FFP contains all coagulation factors, except VII, including approximately 150 units of factor VIII. FFP is used to treat bleeding related to coagulopathy associated with cardiac surgery or massive transfusion for haemorrhagic shock when 50% or more of circulating blood volume has been replaced. FFP may be considered for treatment of acute disseminated intravascular coagulation (DIC) and thrombotic thrombocytopenic purpura (TTP). Less urgent indications include children with coagulopathy undergoing invasive procedures/surgery, liver disease-related coagulopathy, replacement of single coagulation factor deficiency where a specific factor concentrate is not available, and reversal of life-threatening bleeding due to warfarin. FFP should not be used for volume expansion, plasma-exchange procedures or treatment of immunodeficiency states. Specific recombinant coagulation factors rather than FFP are used to treat specific inherited coagulation disorders.

Administration

In life-threatening exsanguination requiring massive transfusion, FFP may be required to minimise dilutional coagulopathy. One unit of FFP is required for every four units of packed cells but titrate FFP use against the coagulation profile if possible. FFP contains all coagulation factors including approximately one unit of factors VIII and V for each mL of FFP. FFP is administered at an initial dose of 10–20 mL kg^–1 from a 50 mL paediatric bag. This dose raises coagulation factor level by 20% immediately.³ After thawing, FFP needs to be used immediately or stored at 2–6°C for up to 24 hours.

Cryoprecipitate

Cryoprecipitate is appropriate to use when clinical or potential bleeding (invasive procedure, trauma or DIC) is attributable to fibrinogen deficiency.³ It contains factors VIII, XIII, fibrinogen, von Willebrand’s factor and fibronectin. Approximately 200 units of each of these factors are contained in a 15 mL bag. This allows more rapid administration than FFP, whilst reducing the risk of fluid overload. In infants, a dose of 10–15 mL is sufficient to achieve haemostasis. Cryoprecipitate is not used to treat von Willebrand’s disease, haemophilia and deficiencies of factor XIII or fibronectin.

Clotting factor concentrates

Bleeding or thrombosis in children with proven coagulation or antithrombotic factor deficiency may require specific factor replacement. These factors have become safer with the advent of synthesis using recombinant genetic technology. Recombinant factor VIII concentrate is used to treat haemophilia A whereas recombinant factor IX is the treatment of choice for haemophilia B. Antithrombin III, protein S and protein C concentrates are used to treat patients with these specific factor deficiencies.

Albumin

Indications

Albumin is derived from volunteer human plasma pools and is indicated for rapid volume expansion in children with evidence of shock or poor perfusion. In paediatric emergency practice, albumin may be used in the initial fluid resuscitation for hypovolaemic shock, although it is no better than crystalloids or other colloids in this setting in adults.³ Other indications include the treatment of hypoproteinaemia, diuretic-resistant nephrotic syndrome, large volume paracentesis, severe burns after the first 24 hours and plasma exchange. There is no evidence for albumin use as a nutritional supplement or for the treatment of ascites or oedema related to portal hypertension.

Administration

Albumin 4% (40 g L^–1) at 10–20 mL kg^–1 is used for volume expansion. Albumin 20% (200 g L^–1) is used for plasma albumin repletion on a gram-for-gram basis.

Adverse effects and risks

There is evidence that albumin is associated with increased mortality and morbidity in critically-ill adults,⁶ but no such evidence in young children. Complications of albumin use include circulatory and sodium overload, with the relative risk of viral disease transmission being less compared with cellular blood components.

Normal human immunoglobulin (NIGH)

Human immunoglobulin affords passive immunity against many infectious agents for several weeks. NIGH is derived by Cohn fractionation from pooled plasma and contains antibodies to viruses that are prevalent in the general population. Subclasses are present in the approximate proportions G1 60%, G2 30%, G3 6% and G4 4% but there is no such thing as generic IgG. The ‘new’ purified commercial products are all a little different, with different minor reaction rates. NIGH is administered IM for pre- or post-exposure prophylaxis against measles, varicella zoster and hepatitis A. IV NIGH (either Intragam or Sandoglobulin) is used to treat idiopathic thrombocytopenic purpura (ITP), Kawasaki’s disease, perinatal acquired immune deficiency syndrome, Guillain–Barré syndrome, demyelinating disease, immunological disorders associated with antibody deficiency (such as primary hypogammaglobulinaemia) and sepsis with secondary immunodeficiency. Allergic reactions and, rarely, anaphylaxis may occur. NIGH is contraindicated in children with selective IgA deficiency and evidence for its role in the treatment and prevention of neonatal sepsis is conflicting. Immune response to live virus vaccines (with the exception of yellow fever vaccine) may be inhibited by NIGH given 3 weeks before or 3 months after immunisation.

Hyperimmune immunoglobulins (IG)

Maternal administration of Rhesus (Rh) Ig prevents the development of Rh antibodies in a Rh-negative mother who gives birth to a Rh-positive baby. This reduces the risk of maternal Rh sensitisation and maternal-neonatal Rh-incompatibility in subsequent pregnancies. Cytomegalovirus (CMV) Ig is used in the prevention and treatment of CMV in children at risk of adverse sequelae from CMV infection, such as with immunodeficiency and following renal and bone-marrow transplantation. Zoster Ig (ZIG) is advisable within 72 hours after varicella exposure in children with cellular immune deficiency, immunosuppression, neonates whose mothers are susceptible to primary varicella infection and infants who are less than 28 weeks’ gestation at birth. Infants born to HbsAg-positive mothers should receive hepatitis B Ig and commence primary hepatitis B vaccination within 12 hours of birth. Respiratory syncytial virus (RSV) Ig is used prophylactically in infants at high risk of severe RSV infection, including those with bronchopulmonary dysplasia. Tetanus Ig passively protects non-tetanus immune children who sustain a tetanus-prone wound and a tetanus Ig infusion is used to treat clinical disease.

Risks of blood component use

These are categorised as acute or delayed, haemolytic or non-haemolytic, allergy-based or not. Mild non-haemolytic febrile reactions can occur with any blood component and need to be distinguished from major reactions. If a major reaction occurs, the transfusion is discontinued and threats to the airway, breathing and circulation are attended to. Specific treatment for anaphylaxis, sepsis and blood group incompatibility may be required, in consultation with a haematologist. Recipient and donor blood samples are sent for immunological and microbiological testing. Critical adverse incidents should be notified to the blood bank and followed up as a quality assurance activity with appropriate adjustments made to hospital transfusion protocols to reduce risk of recurrence.

Infections

Even though blood components are the safest they have ever been, infection transmission risk remains emotive and highly publicised, especially for human immunodeficiency virus (HIV).⁷ Infection acquired from a blood component is a rare occurrence when compared with non-infectious complications. The estimated risks per actual blood unit transfused are 1:200 000–1:2 000 000 for HIV, 1:30 000–1:250 000 for hepatitis B and 1:30 000–1:150 000 for hepatitis C. Disease transmission occurs primarily during the window period when a blood donor is infectious and the infection is immunologically silent and therefore undetectable on screening tests. Other infectious agents encountered include hepatitis A and G, human T lymphotropic virus 1 (HTLV I) and II, parvovirus B19, syphilis, malaria, babesiosis, Salmonella and Trypanosoma cruzi. There is no current evidence to suggest that variant Creutzfeldt–Jakob disease can be transmitted by blood transfusion. Donor selection and exclusion, donated blood screening, post-collection leucodepletion and viral inactivation help to minimise risk of infection transmission. Using pooled blood components allows contamination of the entire pool from one infectious donor and is therefore less safe than components derived from a single donor. Bacterial contamination of blood components, either from prolonged/faulty storage or acquired from the donor, is most frequently due to occult donor bacteraemia and donor skin organisms. Yersinia enterocolitica and other Gram negatives are most frequently implicated.