Chapter 34
Blood Component Therapy in Children and Neonates
Anne Kelly1, Simon J. Stanworth2,3 and Helen V. New4
1 Department of Haematology, Division of Transfusion Medicine, University of Cambridge/NHS Blood and Transplant Cambridge, Cambridge, UK
2 NHS Blood and Transplant/Oxford University Hospitals NHS Trust, John Radcliffe Hospital, Oxford, UK
3 Department of Haematology, University of Oxford, Oxford, UK
4 Department of Paediatrics, Imperial College Healthcare NHS Trust/NHS Blood and Transplant, London, UK
Introduction
The paediatric population receiving blood transfusions in critical care comprises two main groups of recipients: neonates and patients admitted to paediatric intensive care. The age and weight ranges of recipients are therefore very broad, from babies less than 400 g and 25 weeks gestation, to adolescents weighing over 100 kg. As for all interventions in paediatric practice, blood transfusion has risks alongside perceived benefits, and the balance between these factors may vary across the wide differences in physiology, co-morbidities and reasons for admission from preterm neonates up to ‘small’ adults.
Traditionally, the evidence supporting transfusion recommendations in neonatal and paediatric intensive care has been patchy and in some cases derived from adult practice. No one would now doubt the limitations of extrapolating from adult to neonatal medicine and the need for specialist transfusion input into paediatric and neonatal issues. Specific clinical studies in these patient groups are now starting to emerge, which will attempt to provide more rational recommendations for practice. In this chapter, we will discuss key aspects of transfusion in paediatric and neonatal critical care including the risks, special transfusion requirements, specific indications and the volumes to prescribe.
Risks of transfusion
Transfusion has played a core role as part of the supportive therapy for sick neonates and children and enabled the survival of increasingly premature neonates and sick children. But blood for transfusion is not without risk, as well as being a costly and scarce resource. Important information on adverse outcomes of transfusion is available from national haemovigilance schemes such as the UK Serious Hazards of Transfusion (SHOT) reporting scheme, although it is difficult to accurately assess the prevalence of these outcomes. Over the last few years, a specific chapter in the SHOT annual report has been devoted to neonatal and paediatric issues. Key points relevant to paediatric transfusion practice from the SHOT and other data include:
- There have been a disproportionate number of reports from patients less than 18 years by comparison to reports in adults [1] and moreover from transfused neonates when compared to children.
- In the most recent SHOT report [2], 35/122 (29%) of paediatric reports were in infants (babies under 1 year of age), of whom 15/35 (43%) were neonates less than 4 weeks old.
- A significant proportion of all reports in children and neonates were related to transfusion errors, including transfusion of an incorrect blood component.
- Common errors are in the correct identification of neonates and children, potentially due to lack of name bands or moving cots in neonatal units, as well as errors in the selection and administration of blood components.
- There are repeated reports of over-transfusion of children as the result of prescribing transfusions as ‘units’. It is therefore recommended that paediatric transfusions are prescribed in mL and that the rate or length of time of the transfusion is specified [3].
- In recent years, there has been an increase in the number of reports to SHOT of paediatric acute transfusion reactions, including anaphylactic reactions, probably due to a change in reporting patterns.
- Other risks may be more common in small neonates receiving large volume transfusions, e.g. metabolic effects such as hyperkalaemia.
- There are limited data from neonates on other potentially serious complications of transfusion, such as transfusion-associated lung injury (TRALI) and transfusion-associated circulatory overload (TACO), these being generally better defined and recognized in critically ill adults.
- The incidence of transfusion transmission of infections, in particular viral infections, is (reassuringly) very low, but it is important that clinicians are aware of the possibility of transmission of bacterial infections particularly from platelet components, which are stored at room temperature and therefore are an excellent ‘broth’ for culture.
- Blood transfusions may cause fluid overload, and routine transfusion volumes as mL/kg body weight are often higher in neonates when compared to average adults. There is some evidence for persistent echocardiographic abnormalities in anaemic infants following a transfusion.
It is important to emphasize that blood for transfusion is a biological agent with potential immunomodulatory effects. There may be additional unrecognized risks from transfusion in critically ill neonates and children, which are not well captured by current definitions of transfusion adverse outcomes. Unrecognized immunomodulatory effects could be manifested by small but nevertheless clinically significant increased rates of infection in critical care or complications such as necrotizing enterocolitis (NEC). However, evidence for causal relationships between transfusion and such outcomes is currently lacking.
The reason for transfusion should be discussed with parents and documented, although formal written consent is not a requirement in many hospitals.
Special requirements
Given the potential for full life expectancy in transfused neonates and sick children who are discharged home, a number of additional safety measures have been introduced in the UK and other countries to further reduce the already low risks of transfusion transmission of pathogens. For example, donations for children and neonates are collected from donors who have been screened and tested for microbiological infections on multiple occasions, to minimize any risks that collection of blood from donors occurs during a ‘window period’ of an infection. There have been four confirmed cases of transmission of the prion disease variant CJD (vCJD) through blood transfusion in the UK. To minimize risks of transfusion transmission of vCJD, in addition to universal leukcodepletion of blood components for all recipients, plasma and cryoprecipitate for children and neonates are currently sourced from the either Austria or the USA where the population rates of vCJD are essentially zero.
Additional clinical special requirements may be required for specific groups of recipients. When this is the case, the requirements should be notified to the blood transfusion laboratory and included as part of the transfusion prescription and administration checks.
Irradiated cellular components
Several groups of patients are immunologically at risk of transfusion-associated graft-versus-host disease (TA-GVHD) if transfused with cellular components, which contain functionally active T lymphocytes. In order to remove this risk, the components are irradiated, reducing the shelf life of red cells to 14 days (24 h for red cells for neonatal exchange and large volume transfusions) due to increased leakage of potassium. Patient groups requiring irradiated components who may be admitted to either paediatric or neonatal intensive care units (PICUs or NICUs) include those undergoing stem cell transplantation (until T-cell recovery or discontinuation of GVHD prophylaxis), with Hodgkin’s disease or T-cell immunodeficiencies, taking certain drugs (purine analogues, alemtuzumab) and receiving post-intrauterine transfusions (for 6 months post delivery) and neonatal exchange transfusions where possible (see [4] for further details). On PICU, it is important to consider the need for irradiated components for patients undergoing cardiac surgery who could have DiGeorge’s syndrome and associated T-cell immunodeficiency.
Cytomegalovirus (CMV) negative components
Patients who are immunodeficient and naïve to cytomegalovirus (CMV) infection are at risk of disseminated CMV. Leukcodepletion has, however, vastly reduced the risk of CMV transmission via component transfusion. Recent recommendations from the Advisory Committee on the Safety of Blood, Tissues and Organs (SaBTO) reduced the number of patient groups who should receive CMV seronegative components to foetuses, neonates up to 28 days post expected delivery date, seronegative pregnant women undergoing elective transfusions and recipients of granulocyte transfusions. Leukcodepletion alone is considered adequate for stem cell transplant patients, organ transplant patients and those with immunodeficiency (inherited or acquired).
HLA-matched platelets
Not infrequently, concerns arise as to the effectiveness of platelet transfusion, triggered by poor or poorly sustained count increments. Causes of platelet refractoriness can be divided into non-immunological and immunological, due to anti-HLA antibodies. Non-immunological causes are more common, including sepsis and medications such as antifungals. However, if these non-immune factors are excluded, then a screen for human leukcocyte antigen (HLA) antibodies should be sent and platelets, which are matched for the patient’s HLA type, may be requested. It is important to monitor platelet increments post transfusion of HLA-matched platelets in order to identify the most effective donors for each individual recipient.
Transfusions in paediatric critical care
Red cells
Indications for transfusion and transfusion triggers
Decisions about whether or not to transfuse red cells require consideration of the balance between maintenance of adequate haemoglobin (Hb) to ensure tissue oxygenation and limitation of unnecessary red cell transfusion. There are two main categories of indication for red cell transfusion in children: either in the setting of acute blood loss to restore circulating blood volume or, more usually, to restore Hb levels above a certain threshold. Measures to reduce the need for transfusion include optimization of iron status prior to surgery, cell salvage during major surgery and minimizing iatrogenic blood loss from frequent blood sampling of inpatients.
