Neonatal transfusion

10.2: Neonatal transfusion

Neonates are defined as infants up to 28 days after birth. Most neonatal transfusions are carried out
in low birth weight preterm infants treated on neonatal intensive care units (NICUs). Transfusion
triggers in neonates are controversial and mainly based on expert clinical opinion, although recent
randomised controlled trials of ‘liberal’ versus ‘restrictive’ red cell transfusion policies in very low birth
weight preterm babies are starting to influence clinical guidelines.

10.2.1: Neonatal red cell exchange transfusion

Neonatal red cell exchange transfusion is mainly used in the treatment of severe hyperbilirubinaemia
or anaemia in babies with HDFN. It removes antibody-coated neonatal red cells and reduces the
level of plasma unconjugated bilirubin (the cause of bilirubin encephalopathy). The steep decline in
the incidence of HDFN following the introduction of maternal anti-D Ig prophylaxis, more effective
antenatal monitoring and treatment, and the use of intensive phototherapy and intravenous
immunoglobulin postnatally has made red cell exchange transfusion an uncommon procedure that
should only be performed in specialist units by experienced staff. A ‘double volume exchange’ (160–
200 mL/kg) removes around 90% of neonatal red cells and 50% of bilirubin.

The Blood Services produce a special red cell component for neonatal exchange transfusion (Table
10.3). It is ordered in specially by hospitals when required and close collaboration between the
clinical team, hospital transfusion laboratory and blood service is essential. The component should
be warmed to 37°C immediately before transfusion. It should be irradiated if this requirement does
not cause clinically important delay in provision (irradiation is essential if the baby has received IUT).

Table 10.3 Red cells for neonatal exchange transfusion

Plasma reduced with haematocrit of 0.5–0.6 (NHSBT 0.5–0.55) to reduce the risk of
post-exchange polycythaemia

In CPD anticoagulant

Less than 5 days old

Irradiated (essential if previous IUT)

CMV negative

Sickle screen negative

Usually produced as group O (with low-titre haemolysins)

RhD negative (or RhD identical with neonate) and Kell negative

Red cell antigen negative for maternal alloantibodies

IAT crossmatch compatible with maternal plasma

10.2.2: Large volume neonatal red cell transfusion
Large-volume transfusion, equivalent to a single circulating blood volume (approximately 80 mL/kg),
is mainly used in neonatal cardiac surgery. The component supplied (mean unit volume 294 mL) is
in SAG-M anticoagulant (see Chapter 3) and has the same specification as that used for neonatal
‘top-up’ transfusions. It should be transfused less than 5 days from donation to reduce the risk of
hyperkalaemia. Irradiated blood is required in babies with known or suspected T-cell
immunodeficiency, such as DiGeorge syndrome, in which case the blood should be transfused
within 24 hours of irradiation.

10.2.3: Neonatal ‘top-up’ transfusion

Repeated small-volume ‘top-up’ red cell transfusions (up to 20 mL/kg) are commonly carried out in
preterm babies, mainly to replace losses from repeated blood testing exacerbated by reduced red
cell production (‘anaemia of prematurity’). Up to 80% of preterm babies weighing less than 1500 g at
birth are transfused at least once. Indications for transfusion in this group have largely been based
on the Hb concentration combined with the cardiorespiratory status of the baby (e.g. requirement for
oxygen or ventilatory support) and factors such as weight gain, although the evidence base is weak.
The new British Committee for Standards in Haematology (BCSH) Transfusion Guidelines for
Neonates and Older Children(http://www.bcshguidelines.com) suggest the transfusion thresholds
summarised in Table 10.4.

Table 10.4 Summary of BCSH recommendations for neonatal top-up transfusions

Suggested transfusion threshold

Postnatal Hb (g/L)
age On Off
Ventilated
oxygen/CPAP oxygen
First 24 hours <120 <120 <100
≤Week 1 (days 1–7) <120 <100 <100
Week 2 (days 8–14) <95
<75–85 depending
≥Week 3 (day 15 <100
<85 on clinical situation
onwards)

Several randomised controlled trials have addressed the risks and benefits of liberal or restrictive red
cell transfusion policies in very low birth weight infants. A systematic review by the Cochrane
Collaboration in 2011 found a modest reduction in exposure to transfusion in the restrictive
transfusion groups and no significant difference in mortality, major morbidities or survival without
major morbidity. The approximate lower limits used to define a ‘restrictive’ transfusion policy in these
trials are shown in Table 10.5. Although many experts now favour a restrictive transfusion policy
(Venkatesh et al., 2013), it is important to note the Cochrane Review comment that ‘the safe lower
limits for haemoglobintransfusion thresholds remain undefined, and there is still uncertainty
regarding the benefits of maintaining a higher level’. Further large clinical trials are advocated,
especially to address the issues of longer term (including neurodevelopmental) outcomes and cost-
effectiveness. Most local guidelines are closer to the restrictive thresholds used in the trials.

Table 10.5 Approximate capillary Hb transfusion thresholds used for ‘restrictive’ transfusion
policies in studies evaluated by the Cochrane Review

Postnatal Respiratory No respiratory

age support support
Week 1 115 g/L 100 g/L
Week 2 100 g/L 85 g/L
Week 3 85 g/L 75 g/L

Many neonatal red cell transfusions are given to replace losses from frequent blood sampling. This
can be reduced by avoiding non-essential tests, using low-volume sample tubes, validated near
patient testing, micro-techniques in the laboratory, and non-invasive monitoring where possible.
Donor exposure can also be reduced by allocating single donor units, split into ‘paedipacks’, to
babies predicted to need more than one transfusion episode within the expiry date of the donation.
This requires close collaboration between the clinical team and blood transfusion laboratory.

The specifications for neonatal/infant small-volume red cells for transfusion are shown in Table 10.6.
The typical transfusion volume is 10–20 mL/kg (higher end of dose for severe anaemia or bleeding)
administered at 5 mL/kg/h. Top-up transfusions in excess of 
20 mL/kg are not recommended because of the risk of transfusion-associated circulatory overload
(TACO).

During the first 4 months of life ABO antigens may be poorly expressed on red cells and the
corresponding ABO antibodies may not have yet developed (making confirmation by ‘reverse
grouping’ unreliable). Maternal IgG ABO antibodies may be detected in neonatal plasma. Wherever
possible, samples from both the mother and infant should be tested for ABO and RhD grouping, an
antibody screen should be performed on the larger maternal sample, and a direct antiglobulin test
(DAT) on the infant’s sample. Because of the significant risk of ‘wrong blood in tube’ errors due to
misidentification, the infant’s blood group should be verified on two separate samples (one of which
can be a cord blood sample) as recommended for adult patients, providing this does not delay the
emergency issue of blood. If there are no atypical maternal antibodies and the infant’s DAT is
negative, top-up transfusions can be given without further testing during the first 4 months of life.
Details of pretransfusion testing in neonates and infants are given in the 2013 BCSH guidelines for
pre-transfusion compatibility procedures in blood transfusion laboratories
(http://www.bcshguidelines.com). Irradiated neonatal components are indicated if the infant has
previously received IUT or has a proven or suspected T-cell immunodeficiency disorder.

Table 10.6 Red cells for small-volume transfusion of neonates and infants

Haematocrit 0.5–0.7

In SAG-M anticoagulant/additive solution (approximately 20 mL residual plasma)

Up to 35 days from donation

Group O (or ABO-compatible with baby and mother) and RhD negative (or RhD compatible with
the neonate)

In practice, many hospitals use O RhD negative

CMV seronegative for neonates

10.2.4: Neonatal platelet transfusions

Severe thrombocytopenia (<50×10 9/L) is a common finding in infants treated on NICUs, especially in
sick preterm neonates (NAIT is discussed in section 10.1). There is no clear correlation between the
severity of thrombocytopenia and major bleeding, such as intraventricular haemorrhage, suggesting
other clinical factors are important. Audits show that, contrary to many published guidelines, the
majority of platelet transfusions are given as ‘prophylaxis’ in the absence of bleeding. A randomised
trial is comparing transfusion thresholds of 25 and 50x109/L. Meanwhile, an example of suggested
transfusion thresholds is given in Table 10.7. Single donor apheresis platelets manufactured to
neonatal specifications are used. They should be CMV-negative and ABO RhD identical or
compatible with the recipient. A typical dose is 10–20 mL/kg.

Table 10.7 Suggested transfusion thresholds for neonatal prophylactic platelet transfusion
(excluding NAIT)

Platelets <20 or
In the absence of bleeding
30×10 /L
9

Bleeding, current coagulopathy, planned surgery or

Platelets <50×10 /L9

exchange transfusion
Platelets <100×10 /L 9
Major bleeding, major surgery (e.g. neurosurgery)

10.2.5: Neonatal FFP and cryoprecipitate transfusion

Normal neonates have different, age-related values for common coagulation screening tests
compared to older children and adults. This complicates the diagnosis of ‘coagulopathy’. At birth,
vitamin-K-dependent clotting factors are 40–50% of adult levels and are lowest in preterm infants.
The prothrombin time (PT), thrombin time (TT) and activated partial thromboplastin time (APTT) may
be longer, although overall haemostatic function may be normal. In addition, most laboratories rely
on published neonatal reference ranges, which may differ from those using local analysers and
reagents. Disseminated intravascular coagulation (DIC) is common in sick neonates and
haemorrhagic disease of the newborn due to vitamin K deficiency may cause major bleeding in
babies who have not received appropriate vitamin K prophylaxis at birth.

Sick neonates in intensive care are commonly transfused with fresh frozen plasma (FFP), which
carries a significant risk of serious acute transfusion reactions (see Chapter 5). The 2009 National
Comparative Audit of the use of FFP
(http://hospital.blood.co.uk/safe_use/clinical_audit/national_comparative/index.asp) confirmed that,
contrary to published guidelines, 42% of FFP transfusions to infants were given ‘prophylactically’ in
the absence of bleeding, on the basis of abnormal clotting tests. BCSH guidelines recommend that
FFP should be used for:
  Vitamin K deficiency with bleeding
 DIC with bleeding
 Congenital coagulation factor deficiencies where no factor concentrate is available (Factor V
deficiency)

The dose of FFP is usually 12–15 mL/kg. The degree of correction is unpredictable and clotting tests
should be repeated after administration.

FFP should not be used as routine prophylaxis against peri/intraventricular haemorrhage in preterm
neonates (evidence from a randomised controlled trial), as a volume replacement solution, or just to
correct abnormalities of the clotting screen.

Cryoprecipitate is used as a more concentrated source of fibrinogen than FFP and is primarily
indicated when the fibrinogen level is <0.8–1.0 g/L in the presence of bleeding from acquired or
congenital hypofibrinogenaemia. The usual dose is 5–10 mL/kg.

FFP for neonates (and all patients born on or after 1 January 1996) is imported from countries with a
low risk of vCJD and is pathogen-inactivated. Methylene blue inactivation is used by the UK Blood
Services and commercial pooled solvent detergent treated FFP is also available. It should be ABO
identical with the recipient or group AB (group O FFP should only be given to neonates of group O).

10.2.6: Neonatal granulocyte transfusion

There is no conclusive evidence from randomised controlled trials to support the use of granulocyte
transfusions in neutropenic, septic neonates. Current guidelines do not recommend their routine use
in the absence of further prospective studies.

10.2.7: T-antigen activation

Occasional severe haemolytic reactions have been reported in neonates or infants receiving blood
or FFP containing anti-T antibodies. The T-antigen may be exposed on the surface of neonatal red
cells by neuraminidase-producing bacteria such as Clostridium spp., often in association with
necrotising enterocolitis (NEC). As T-antigen activation is often found in healthy neonates and
severe haemolysis is very rare, the need to screen neonates with NEC and make special
components available remains controversial and is not performed in many countries. Red cells in
SAG-M, containing only small amounts of plasma, are regarded as safe. All non-essential
transfusions of FFP and platelets should be avoided. If low-titre anti-T components are regarded as
essential, platelets in platelet suspension medium can be used and methylene blue treated FFP with
a low titre of anti-T may be available from the Blood Services.