Transfusion
Introduction
Incidence
Risk
Factors
Consequences
Diagnosis
Treatment
Key
Points
References
Introduction.
Simple red cell transfusions are most commonly used to correct acute blood loss and hypovolaemia in
preterm and term neonates, as well as the correction of anaemia of prematurity. Exchange transfusions
may be used to correct severe anaemia, and to treat hyperbilirubinaemia and polycythaemia. This policy is
directed at practices used to avoid red cell transfusions, criteria for red cell transfusion and the practicalities
of red cell transfusion.
Incidence
All infants admitted to JSN between 1996 to 1998 that were born < 27 weeks gestation required red cell
transfusions, with the median number of transfusions per infant ranging from 7 at 24 weeks to 4 at 26
weeks gestation. Transfusion requirements decrease substantially after 26 weeks and are uncommon after
29 weeks gestation.
Table 1: Median number of red cell transfusions by gestational age at birth:
Gestation: (weeks)
24
25
26
27
28
29
30
Red cell transfusions (median)
7
4
4
1
1
0
0
Figure1: Incidence simple red cell transfusion by gestation in
surviving preterm neonates admitted to JSN between 1996 to 1998:
Risk factors
Anaemia in the neonate may result from:
1. Peripartum: blood loss foetal-maternal haemorrhage
vasa praevia
tight nuchal cord
occasionally with antepartum haemorrhage and
placental abruption
2. Early Iatrogenic blood loss from frequent blood sampling, and
3. Intermediate: Anaemia of prematurity resulting from 1
Rapid rate of body growth
Short red blood cell survival
Reduced erythropoietin production in preterm infants
4. Late (post discharge):
anaemia of prematurity (due to iron deficiency 2 )
Isoimmunisation (most commonly rhesus)
Normal haemoglobin levels in neonates 3, 4
Table 2:
Age
GA / birth weight
Hb (g/l)
PCV %
24
140
40
28
145
45
34
150
47
term
168
53
28-32
175
54
32-36
190
59
36-40
190
59
term
190
59
<1000g
70
1000-1500g
80 (70-114)
1500-2000g
95 (80-114)
birth
3 days
2 months
Consequences
Benefits
Clinical studies have been unable to determine unambiguous benefits of red cell transfusion and precise
criteria for transfusion. The following may assist in clinical decision making:
1. Effect on weight gain:
Minimal effect on weight gain was shown in two controlled trials of transfusion (to keep Hb >
100g/L or transfused at mean Hb 115 g/L) 5, 6
2. Breathing patterns in stable preterm infants:
A controlled study found that benefit from red cell transfusion in 1 3 month old preterm infants
with haematocrit < 30 was predicted by presence of heart rate > 152 bpm, apnea/bradycardia
or lactic acidosis 7 .
A controlled study comparing albumin and red cell transfusion in preterm infants with a mean
Hb < 10g/L found no difference in the reduction of clinically significant apnea between the
two groups 8 .
Uncontrolled studies (before and after) have suggested a reduction in apnea from red cell
transfusion 1 .
3. Heart rates, oxygen consumption and cardiac outputs of stable preterm infants:
A controlled study in stable preterm infants with Hb < 10g/L found no change in heart rate,
cardiac output or central venous oxygen tension difference in infants transfused red cells
compared to infants transfused albumin 8
Several uncontrolled studies have shown reductions in heart rate and cardiac output after
transfusion 1
4. Subclinical tissue acidosis:
An uncontrolled trial of red cell transfusion in ventilated preterm infants < 1500g (mean hct =
33 pre transfusion) demonstrated an increase in regional oxygen delivery and tissue pH in
contrast to colloid infusion, which had no effect 9
A controlled trial showed a reduction in serum lactate in transfused anaemic (HCT < 29)
infants with BPD or apnoea/bradycardia 10
Harms
Potential adverse consequences of neonatal blood transfusion include:
1. Volume overload avoided by awareness of potential, avoidance of rapid transfusion rates in
isovolaemic neonates and use of frusemide where indicated. Partial exchange may be indicated for
infants with heart failure (infants with cardiac disease, hydrops or polycythaemia)
2. Immunosensitisation shown in an RCT to be avoided by use of leucocyte depletion filter 11
3. Graft versus host disease rare complication of neonatal transfusion with usually fatal outcome avoided by irradiation
4. Metabolic derangement
Hyperkalaemia avoid rapid transfusion with old blood in infants at risk (< 27 weeks gestation
and < 72 hours age or with renal impairment)
Hypocalcaemia monitor with large volume transfusions 1 LI>
Hypomagnasaemia monitor with large volume transfusions 1
5. Transmission of infection - The risk of seronegative infective blood donation calculated by the
Victorian Red Cross Blood Bank (data from 1994 to 1995) was 1) HBV 6.45 per million donations; 2)
HCV 4.27 per million donations; and 3) HIV 0.79 per million donations 12
Cytomegalovirus risk reduced to < 1% by use of CMV negative blood and/or leucocyte
depletion filters 13-15 ,
Other viruses - Hepatitis B virus, hepatitis C virus, HIV and HTLV1/2 viruses donors routinely
screened
Diagnosis
Criteria for neonatal blood transfusion
Criteria of blood transfusion are arbitrary. Unequivocal benefits of red cell transfusion have not been
demonstrated in randomised trials 1, 16 .
Consider red cell transfusion for neonates (term or preterm) and infants < 4 months of age if:
Haemoglobin < 120 g/L (hct < 36) and severe pulmonary or heart disease
Acute blood loss > 10% of blood volume and evidence of cardiovascular compromise
Haemoglobin < 80 g/L in a stable newborn infant, or
Haemoglobin < 9-10 g/l, low reticulocyte count (<2%) and symptomatic of anaemia
In infants > 4 weeks of age, testing should include a reticulocyte count. Infants with reticulocyte counts >
2% are unlikely to suffer increasing anaemia.
Pre-transfusion testing and patient identification
Pre-transfusion testing is undertaken to provide suitable blood for a patient which will not cause a
haemolytic transfusion reaction, and which will have an adequate life span after transfusion.
This is achieved by 1. Accurate identification of patient at time of collection of specimen (hand label specimen tubes and
transfusion order).
2. Ascertaining patients ABO + Rh group in order to provide ABO + Rh compatible blood.
3. Having in place an independent Check Group System so that blood is not released for the patient
before group is checked.
4. Screening the materanl sample
5. Crossmatching suitable units and having a second person check the crossmatch paper work before
release of the blood, if possible.
6. Requiring two persons (medical officer or nurse and one other) to ensure the correct unit of blood is
given to the correct patient, and that this is documented in the patients notes.
Treatment
RPAH Blood Bank guideline for Neonates
Blood transfusion:
1. Inform the parents of need for transfusion
2. In stable preterm infants: give packed red cells 20 mls / kg 23 over 4 hours with frusemide 1 mg/kg
IVI at beginning of transfusion
3. For acute blood loss: give whole blood or pack red cells 20 mls / kg or volume of estimated blood
loss titrated to infants response to transfusion (correction of tachycardia)
4. Use CMV negative blood
5. Use irradiated blood
6. Use a leucocyte depletion filter
7. Ensure all blood bank procedures are adhered to
Prevention of need for transfusion
1. Delayed cord clamping controlled trials in premature infants have failed to show an increase in
infants haematocrit or reduction in rate of intraventricular haemorrhage with delayed cord clamping
17-20
2. Minimise iatrogenic losses appropriate microsampling with return of the unused blood used to clear
the line of fluid and use of non-invasive monitoring should reduce red cell transfusion requirements
of premature infants.
3. Autologous transfusions although feasible it is difficult to collect, store and ensure sterility and
identification of autologous blood 1
4. Erythropoietin (rhEPO) it is not possible at present to recommend the routine use of rhEPO in
preterm infants. Evidence from at least 20 RCTs of rhEPO to date have shown: 1, 21
RhEPO and iron results in short term improvements in marrow erythroid cellularity, blood
reticulocyte counts and improvements in haematocrits
RhEPO reduces the numbers of infants receiving blood transfusion and the number of
transfusions received by premature infants.
However, benefits of rhEPO are limited by:
Reduced effect in sick , extremely premature infants who are the recipients of most
transfusions,
Need for early transfusion is not affected by use of rhEPO. Most extremely premature
infants receive early blood transfusion
New practices of reducing donor exposure limit the exposure of preterm infants to
multiple donors
Risk of infection or adverse event resulting from blood transfusion is low
Continued use of rhEPO requires subcutaneous injections
Reducing exposure to multiple donors use of dedicated donor packs
Use of multiple paediatric transfer packs allows infants to be multiply transfused from the same
donor pack and limits infant exposure to multiple donors 21
Use of blood with expiry times < 35 days facilitates use of multiple transfusions from a single donor
the potassium level in the supernatant, although potentially reaching levels of 50-80 mmol/L, only
expose the infant to 0.5 mmol potassium per 20 mls of blood safe if given over hours 1, 22
Directed transfusion
An audit of blood donations to the NSW Red Cross Blood Transfusion Service showed a non-significant
trend to increased rates of hepatitis B and C infection in directed donations compared to the volunteer
homologous donations. Although not feasible acutely for urgent transfusion of sick neonates, if requested
may be obtained for transfusion of stable preterm infants.
If parents express a wish to donate blood for their own child, the procedure is:
1. Order a group and Coombs on the neonate
2. Order group, antibody screen, haemoglobin, haemolysin screen and CMV test on parent for testing
at RPAH
3. Assess the suitability of the parent (see below). If the mother has antibodies and/or the baby has a
positive direct antiglobin test then the situation must be discussed with a Haematologist.
4. An appointment is made by ringing Maureen Ingram, Autologous Clinic, Red Cross 9229 4444. At
this time the parent will have to answer preliminary questions on the telephone to assess suitability.
5. The doctor looking after the baby must complete a directed donation form. You should stipulate if
you require the unit to be made into a packed cell.
6. Inform Blood Bank, RPAH to expect a directed donation for the infant.
7. The parent will be required to fill out the Donor Declaration Form at Red Cross prior to collection.
Routine donor screening is performed at Red Cross at the time of collection, and it can take up to 3
working days for the donor unit to be cleared. Units found to be positive for any infectious markers
are unsuitable.
Notes:
1. If parent is same ABO and Rh group as the infant then he/she would be suitable. If the baby is
group A or B and the parent is group O, Rh compatible, then he/she would need to be haemolysinfree and the units made into packed cells. If the baby is Rh negative and parent Rh positive, then
he/she would be unsuitable.
2. All donations from parents must be irradiated.
3. Blood should be CMV negative, however the Neonatologist looking after the baby may elect to take
responsibility for using CMV positive blood and ensure that it is filtered prior to use in the Nursery,
to reduce the risk of transmission.
4. The haematologists have strong reservations about the use of maternal blood for neonates because
of the possibility of white cell or platelet antibodies in the mother's serum, which are not detected by
routine testing. Ideally any maternal blood should be washed at Red Cross prior to transfusion. This
would limit the collection to only one transfusion with a 24-hr expiry and could not be arranged
quickly or out of normal working hours. The Neonatologist looking after the baby may elect to take
responsibility for using unwashed maternal blood.
5. All paternal donations must be fully cross-matched against infant's serum and against maternal
specimen if applicable.
6. The cost of directed donations is $250 to the patient.
Key Points
Key Points
Level of Evidence
Clinical studies have been unable to determine unambiguous benefits of red
cell transfusion and precise criteria for transfusion
Immunosensitisation shown in an RCT to be avoided by use of leucocyte
depletion filters
11
Cytomegalovirus risk reduced by use of CMV negative blood and/or leucocyte
depletion filters
13-15
Graft versus host disease prevented by irradiation and/or leucocyte depletion
filters
In stable preterm infants: give packed red cells 20 mls / kg over 4 hours
23
Give frusemide 1 mg/kg IVI at beginning of transfusion
For acute blood loss: give whole blood or pack red cells 20 mls/kg, or volume
of estimated blood loss titrated to infants response to transfusion (eg
correction of tachycardia)
Use of multiple paediatric transfer packs allows infants to be multiply
transfused from the same donor pack and limits infant exposure to multiple
donors
22
RhEPO reduces the numbers of infants receiving blood transfusion and the
number of transfusions received by premature infants
1, 21
References
1. Hume H, Bard H. Small volume red blood cell transfusions for neonatal patients. Transfusion Medicine
Reviews 1995; IX, No 3: 187-199.
2. Lundstrom U, Siimes MA, Dallman PR. At what age does iron supplementation become necessary in
low-birth-weight infants? J Pediatr. 1977; 91: 878-83.
3. Oski & Naiman. Haematologic Problems in the Newborn.
4. Chessells. Clinical Paediatric Physiology ed.Godfrey & Baum.
5. Blank JP, Sheagren TG, Vajaria J, Mangurten HH, Benawra RS, Puppala BL. The role of RBC
transfusion in the premature infant. Am J Dis Child. 1984; 138: 831-3.
6. Meyer J, Sive A, Jacobs P. Empiric red cell transfusion in asymptomatic preterm infants. Acta Paediatr.
1993; 82: 30-4.
7. Ross MP, Christensen RD, Rothstein G, Koenig JM, Simmons MA, Noble NA, Kimura RE. A randomized
trial to develop criteria for administering erythrocyte transfusions to anemic preterm infants 1 to 3 months of
age. J Perinatol. 1989; 9: 246-53.
8. Bifano EM, Smith F, Borer J. Relationship between determinants of oxygen delivery and respiratory
abnormalities in preterm infants with anemia. J Pediatr. 1992; 120: 292-6.
9. Moller JC, Schwarz U, Schaible TF, Artlich A, Tegtmeyer,FK; Gortner L. Do cardiac output and serum
lactate levels indicate blood transfusion requirements in anemia of prematurity? Intensive Care Med.
1996y; 22: 472-6.
10. Bard H, Fouron JC, Chessex P, Widness JA. Myocardial, erythropoietic, and metabolic adaptations to
anemia of prematurity in infants with bronchopulmonary dysplasia. J Pediatr. 1998; 132: 630-4.
11. Bedford-Russell AR, Rivers RP, Davey N. The development of anti-HLA antibodies in multiply
transfused preterm infants. Arch Dis Child. 1993; ,b>68: 49-51.
12. Whyte GS, Savoia HF. The risk of transmitting HCV, HBV or HIV by blood transfusion in Victoria. Med
J Aust. 1997; 166: 584-6.
13. Bowden RA; Slichter SJ, Sayers M, Weisdorf D, Cays M, Schoch G, Banaji M, Haake R, Welk K,
Fisher L, et-al. A comparison of filtered leukocyte-reduced and cytomegalovirus (CMV) seronegative blood
products for the prevention of transfusion-associated CMV infection after marrow transplant. Blood. 1995;
86: 3598-603.
14. Bowden RA, Slichter SJ, Sayers MH, Mori M, Cays MJ, Meyers JD. Use of leukocyte-depleted platelets
and cytomegalovirus-seronegative red blood cells for prevention of primary cytomegalovirus infection after
marrow transplant. Blood. 1991; 78: 246-50.
15. Gilbert GL, Hayes K, Hudson IL, James J. Prevention of transfusion-acquired cytomegalovirus infection
in infants by blood filtration to remove leucocytes. Neonatal Cytomegalovirus Infection Study Group.
Lancet. 1989; 1: 1228-31.
16. Ramasethu J, Luban LC. Red blood cell transfusions in the newborn. Semin Neonatol. 1999; 4: 5-16.
17. McDonnell M, Henderson-Smart DJ. Delayed umbilical cord clamping in preterm infants: a feasibility
study. J Paediatr Child Health. 1997; 33: 308-10.
18. Grajeda R, Perez-Escamilla R, Dewey KG. Delayed clamping of the umbilical cord improves
hematologic status of Guatemalan infants at 2 mo of age. Am J Clin Nutr. 1997; 65: 425-31.
19. Hofmeyr GJ, Gobetz L, Bex PJ, Van der Griendt M, Nikodem C, Skapinker R, Delahunt T.
Periventricular/intraventricular hemorrhage following early and delayed umbilical cord clamping. A
randomized controlled trial. Online J Curr Clin Trials. 1993 Doc No 110.
20. Kinmond S, Aitchison TC, Holland BM, Jones JG, Turner TL, Wardrop CA. Umbilical cord clamping and
preterm infants: a randomised trial. BMJ. 1993; 306(6871): 172-5.
21. Widness JA, Strauss RG. Recombinant erythropoietin in treatment of the premature newborn. Semin
Neonatol. 1998; 3: 163-171.
22. Strauss RG, Burmeister LF, Johnson K, James T, Miller J, Cordle DG, Bell EF, Ludwig GA. AS-1 red
cells for neonatal transfusions: a randomized trial assessing donor exposure and safety. Transfusion. 1996;
36: 873-8.
23. Paul DA, Leef KH, Locke R, Sterfano JL. Transfusion volume in very low birth weight infants: a
randomized study of 10 vs 20 cc/kg. Pediatrics. 104: S3: 739.
Last Reviewed: June, 2000