Blood transfusion in neonate

1. Restrictive (Low) Transfusion Threshold
Compared With
Liberal (High) Transfusion Threshold

2. Dr Abubakr Hassan Tammam
Neonatologist
Under Supervision Of
Dr Hassam
Neonatology Consultant

3.  Anemia occur frequently in neonates admitted to NICUs,
particularly in PT neonates.
 In addition, the RBCs circulating in preterm infants have a
reduced life span compared with those in full term infants,
which contributes to the anemia of prematurity.
 More than 80% of these PT are transfused with RBCs during
their initial hospitalization.
Updates in Red Blood Cell and Platelet Transfusions in Preterm Neonates Am J Perinatal 2019;36(suppl S2):S37–S40.

4. Anemia in neonates can be physiological, but can also be
caused by non-physiological factors such perinatal or
peripartum complications, clinical conditions such as sepsis
and cardiorespiratory disease, and hemolytic disease of the
fetus and newborn.
In PT, the physiological anemia is exacerbated by early
clamping of the umbilical cord, blood loss from phlebotomy
for laboratory monitoring and delayed erythropoiesis,

5. one of the most important causes of anemia in PT is
iatrogenic blood loss due to frequent laboratory testing.
Estimates of iatrogenic blood loss due to laboratory testing in
the first month of life in preterm neonates admitted to a
NICU may amount up to one-third of the total blood volume

6.  Symptomatic anemia occurs when the RBC mass is not
adequate to meet the oxygen demands of tissues.
 Signs that may reflect symptomatic anemia include increased
resting heart rate, acidosis, poor growth, decreased energy to
nipple feed, apnea, and need for increased respiratory
support.

7.  The main treatment modality for neonatal anemia is still
based on the administration of RBC transfusions, but there
is no international consensus regarding optimal hemoglobin
thresholds for RBC transfusions in PT.
 The optimal Hb value for growth and uncomplicated
development for infants and neonates is unknown.
Lopriore E. Updates in red blood cell and platelet transfusions in preterm neonates. Am J Perinatol. 2019;36(S 02):S37-S40

8.  Transfusions are a temporary measure and have the
disadvantages inhibiting erythropoiesis and being associated
with risks of infection .
 GVHD
 TRALI
 TACO
 TRAGI and NEC,
 toxic effects of anticoagulants or preservatives.
 increased risk of death
 IVH,
 ROP.
 transient increase in respiratory support.
Geneva, 2014. Accessed May 7, 2019

9. When To Transfuse .

10.  It remains uncertain what target HCT or hemoglobin will optimally
balance the risk and benefits of this intervention.
 Various factors influence the threshold, including acuity of blood
loss, gestational age (GA), severity of illness, need for respiratory
support, or if the infant will undergo major surgery within 72
hours

11. Indication of transfusion
1. Acute blood loss that is greater than 20 percent of blood
volume.
2. Acute blood loss that is greater than 10 percent of blood
volume with symptoms of decreased oxygen delivery (such
as persistent acidosis) after volume resuscitation.
3. Ongoing hemorrhage

12. Restrictive Blood Transfusion Approach For Neonate.
 For infants requiring moderate or significant mechanical
ventilation, defined as mean air pressure (MAP) >8 cm H2O
and FiO2 >0.4 on a conventional ventilator, or MAP >14 and
FiO2 >0.4 on high frequency ventilator, and with a
hematocrit ≤30% (hemoglobin ≤10g/dL).
 For infants requiring minimal mechanical ventilation,
defined as MAP ≤8 cm H2O and/or FiO2 ≤0.4 on a
conventional ventilator, or MAP <14 and/or FiO2 <0.4 on
high frequency, and with a hematocrit ≤25% (hemoglobin
≤8 g/dL).

13.  For infants on supplemental oxygen who are not requiring
mechanical ventilation, transfusions can be considered if the
hematocrit is ≤20% (hemoglobin ≤7 g/dL) and one or more of
the following conditions is present:
• ≥24 hours of tachycardia (heart rate >180 beats per minute) or
tachypnea (RR >60breaths per minute)
• Doubling of the oxygen requirement from the previous 48 hours
• Serum lactate ≥2.5 mEq/L or an acute metabolic acidosis (pH <7.2)
• Weight gain <10 g/kg/day over the previous four days while receiving
≥120 kcal/kg/day
• if the infant will undergo major surgery within 72 hours kcal/kg/day

14. Target Hemoglobin Or Hematocrit

15. Results of clinical trials in ELBW , have reported that a restrictive
(low) transfusion threshold compared with a liberal (high)
threshold does not increase mortality or serious morbidity, and
reduces exposures to transfusion. So using a restrictive approach
for neonatal transfusions that is based upon HCT triggers and the
respiratory support/illness severity of the infant, supported by data
from a met analysis from 2011 and 2012 and the subsequent
following largest to date clinical trials:

16. (PINT) study
 The Premature Infants in Need of Transfusion (PINT) study: a
randomized, controlled trial of a restrictive (low) versus liberal
(high) transfusion threshold for extremely low birth weight
infants. J Pediatric. 2006;149(3):301-307.
 found no significant difference in death or brain injury by
ultrasound in a ‘restrictive’ transfusion group (Hb 7.5– 11.5
g/dl) compared to a higher transfusion threshold group (Hb
8.5–13.5 g/dl).

17. A Cochrane meta-analysis published in 2011 included five studies
comparing low versus high Hb concentration thresholds for RBC
transfusion in VLBW newborns and reported no significant
difference in mortality and morbidities related to prematurity
Low versus high hemoglobin concentration threshold for blood transfusion for preventing morbidity
and mortality in very low birth weight infants. Cochrane Database Syst Rev. 2011; 11:CD000512

18.  In a large RCT on 1013 ELBW (ETTNO study), the primary
outcome of death or neurodevelopmental impairment (CP,
cognitive deficit or severe visual or hearing impairment) at 24
months corrected age (CA) was similar between the restrictive
versus liberal threshold groups
 The risk of secondary outcomes was also similar between the
restrictive and liberal threshold groups including death alone
cognitive deficit at 24 months corrected age also NEC requiring
surgery BPD treatment for ROP and growth.
Effects of Liberal vs Restrictive Transfusion Thresholds on Survival and Neurocognitive Outcomes in
Extremely Low-Birth-Weight Infants: The ETTNO Randomized Clinical Trial. JAMA 2020; 324:560.

19. In another large, RCT include 1824 ELBW infants performed by
the NICHD Neonatal Research Network (TOP trial),
 the primary outcome of death or neurodevelopmental
impairment (moderate or severe CP, severe vision or hearing
loss, cognitive delay was similar between the low and high
target threshold groups
 At two years of age, death rates were similar for low and high
target groups as were the rates for neurodevelopmental
impairment and serious adverse events
Higher or Lower Hemoglobin Transfusion Thresholds for Preterm Infants. N Engl J Med 2020; 383:2639.

21. In addition, another analysis of 628 PT enrolled in the PENUT trial
reported an increase in each red cell transfusion was associated
with a decrease in cognitive transfusion, motor points per
transfusion, and language Development
Transfusions and neurodevelopmental outcomes in extremely low gestation neonates enrolled in the PENUT Trial: a
randomized clinical trial. Pediatr Res 2021; 90:109.

22. Erythropoietin
Systematic reviews from 2017 and 2019 that reported early and late
administration of EPO reduced the number of RBC transfusions
Infants who receive appropriate and timely doses of EPO or
darbepoetin (a long-acting EPO) therapy require fewer transfusions
and are exposed to fewer donors.
Effect of High-Dose Erythropoietin on BloodTransfusions in Extremely Low Gestational Age Neonates:
Post Hoc Analysis of aRandomized Clinical Trial. JAMA Pediatr 2020; 174:933.

23. Administration
In the neonate, transfusions generally are given as packed red blood
cells (PRBCs) in aliquots of 10 to 20 mL/kg, over two to four hours.
In some circumstances, such as hemodynamic instability or
hypovolemia due to blood loss, a smaller volume (10mL/kg) is given
more rapidly (over one to two hours). In extremely low birth
weight(ELBW) infants (BW <1000 g)
Red blood cell transfusions in the newborn Literature review current through: Sep 2022Uptodat 2022

24. Summary And Recommendations

25.  Evidence based on clinical trials has shown that a
restrictive transfusion strategy (low Hb/Hct threshold)
versus a liberal approach (high Hb/Hct threshold) results
in fewer transfusions and does not increase the risk of
death or serious morbidity.
 A restrictive approach for neonatal transfusions that is
based upon HCT triggers and the respiratory support
required by the infant recommend

26. The advantage to using lower hemoglobin thresholds to guide
transfusion practice is a reduction in the number of transfusions
given to infants.
Bell EF. Arch Dis Child Fetal Neonatal Ed 2022

27. Also, prevention of neonatal anemia
1. Delayed cord clamping at birth, for at lest 30 -60 sec.
2. measures to minimize phlebotomy blood losses and samples
3. and good nutritional practices are also important means of
limiting the need for blood transfusion.
Seidler AL, Gyte GML, Rabe H, et al. Umbilical cord management for newborns <34 weeks’ gestation: a meta-
nalysis. Pediatrics 2021;147:e20200576.

28. To optimize transfusion guidelines,.
 Further investigations and large well designed trials in preterm
neonates are urgently needed.
 Until then, blood product transfusions in neonates should be
used with caution and neonatologists should be aware that the
evidence concerning the risks and benefits of transfusions in
neonates is fairly limited.