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Pediatrics and Neonatology (2017) xx, 1e4

Available online at www.sciencedirect.com

ScienceDirect

journal homepage: http://www.pediatr-neonatol.com

Review Article

Red blood cell transfusion in infants and

children e Current perspectives
Natasha Ali

Section of Haematology, Department of Pathology & Laboratory Medicine/Oncology, Aga Khan

University, Pakistan

Received Oct 4, 2016; received in revised form Feb 11, 2017; accepted Oct 3, 2017
Available online - - -

Key Words Children routinely receive packed red blood transfusion when they are admitted in the inten-
infants and children; sive care unit or undergoing cardiac surgeries. These guidelines aim to summarize literature
red blood cells; and provide transfusion triggers exclusively in infants and children.
transfusion trigger Copyright ª 2017, Taiwan Pediatric Association. Published by Elsevier Taiwan LLC. This is an
open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/
by-nc-nd/4.0/).

1. Introduction 3. Physiologic response to anemia

In older children and adults, transfusion is not performed
very often. The most commonly transfused groups are
children in pediatric intensive care units or those under-
going cardiac surgery. Many caregivers have postulated
about the life-saving properties of RBC transfusion in a
defined patient population. However, recent studies have
demonstrated potential deleterious effects of liberal use of
blood in critically ill adults and children.1
2. Literature search
An electronic search of MEDLINE was performed. The search
terms used included “red blood cells” and “transfusion” in
combination with “transfusion trigger”, “critical illness”
“sepsis” and “children”.
E-mail address: natasha.ali@aku.edu.
The primary objective of RBC transfusion is to increase
oxygen delivery to tissues to preserve organ function in
compromised situations. Oxygen delivery is dependent
mainly on 1) haemoglobin, 2) cardiac output and 3)
percent saturation (SaO2). When fully saturated each
gram of haemoglobin (Hb) can carry 1.34 ml of oxygen at
normal body temperature. The data suggest that simply
increasing the oxygen delivery by RBC transfusion does
not lead to increased oxygen utilization. The mechanisms
implicated include changes in 2, 3 diphosphoglycerate,
adenosine triphosphate and quantity of free haemoglo-
bin. These factors contribute to the reduction of local
oxygen delivery after transfusion and may be responsible
for negative outcomes of RBC transfusion in critically
ill patients despite an increase in global haemo-
globin concentration and theoretical increase in oxygen
delivery.2e4

https://doi.org/10.1016/j.pedneo.2017.10.002
1875-9572/Copyright ª 2017, Taiwan Pediatric Association. Published by Elsevier Taiwan LLC. This is an open access article under the CC BY-
NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).

Please cite this article in press as: Ali N, Red blood cell transfusion in infants and children e Current perspectives, Pediatrics and
Neonatology (2017), https://doi.org/10.1016/j.pedneo.2017.10.002
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2 N. Ali
4. Anemia and RBC transfusion in intensive
care units
Severe sepsis and septic shock are major healthcare prob-
lems in adults and children.5 The pathophysiology of sepsis
is such that it involves decreased oxygen delivery and
myocardial dysfunction. The physician’s goal for these pa-
tients is to ensure adequate oxygen delivery by augmenting
their cardiac output and hemoglobin level.6 Two surveys
addressed the issue of pediatric intensivists preferring to
maintain a high hemoglobin level in children with sepsis.7,8
Rivers et al.6 reported an improved outcome in adults with
severe sepsis when the central venous oxygen saturation
was maintained at >70% in the first 6 h after presentation;
the proposed treatment strategy for this was RBC trans-
fusion to reach a central venous oxygen saturation of 70% or
more.
2008 guidelines of the survival sepsis campaign recom-
mended that adults admitted with sepsis should undergo
transfusion in the first 6 h to maintain a target hematocrit
of >30%. Once the hypoperfusion of tissues is resolved, the
hemoglobin can be maintained between 7.0 gm/dl and
9.0 gm/dl. The cutoff for RBC transfusion is recommended
at a level below 7.0 gm/dl.9 Lacroix et al.10 reported their
randomized control trial in which a transfusion trigger of
7.0 gm/dl was compared with 9.5 gm/dl in stabilized crit-
ically ill children. It was seen that a lower threshold of
7.0 gm/dl was safe in this patient population.
With improvements in the practice of medicine, in order
to provide continuous quality of care repeated phlebotomy
is performed due to perpetual demand of laboratory in-
vestigations. This results in iatrogenic anemia. In the
neonatal ICU setting, this problem has been extensively
studied. Special protocols can be introduced to reduce
blood sampling in the ICU.11 Point of care testing (POCT) is
one methodology that has helped in this setting. In com-
parison to traditional phlebotomy, POCT requires a small
volume of blood resulting in decreased blood loss subse-
quently leading to fewer transfusions.12
5. Haemoglobin level trigger for transfusion
Weiskopf et al.13 studied healthy volunteers undergoing
isovolemic hemodilution and found no evidence of impaired
tissue oxygenation until the haemoglobin concentration
decreased to 4 5 gm/dl. These findings have not been
extensively validated and are dependent on the underlying
clinical condition. However, children seem at least as
capable as adults in their ability to compensate for lower
Hb concentration with increased oxygen extraction and
cardiac output.14
Lackritz et al.15 retrospectively analyzed over 2400 pe-
diatric admissions in a Kenyan hospital that showed 29% of
all children admitted had a Hb of <5 gm/dl. Majority of
these patients had malaria. In all these cases, severe ane-
mia was associated with a significantly increased mortality.
Another prospective study was conducted in 287 children,
also with malaria. These children were randomized to
either blood transfusion or iron replacement for 28 days
(total 114 children). In 173 children, respiratory distress or
a hematocrit of <12% was present. Therefore they were
Please cite this article in press as: Ali N, Red blood cell transfusion in infants and children e Current perspectives, Pediatrics and
Neonatology (2017), https://doi.org/10.1016/j.pedneo.2017.10.002
transfused at presentation. Twenty-four deaths were re-
ported in the study. Twenty-three of those children had an
admission hematocrit of <12%. Of the children randomized
to receive iron therapy, one child died and ten subse-
quently required RBC transfusion.16 These children may
represent pediatric patients in developing countries and
accentuate the imminent risk of low Hb level and the
physiologic mechanisms to maintain delivery of oxygen in
the setting of severe anemia.
6. Transfusion in neonates
In 15%e50% of critically ill pediatric patients admitted in
the ICU, RBC transfusion is carried out at some point during
their stay.17 More frequently, packed red blood cell trans-
fusion is a common practice in preterm infants admitted to
neonatal intensive care units. Neonates weighing less than
1500 g are the ones with increased transfusion needs. About
40% of neonates weighing 1000e1500 g at birth and 90% of
those weighing <1000 g may receive a mean of five RBC
transfusions during their hospital stay.18 A recent interna-
tional survey of transfusion practices for extremely pre-
mature infants showed that the degree of oxygen
requirement (44.7% of respondents) and need for respira-
tory support (44.1% of respondents) were considered the
most important triggers for transfusion.19 Kasat et al.20
recently observed that tachycardia was the most sensitive
predictor of improvement resulting from RBC transfusion.
This study also observed no significant changes after
transfusion in critically ill, ventilator-dependent neonates,
probably due to the complex physiology of neonatal respi-
ratory system. In contrast, the results of this study showed
an increased oxygen requirement after transfusion in a
cohort of critically ill premature neonates in the first week
of life which was likely caused by volume overload. For
these reasons, the conclusion of the study was judicious
RBC transfusion for critically ill neonates.
Bateman and colleagues21 published the results of a
multicenter, prospective, observational study that explored
the frequency of anemia, phlebotomy and RBC transfusions
in critically ill children admitted in PICUs. Anemia was
present in nearly three - fourths of these children. Almost
half of these children received at least one RBC transfusion
during their stay. Only 4% of children received transfusion
after one week of hospitalization. Blood loss from frequent
phlebotomy was a significant and independent risk factor
for RBC transfusion (Key recommendations are summarized
in Table 1).
7. Conclusion
The College of American Pathologists suggests considering
the patient’s clinical status and the amount of blood loss
when making the decision to transfuse.22 The lowest rec-
ommended threshold is a level of haemoglobin less than
6 gm/dl. These recommendations emphasize the impor-
tance of considering tissue oxygenation by monitoring the
heart rate, arterial blood pressure, lactate levels and
mixed venous oxygenation rather than using any one single
Hb value in clinical decision - making. The American Society
of Anesthesiologists and the Canadian blood transfusion
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Red blood cell transfusion 3

Table 1 Key recommendations for practice.

Clinical recommendation Evidence Comments
rating
The threshold for transfusion of red blood cells should A RCTsa in children with a critical illness1,10
be a hemoglobin level of 7 gms/dl
Maintenance hemoglobin should be between 7 gms/dl e 9 gms/dl A Cochrane review26
A restrictive transfusion strategy (hemoglobin of B RCTs in children with a critical illness10
7 gms/dl e 9 gms/dl) should not be used in preterm infants
or children with cyanotic heart disease, severe hypoxemia,
active blood loss or hemodynamic instability
a
RCT: Randomized Control trial.

guidelines both recommend against the use of a single
transfusion trigger.23,24 Unfortunately, most published
guidelines for RBC transfusion in critically ill children are
either based on expert opinion or derived from studies
performed in critically ill adults.25
Studies have established that almost all patients
admitted in the ICU receive at least one RBC transfusion per
stay. The most common reason is iatrogenic blood loss
through multiple blood sampling for investigations.

Multiple choice questions Conflict of interest

1. The most sensitive predictor of packed red cell trans- There is no conflict of interest.
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