American Journal of Therapeutics 9, 396–405 (2002)

Perioperative Blood Transfusion Therapy in

Pediatric Patients

Heather A. Hume1* and Pierre Limoges2

In general, transfusion guidelines for non-neonatal pediatric patients are similar to those for adults.
However, some differences do exist and certain precautions may be necessary particularly in the
setting of massive transfusions. We review these differences as they apply to general pediatric
surgery outside of the neonatal period, with respect to the transfusion of red blood cells (RBCs),
platelets, fresh-frozen plasma (FFP), and cryoprecipitate. We include a discussion of the indications
for transfusion and practical considerations such as dosing and administration. Finally, we briefly
review the use of directed donations and specialized (irradiated, CMV seronegative) blood com-
ponents.

Keywords: perioperative blood transfusion, pediatric blood transfusion.

INTRODUCTION RED BLOOD CELL TRANSFUSIONS

In general, transfusion guidelines for nonneonatal pe-
diatric patients are similar to those for adults. Some
differences do exist, however, and certain precautions
may be necessary, particularly in the setting of mas-
sive transfusions. We review these differences as they
apply to general pediatric surgery outside the neona-
tal period with respect to the transfusion of red blood
cells (RBCs), platelets, fresh-frozen plasma (FFP), and
cryoprecipitate. For guidelines concerning transfusion
therapy in the neonatal period or transfusions in par-
ticular surgical settings (eg, pediatric cardiovascular
surgery), the reader is referred to several recent re-
views on these topics.1–4 Perioperative autologous
blood donation and transfusion in children have also
been reviewed in depth recently5 and are not ad-
dressed in this review.
1
Executive Medical Director, Canadian Blood Services, Ottawa,
Ontario, Canada; 2Ste. Justine Hospital, Montréal, Québec, Canada.
*Address correspondence to: Dr. Heather Hume, Executive Medi-
cal Director, Canadian Blood Services, 1800 Alta Vista Drive,
Ottawa, Ontario, K1G 4J5 Canada. E-mail: heather.hume@
bloodservices.ca
1075–2765 © 2002 Lippincott Williams & Wilkins, Inc.
Preoperative evaluation
The decision to perform a preoperative hemoglobin
(Hb)/hematocrit (Hct) evaluation depends on the
presence of risk factors for hematologic disease
and/or the risk of perioperative blood loss.
Iron deficiency anemia is the most common hema-
tologic disease of infancy and childhood, primarily as
a result of preterm birth or inadequate iron intake.
Adolescents, particularly girls, are also susceptible to
iron deficiency anemia because of high requirements
due to the growth spurt, dietary deficiencies, and
menstrual blood loss. In the United States, approxi-
mately 9% of 1- to 2-year-olds and 9% of adolescent
girls are iron-deficient; iron deficiency anemia is pres-
ent in 3% of toddlers and 2% of adolescent girls.6
With the increasing ethnic diversity of the North
American population, it is also important to consider
the possibility of the presence of a congenital hemato-
logic disorder, particularly thalassemia or a sickling
hemoglobinopathy. Thalassemia minor results in a
mild microcytic anemia with no clinical consequences;
however, Hb levels in thalassemia intermedia, which
is particularly prevalent in children of Southeast Asian
origin, may be 80 g/L or lower.
Children (and adults) with sickling hemoglobinopa-
thies or sickle cell disease (SCD) are at increased risk
for perioperative complications and therefore require
DOI: 10.1097/01.MJT.0000017424.97313.8C
PERIOPERATIVE BLOOD TRANSFUSION THERAPY IN PEDIATRIC PATIENTS 397

specialized perioperative care, frequently including slightly lower Hb values in children versus adults is
preoperative transfusion therapy.7–10 SCD patients thought to be a result of the increased intraerythro-
must be identified before any surgical intervention cytic concentration of 2,3-diphosphoglycerate, which,
and, except in extreme emergencies, should undergo in turn, results in increased offloading of oxygen to
surgical interventions only in centers experienced in tissues at any given blood oxygen tension.12
the care of such patients. Sickling hemoglobinopathies
Indications for red blood cell transfusion
include sickle cell anemia (homozygosity for Hemo-
globin S [HbS]) and the compound heterozygous dis- There are only two valid reasons for transfusing RBCs
orders Hemoglobin SC (HbSC) disease and HbS/␤ to children: the most common is to correct an (or avoid
thalassemia. Persons with sickle cell trait (ie, hetero- an imminent) inadequate oxygen-carrying capacity
zygotes for Hemoglobin A and HbS) are not at in- that is caused by an inadequate RBC mass; the second
creased risk for perioperative complications. SCD is and rarer indication is to suppress endogenous Hb/RBC
found predominantly (but not exclusively) in black production in selected thalassemia or SCD patients.
persons (persons of African origin). In addition to this Indices of oxygen delivery and tissue oxygenation
group, SCD also occurs in persons of Mediterranean, may accurately indicate the need to transfuse RBCs;
Indian, Middle Eastern, and South and Central Ameri- however, invasive monitoring is required to generate
can origins. these indices. Decisions about RBC transfusions are
A complete blood cell count (CBC) alone is not an usually made on the basis of easily available but less
appropriate test to screen for the presence of SCD, precise clinical data. Although Hb concentration is
because the Hb concentration may be normal in HbSC certainly one important factor to consider in the deci-
disease. In patients over 6 months of age, a CBC and sion to administer an RBC transfusion, most experts
screening test for SCD (eg, a sickling test or a solubility agree that it is not the only factor; in certain situations
test) may be used for preoperative evaluation; in in- such as acute hemorrhage without volume replace-
fants 6 months of age or less, a screening test may not ment, it may even be misleading. As discussed in de-
detect the presence of HbS (because of the relatively tail in several reviews, healthy adults and children
high levels of Hemoglobin F and low levels of HbS), have an impressive capacity to increase oxygen deliv-
and a more definitive test such as hemoglobin electro- ery to tissues.13–16 A recent study (albeit in a small
phoresis should be performed. number of patients/volunteers) demonstrated that
At our institution, preoperative CBCs are per- healthy adults subjected to acute normovolemic he-
formed routinely in infants less than 12 months of age, modilution were able to tolerate an Hb concentration
and tests to detect SCD are performed in populations of 50 g/L with no adverse effects.17 It seems reason-
at risk as described previously. Otherwise, CBCs are able to assume that this would also be the case for
performed only if the clinical evaluation is suggestive otherwise healthy adolescents and older children.
of the presence of anemia or as a baseline for inter- In 1997, the Canadian Medial Association (CMA)
ventions for which large blood losses are anticipated. published guidelines for RBC and plasma transfusion
In interpreting the CBC in a child, one must remem- for adults and children.18 As background for the de-
ber that the normal values for Hb and mean corpus- velopment of those guidelines, systematic reviews to
cular volume are different from those in adults and identify evidence-based reports on allogeneic RBC
that there are age-related changes (Table 1).11 The and plasma transfusions in adults as well as children
were performed.15,19,20
Table 1. Normal values for hemoglobin concentration Unfortunately, there are few studies in either pedi-
and MCV in infancy and childhood. Adapted from atric or adult settings in which the validity of clinical
Nathan and Orkin.11 criteria has been examined. Thus, the efficacy of RBC
transfusion in most scenarios has not been established
Hemoglobin
(g/L) Hematocrit MCV (fl)
by evidence-based data. At the time that the CMA
guidelines were developed, only seven studies (3 ran-
Age Mean −2 SD Mean −2 D Mean −2 D domized controlled trials and 4 nonrandomized stud-
ies) addressing the indications for RBC transfusions in
1–3 days 185 145 0.56 0.45 108 95 children (excluding neonates or infants less than 4
3–6 months 115 95 0.35 0.29 91 74 months of age or patients with thalassemia or sickle
0.5–2 years 120 105 0.36 0.33 78 70
cell disease) were identified.21–27 Since that time, to
2–6 years 125 115 0.37 0.34 81 75
6–12 years 135 115 0.40 0.35 86 77
these authors’ knowledge, no additional studies ad-
dressing the efficacy of RBC transfusions in pediatric
MCV, mean corpuscular volume. patients have been reported.
American Journal of Therapeutics (2002) 9(5)
398
Of the seven studies referred to, two were per-
formed in children undergoing treatment of acute leu-
kemia in the 1970s and are of historical interest only,
two addressed the treatment of anemia caused by ma-
laria in African children, two addressed the utility of
RBC transfusions to improve tissue oxygenation in
children with sepsis (each arrived at a different and
opposing conclusion), and the remaining study exam-
ined the relation between oxygen delivery and con-
sumption and RBC transfusion after cardiac bypass
surgery.21–27 The results of the studies performed in
Africa are not generalizable to the North American
setting, but they do speak to the tolerance of children
for severe anemia. In one of the studies, there was no
difference in mortality between the transfused and
nontransfused groups in spite of mean admission Hcts
of 0.140 and 0.144, respectively.23 In the second study,
the authors’ conclusion was that in their setting, RBC
transfusions should be administered to children with
congestive heart failure or respiratory distress if the
Hb concentration is less than 50 g/L but in the absence
of cardiorespiratory symptoms or signs only if the Hb
concentration is less than 30 g/L.24
Since the publication of these guidelines, a random-
ized controlled trial of a restrictive versus liberal RBC
transfusion study in critically ill adult patients has
been reported.28 End points measured in this study
were death and the severity of organ dysfunction.
Overall, the 30-day mortality rates were similar in the
two groups; however, the rates were significantly
lower with the restrictive transfusion strategy among
patients who were less acutely ill. The authors con-
cluded that a restrictive RBC transfusion strategy is at
least as effective as a liberal transfusion strategy, with
the possible exception of patients with acute myocar-
dial infarction and unstable angina. Although no such
data are available for children, a similar multicenter,
prospective, randomized study is currently underway
in children admitted to critical care units (J. Lacroix,
personal communication, 2001). This study, when
completed, will represent the only large, prospective,
randomized, controlled trial of RBC transfusion
therapy in children outside the neonatal period (with
the exception of studies performed in children with
SCD or thalassemia).
In the absence of studies that could be used to allow
the practice of evidence-based RBC transfusion
therapy, guidelines for RBC transfusions in children
(as well as adults) have been based on expert opinion.
The recommendations of a National Institutes of
Health-sponsored consensus conference on perioper-
ative RBC transfusion29 published in 1988 stated
the following:
American Journal of Therapeutics (2002) 9(5)
HUME AND LIMOGES
• Available evidence does not support the use of a
single criterion for transfusion such as Hb concen-
tration of less than 100 g/L. No single measure can
replace good clinical judgment as the basis for de-
cision-making regarding perioperative transfusion.
• There is no evidence that mild-to-moderate ane-
mia contributes to perioperative mortality.
The CMA guidelines published in 1997 similarly
stated that “there is no single value of Hb concentra-
tion that justifies or requires transfusion; an evalua-
tion of the patient’s clinical situation should also be a
factor in the decision.”18
In 1996, the American Society of Anesthesiologists
(ASA) Task Force on Blood Component Therapy pub-
lished transfusion practice guidelines.30 Although a
number of years have passed since these guidelines
were developed, in the authors’ opinion, these guide-
lines remain valid (ie, there are no subsequently pub-
lished studies that would invalidate the guidelines).
The members of the task force specifically state that
the guidelines were not intended to apply to children.
Nevertheless, it is our belief that these guidelines can
be used for pediatric patients, with the possible excep-
tion of infants and toddlers. In summary, the recom-
mendations of the task force with respect to RBC
transfusions are as follows:
• Transfusion is rarely indicated when the Hb con-
centration is greater than 100 g/L and is almost
always indicated when it is less than 60 g/L, es-
pecially when the anemia is acute.
• The determination of whether intermediate Hb
concentrations (60–100 g/L) justify or require
RBC transfusion should be based on the patient’s
risk for complications of inadequate oxygenation.
• The use of a single Hb “trigger” for all patients
and other approaches that fail to consider all im-
portant physiologic and surgical factors affecting
oxygenation are not recommended.
• When appropriate, preoperative autologous
blood donation, intraoperative and postoperative
blood recovery, acute normovolemic hemodilu-
tion, and measures to decrease blood loss (delib-
erate hypotension and pharmacologic agents)
may be beneficial.
• The indications for transfusion of autologous
RBCs may be more liberal than for allogeneic
RBCs because of the lower (but still significant)
risks associated with the former.
The last recommendation of the ASA task force
cited here is in fact rather controversial. Although this
group of experts is not alone in recommending more
liberal indications for autologous RBC transfusions
PERIOPERATIVE BLOOD TRANSFUSION THERAPY IN PEDIATRIC PATIENTS
than for allogeneic RBC transfusions, not all experts
agree. In particular, the 1997 CMA guidelines state
explicitly that “indications for the transfusion of au-
tologous blood should be the same as those for allo-
geneic blood.”19
To apply these ASA guidelines to the intraoperative
setting, it is useful, before or during surgery, to esti-
mate the maximal allowable blood loss (MABL). The
MABL can be calculated as follows:
EBV 共Ho − HL兲
MABL =
H0
where EBV is the estimated total blood volume, H0 is
the initial Hct, and HL is the lowest acceptable Hct
(where Hct is expressed as a percentage).31 RBC re-
placement should start earlier if hemodynamic insta-
bility occurs despite adequate volume replacement
and/or if timely laboratory monitoring is lacking.
With respect to the correction of postoperative ane-
mia, the need for iron replacement is often over-
looked. Any child who has had blood loss of more
than 5% of his/her total blood volume should receive
iron replacement after surgery. Unless the losses have
been large, elemental iron at a rate of 3 mg/kg per day
for a period of 2 to 3 months should be sufficient.
Practical considerations
The principles for the choice of blood group of RBC
units for transfusion are the same in children as in
adults, with the exception that in the case of massive
emergency transfusion in a child, one should avoid
the transfusion of Rhesus D antigen (RhD)-positive
blood to an RhD-negative patient. This is especially
important for girls, in whom the development of an
RhD antibody could, in subsequent pregnancies, lead
to hemolytic disease of the newborn.
The quantity of RBCs to be transfused depends on
the Hct of the RBC unit, and that, in turn, depends on
the storage medium. RBCs stored in citrate-
phosphate-dextrose-adenine-1 have an Hct of 0.70 to
0.75; in the absence of ongoing blood losses, a trans-
fusion of 10 mL/kg can be expected to raise the Hb
concentration by approximately 25 g/L. Currently,
most RBCs are stored in additive solutions (eg, AS-1 or
AS-3) and have an Hct of 0.50 to 0.60. To obtain an
increase of 25 g/L, 14 mL/kg must be administered.
When blood centers began using additive solutions
in the late 1980s, concerns were raised about their
safety for use in neonatal and pediatric patients. Cal-
culations of the quantities of the constituents of addi-
tive solutions that would be transfused to neonates
suggested that small volumes (<20 mL/kg) could be
infused without problems but that massive transfu-
399
sions could potentially be harmful.32 At our institu-
tion, we remove the supernatant fluid from RBC units
stored in additive solution for massive (but not small-
volume) transfusion in infants less than 4 months of
age. For infants more than 4 months of age, we do not
routinely remove the supernatant fluid even for mas-
sive transfusion.
Concern has also been raised in the literature about
the risk of hyperkalemia in massive transfusion in pe-
diatric patients. The RBC membrane storage lesion re-
sults in gradual leakage of potassium from the RBCs
to the plasma/preservative medium. At the end of the
permitted storage period (35 days for RBCs stored in
CPDA-1 and 42 days for additive solutions), the su-
pernatant potassium concentrations are approxi-
mately 75 to 100 mmol/L (75–100 mEq/L) and 50
mmol/L (50 mEq/L), respectively. Considering the
volumes of supernatant in each unit, these concentra-
tions correspond to an absolute quantity of potassium
at outdate of 5 to 7 mmol (approximately the same
in the two types of units). The concentration of potas-
sium in the supernatant fluid increases consider-
ably more rapidly in units irradiated before storage
(see below).
In adults, transfusion rates not exceeding 100 to 150
mL/min are rarely associated with significant potas-
sium abnormalities. In pediatric patients, however,
rapid massive transfusion of stored blood has been
reported to lead to hyperkalemia and, in at least one
report, to the death of a neonate.33–36 Situations in
which significant hyperkalemia may occur seem to in-
clude a combination of risk factors, namely, rapid
large-volume transfusion of RBCs near the end of the
permitted storage period, particularly if infused to a
central venous catheter and/or in the presence of low
cardiac output or renal failure. In such high-risk situ-
ations, electrocardiographic monitoring and monitor-
ing of potassium levels should be performed, and, if
possible, especially in young children, RBCs stored for
less than 2 to 3 weeks should be used. In infants less
than 4 months of age, we do not use blood stored for
more than 10 to 14 days for large-volume transfusions
unless the supernatant fluid is removed.
PLATELET TRANSFUSIONS
Indications
The indications for platelet transfusions in patients
with malignancies, particularly acute leukemia, have
been reasonably well studied, and at least some of the
studies have included pediatric patients. Clinical prac-
tice guidelines for platelet transfusion in patients with
cancer have recently been published by the American
American Journal of Therapeutics (2002) 9(5)
400
Society of Clinical Oncology37 and are essentially the
same for children as for adults. With respect to sur-
gery or invasive procedures, these guidelines state
the following:
• In the absence of associated coagulation abnor-
malities, a platelet count of 40 to 50 × 109/L is
sufficient to perform major invasive procedures
with safety.
• If platelet transfusions are administered before a
procedure, it is critical that a posttransfusion
platelet count be obtained to prove that the de-
sired platelet count has been reached.
• Platelet transfusions should also be available on
short notice in case intraoperative or postopera-
tive bleeding occurs.
The indications for platelet transfusions in children
(or even in adults) with thrombocytopenia caused by
factors other than decreased platelet production have
not been well studied. Thus, as for RBC transfusion,
indications are based mainly on expert opinion. Sur-
gical interventions or invasive procedures in children
with idiopathic thrombocytopenia purpura or congen-
ital platelet disorders should be undertaken only in
consultation with a hematologist familiar with these
disorders. Prophylactic platelet transfusion is usually
ineffective in patients with idiopathic thrombocytope-
nia purpura.
Thrombocytopenia may be associated with massive
transfusion. Depending on the underlying pathologic
changes, the thrombocytopenia may be simply dilu-
tional (ie, caused by platelet loss through hemorrhage
and transfusion therapy with platelet-poor products),
or there may be additional factors (eg, disseminated
intravascular coagulopathy, hypoxia, and/or sepsis)
leading to accelerated platelet consumption.
In the absence of specific studies addressing the in-
dications for platelet transfusion in pediatric patients
in the setting of massive transfusion, it is reasonable to
apply the 1996 ASA guidelines.30 In this setting, these
guidelines state the following:
• Surgical and obstetric patients with microvascular
bleeding usually require platelet transfusions if
the platelet count is less than 50 × 109/L; with
intermediate platelet counts (50–100 × 109/L), the
determination (of whether the patient requires
platelet transfusion therapy) should be based on
the patient’s risk for more significant bleeding.
• Under normal circumstances, platelet counts
should be obtained to determine the need for plate-
let transfusions; in unusual situations, massively
transfused patients with microvascular bleeding
American Journal of Therapeutics (2002) 9(5)
HUME AND LIMOGES
suspected to be secondary to platelet deficiency
may benefit from empiric platelet transfusion.
Dosage and administration
Platelets possess both intrinsic and extrinsically ab-
sorbed A and/or B antigens. Nevertheless, ABO-
incompatible platelets (ie, platelets with A and/or B
antigens given to a recipient with a corresponding
natural A or B antibody) are usually clinically effec-
tive. Conversely, there are reports of acute intravascu-
lar hemolysis after the transfusion of platelet concen-
trates containing donor A and/or B antibodies incom-
patible with the recipient’s RBCs.38–41 It would thus
seem prudent, particularly in small children, where
the volume of plasma may be relatively large with
respect to the patient’s total blood volume, to use
ABO-matched platelets. If these are not available,
plasma compatible with the recipient’s RBCs should
be chosen. If this is also not possible, for infants and
young children, the plasma should be removed, or units
with low titers of anti-A or anti-B should be selected.
Platelets do not carry RhD antigens; however, the
quantity of RBCs in platelet concentrates is sufficient
to induce RhD sensitization even in immunosup-
pressed cancer patients. RhD sensitization caused by
platelet transfusions in RhD-negative patients can be
prevented by the administration of RhD immunopro-
phylaxis. Thus, if platelets from an RhD-positive do-
nor or platelets from a donor of unknown RhD phe-
notype are given to an RhD-negative recipient, admin-
istration of RhD immunoprophylaxis should be
considered, especially for female patients.37
A suitable starting platelet dose that can be expected
to raise the platelet level by 50 × 109/L is one platelet
concentrate per 10 kg of body weight. Platelet concen-
trates may be pooled before administration or infused
individually. An equivalent dose for apheresis plate-
lets is approximately 5 mL/kg. Patients with increased
platelet consumption (eg, with septicemia or dissemi-
nated intravascular coagulopathy) or splenomegaly
may require larger amounts of platelets.
Platelets may be volume reduced before infusion.
This extra manipulation leads to platelet loss, and if
not carefully performed, it may potentially adversely
affect platelet function and/or be a cause of bacterial
contamination. Volume reduction should therefore be
limited to patients who require severe volume restric-
tion or to situations where ABO-incompatible platelets
are the only available units for a neonate or child.
FRESH-FROZEN PLASMA
The indications and contraindications for the transfu-
sion of FFP are essentially the same for children as for
PERIOPERATIVE BLOOD TRANSFUSION THERAPY IN PEDIATRIC PATIENTS
adults. Hence, the guidelines recommended by the
ASA and the CMA are applicable.
Plasma should be ABO compatible with the recipi-
ent’s RBCs (ie, it should not contain antibodies that
could react with recipient A and/or B antigens). Usu-
ally, the RhD group need not be considered. When
large volumes of FFP are given to the RhD-negative
pediatric patients (or women of childbearing age),
however, prevention of RhD immunization by the use
of RhD immune globulin should be considered.
The dose of FFP in children is 10 to 20 mL/kg. This
dose usually raises the level of coagulation factors by
20% immediately after infusion. Posttransfusion moni-
toring of the patient’s coagulation status is important
for optimal treatment.
In summary the ASA and CMA guidelines recom-
mend that FFP be administered in the following settings:
1. For the emergency reversal of warfarin (ie, when
warfarin withdrawal and treatment with vitamin
K are inadequate)
2. For correction of microvascular bleeding in the
presence of significantly elevated prothrombin
time/partial thromboplastin time
3. For correction of microvascular bleeding in the
setting of massive transfusion when coagulation
tests cannot be obtained in a timely manner
With respect to the second indication, the plasma
concentration of each coagulation factor required for
hemostasis is around 0.20 to 0.25 U/mL, although for
Factor VII, the value is below 0.15 U/mL. These co-
agulation factor concentrations correspond to partial
thromboplastin time and prothrombin time values of
approximately 1.5 times normal. In both cases, the val-
ues are dependent on the reagents used. It is therefore
essential that the anesthesiologist be familiar with the
interpretation of coagulation tests as they are per-
formed at his/her institution.
Reference values for coagulation tests are essentially
identical for children older than 6 months and adults.
Nevertheless, the activated partial thromboplastin
time is often prolonged in the first 6 months of life
because of the lower concentrations of coagulation fac-
tors IX, X, and XI in newborns and young infants.
With respect to the contraindications for FFP, all
common congenital bleeding disorders can now be
treated with specific therapies and should not be
treated with either FFP or cryoprecipitate.
As discussed in many reviews and guideline docu-
ments over the past 10 to 15 years, FFP should not be
used solely for volume replacement. Albumin may be
used for replacement of large-volume losses, although
it is preferable to use a nonblood product whenever
possible. This has raised a question about the safety of
401
the use of starches (hetastarch [Hespan] and pen-
tastarch [Pentaspan]) for volume replacement in pedi-
atric patients. There are a few publications on the use
of hetastarch as a volume expander in pediatric pa-
tients.42–48 Except for allergic reactions, doses up to 20
mL/kg were well tolerated and do not seem to be
associated with coagulation abnormalities. Two addi-
tional studies describe the use of lower molecular-
weight hydroxyethyl starch solutions in a total of 38 in-
fants and children undergoing surgery.49,50 Again, the
starch solutions (exact volumes used were not stated)
seemed to be as efficacious as albumin, and no adverse
effects were observed. The total number of pediatric pa-
tients reported on in these studies is small, however, and
the package inserts for both Pentaspan and Hespan state
that the safety and efficacy of these products have not
been established in children.
Given concerns about the effects of starches on the
coagulation system and also possibly on renal func-
tion, pentastarch is not used for neonates or children
less than 2 years of age at our hospital.51,52 For older
children and adolescents, pentastarch is used in pref-
erence to albumin for volume expansion. The dosage
used is 28 mL/kg every 24 hours to a maximum of
2 L every 24 hours.
CRYOPRECIPITATE
The indications for the transfusion of cryoprecipitate
are also the same in children as in adults. Thus, the
ASA guidelines may be used in children, with the ex-
ception of the recommendation to use cryoprecipitate
to treat bleeding in patients with severe von Wille-
brand disease unresponsive to deamino-D-arginine
vasopressin. These patients (both children and adults)
are now treated with virally inactivated Factor VIII
concentrates rich in von Willebrand factor rather than
cryoprecipitate.
In children, the use of ABO-compatible units is pref-
erable. RhD group need not be considered. The num-
ber of units required is usually based on the amount
necessary to obtain a hemostatic level of fibrinogen
(ie, a fibrinogen level greater than 0.8–1.0 g/L). If the
units are carefully pooled, this can usually be accom-
plished by the transfusion of 1 U per 5 to 10 kg of
recipient weight.
DIRECTED DONATIONS AND
LIMITED-EXPOSURE BLOOD
DONOR PROGRAMS
A directed blood donation is one in which an indi-
vidual, at the request of a patient, or in the case of a
American Journal of Therapeutics (2002) 9(5)
402
child, a parent, donates blood that is reserved specifi-
cally for the subsequent transfusion of the requesting
patient. When parents wish to be directed donors for
their children or request other family members or
friends to do so, it is presumably because they believe
that blood from such donors is less likely to be a
source of transfusion-transmitted diseases than blood
from an anonymous volunteer blood donor pool.
Whether this is true has been a source of controversy
in the literature. Advocates of directed donations ar-
gue that such donors would not consider donating for
a loved one if they have known risk factors for trans-
fusion-transmitted diseases.53,54 Alternatively, others
argue that the absence of confidentiality that this situ-
ation entails and/or a strong desire to donate for the
given patient may discourage the directed donor from
being entirely truthful about his/her eligibility for
blood donation.
Studies addressing these questions would involve
the follow-up of large numbers of recipients of di-
rected blood donations over a long time and, conse-
quently, are unlikely to be performed. Instead of direct
studies, attempts have been made to estimate indi-
rectly the comparative safety of directed and standard
donor blood by measuring the frequency of positive
infectious disease markers in the two donor groups.
This approach is, of course, based on the assumption
that the risk of an undetected infectious unit is directly
related to the frequency of positive infectious markers
in the donor population under study. In three of four
studies, there were no statistically significant differ-
ences in the results of infectious disease markers in
directed donors versus anonymous volunteer donors,
whereas in one study, there was an increased fre-
quency of positive markers among directed donors,
which could probably be attributed to the relatively
larger number of first-time donors.55–58 From the point
of view of transfusion-transmitted viral diseases, di-
rected donors are therefore generally considered nei-
ther safer nor less safe than regular volunteer donors.
A potential risk of parental blood transfusion is chi-
merism and graft-versus-host disease (GVHD). For
patients of all ages (including adults), all cellular
blood components obtained from biologic relatives
must be irradiated before transfusion (see below). In
addition, as for autologous donations, it is possible that
the added complexity of providing directed donations
could lead to an increased frequency of errors.59
One situation in which directed blood donors may
actually provide an increased level of safety is a lim-
ited-donor blood program. For example, a single do-
nor can often provide all the RBC and/or plasma
needs of a small pediatric patient ineligible for autolo-
American Journal of Therapeutics (2002) 9(5)
HUME AND LIMOGES
gous donation who must undergo elective surgery for
which multiple blood units are normally required.60
TRANSFUSION-ASSOCIATED
GRAFT-VERSUS-HOST DISEASE
Transfusion-associated (TA) GVHD results from the
engraftment of immunocompetent donor T lympho-
cytes in a recipient whose immune system is unable to
reject them. Although it is possible that mild cases of
TA-GVHD may occur, TA-GVHD seems to be fatal in
at least 90% of cases. TA-GVHD can be prevented
by appropriate gamma-irradiation of cellular blood
products (ie, whole blood, RBCs, platelets, granulo-
cytes). Frozen products (ie, FFP, cryoprecipitate) do
not cause TA-GVHD.
Patients with congenital or acquired immunodefi-
ciency disorders (with the somewhat surprising ex-
ception of acquired immunodeficiency syndrome pa-
tients) are at risk for TA-GVHD. Cellular blood com-
ponents should be irradiated for all patients
undergoing hematopoietic stem cell transplantation.
There is debate about the necessity of irradiating
blood components for all adult cancer patients receiv-
ing chemo- and/or radiotherapy. However, most
pediatric centers do irradiate blood components for
these patients.
One situation in which transfusion may be required
before the presence of a congenital immunodeficiency
syndrome is suspected is in infants with the DiGeorge
anomaly. DiGeorge anomaly refers to the combina-
tion of thymic hypoplasia, parathyroid hypoplasia,
and cardiac defects, particularly conotruncal defects.
Unless a diagnosis of DiGeorge anomaly can be defi-
nitely ruled out, neonates and infants with these car-
diac defects should receive only irradiated cellular
blood components.
TA-GVHD may also occur in an immunocompetent
recipient if the recipient does not recognize the trans-
fused lymphocytes as foreign, as may occur when
there exists donor homozygosity for a human leuko-
cyte antigen haplotype for which the recipient is hap-
loidentical. The potential for the occurrence of this lat-
ter situation is the basis of the requirement to irradiate
directed donations from biologic relatives.
Generally accepted indications for gamma-
irradiation of cellular blood products in pediatric pa-
tients are given in Table 2. TA-GVHD in pediatric pa-
tients is reviewed in detail by Hume and Preiksaitis.61
Storage of RBCs after gamma-irradiation results in
an increase of supernatant potassium to a level of ap-
proximately twice that found in unirradiated units of
the same postcollection age. When initially reported,
PERIOPERATIVE BLOOD TRANSFUSION THERAPY IN PEDIATRIC PATIENTS
Table 2. Indications for use of gamma-irradiated blood
or blood components in pediatric patients over 4
months of age.
Known or suspected congenital cellular
immunodeficiency
Malignancy (hematologic or solid tumor) undergoing
chemotherapy or radiotherapy
Recipient of solid organ or hematopoietic stem cell
transplantation
Recipient of familial blood or HLA-matched cellular
products
this led to a debate concerning the need to routinely
wash irradiated RBC units intended for neonatal pa-
tients. These reports were meticulously reviewed by
Strauss,62 who concluded that such a practice is not
routinely necessary. In the situations discussed previ-
ously, where pediatric patients may be at risk for hy-
perkalemia after transfusion, the use of RBCs irradi-
ated before storage could potentially increase this risk.
Most pediatric transfusion services therefore try to ir-
radiate RBCs immediately before transfusion. If one
cannot avoid using RBC units irradiated before stor-
age, washing the RBCs to remove the supernatant
fluid should be considered in those situations with
other risk factors for hyperkalemia.
CYTOMEGALOVIRUS
LOW-RISK COMPONENTS
Cytomegalovirus (CMV) can be transmitted by cellu-
lar blood components. Blood components that have
been leukoreduced or are derived from CMV-
seronegative donors are at low (ie, less than 2%) risk of
transmitting CMV. In general, CMV low-risk compo-
nents are indicated for CMV-seronegative immuno-
suppressed patients or CMV-seronegative patients re-
ceiving a hematopoietic stem cell or solid organ trans-
plant from a CMV-seropositive donor. General
surgical patients, either adult or pediatric, do not re-
quire CMV low-risk components. Interested readers
are referred to recent reviews on transfusion-
transmitted CMV and its prevention.63–66
SUMMARY/CONCLUSION
In general, the approach to perioperative transfusion
therapy in children and adolescents is similar to that
used for young adults. There are a few differences,
however, especially for younger children, of which
403
anesthesiologists should be aware and which we have
highlighted in this review.
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