Pediatric Anesthesia 2005

15: 814830

doi:10.1111/j.1460-9592.2004.01549.x

Review article

Intraoperative pediatric blood transfusion therapy:

a review of common issues. Part II: transfusion
therapy, special considerations, and reduction of
allogenic blood transfusions
SANDRA L. BARCELONA MD*, ALEXIS A. THOMPSON
M D *
M D A N D C H A R LE S J . C O T E
Departments of *Anesthesiology and Pediatrics, The Feinberg School of Medicine at
Northwestern University, Chicago, IL, USA and Departments of Pediatric Anesthesiology
and Hematology-Oncology-Stem Cell Transplantation, Childrens Memorial Hospital,
Chicago, IL, USA

Keywords: blood transfusion: massive; coagulopathy; thrombocytopenia; recombinant factor seven (rFVIIa)

Introduction
Part two of this paper reviews transfusion therapy
with a focus upon massive blood transfusion, new
strategies for the treatment of massive transfusion
therapy, specific situations where transfusion may be
anticipated in pediatric patients, and a brief overview
for strategies to reduce allogenic blood transfusions.

III: Transfusion therapy

A. Massive blood transfusion and
coagulopathy
Massive blood transfusion is defined as the loss of
one or more circulating blood volumes. It is, therefore, important to calculate the patients estimated
blood volume (EBV) and to relate this to the volume
of blood products and other fluids administered
(Table 1). In addition the anesthesiologist should
estimate how much blood will be allowed to be lost
before the initiation of packed RBC transfusion. The
patients EBV is generally related in part to the
patients age as well as body habitus. Younger
Correspondence to: Sandra L. Barcelona, Department of Pediatric
Anesthesiology (Box 19), Childrens Memorial Hospital, 2300
Childrens Plaza, Chicago, IL 60614, USA (email: sandra.barcelona
@cmh.com).

814

patients have a higher fraction of their weight as

blood while more obese patients have a lower
fraction. Once the patients circulating blood volume
has been estimated then a further simple calculation
allows estimation of the maximal allowable blood
loss (MABL). A simple mathematical calculation is:
MABL

starting hematocrit
target hematocrit

starting hematocrit
 EBV

For example, if the child weighs 25 kg there will

be a circulating blood volume of 70 ml 25 kg
1750 ml. If that child also has a starting hematocrit
of 36% and the target hematocrit is 21% then the
following calculation applies:
36
21
 1750  730ml
36
This shed blood can be replaced with a balanced
salt solution such as lactated Ringers solution in a
volume of 3 : 1, i.e. 2200 ml or with 5% albumen
1 : 1 or hetastarch 1 : 1, i.e. 730 ml. Once the estimated blood loss reaches this target value then RBC cell
transfusion should be initiated. Obviously preterm
and term infants, children with cyanotic congenital
heart disease, large ventilation/perfusion mismatch,
high metabolic demand, and children with respiratory failure, may benefit from having the hematocrit
MABL

2005 Blackwell Publishing Ltd

Table 1
Estimated circulating blood volume versus age or weight
Age
Premature infant
Term infant 3 months
Children older than 3 months
Very obese children

Estimated blood volume (mlkg)1)

90100
8090
70
65

maintained at a higher target value. Conversely,

children in countries with poor blood product
screening may benefit from avoiding transfusion
until a much lower target hematocrit, e.g. 5 gdl)1.
Since the hematocrit in packed RBCs is approximately 70%, each 100 ml of packed RBCs transfused
will provide 70 ml of RBCs. In the example given
above, if the blood loss exceeded the MABL by
150 ml and assuming that the target hematocrit was
30%, then replacement would be made according to
the following formula:
(i) volume of blood to replace (150 ml) desired
hematocrit (30%) 45 ml of 100% RBCs;
(ii) the approximate hematocrit in packed RBCs is
70%;
(iii) therefore, 45 ml 0.70 approximately 65 ml
of packed RBCs;
(iv) 65 ml of packed RBCs (hematocrit 70%) is
equivalent to 150 ml of (whole) blood with a
hematocrit of 30%.
This can usually be simplified by transfusing
approximately 0.5 ml packed RBCs for each milliliter of blood loss beyond the MABL; this will result in
a slightly higher hematocrit than the target 30% but
since all of these calculations are estimates the end
result is usually close to the desired value.
The coagulopathy of massive blood transfusion is
caused by both a reduction in platelets (dilutional
thrombocytopenia) and a reduction in clotting factors. In general, a good rule of thumb is that a patient
will lose approximately 40% of the starting platelet
count with the first blood volume lost, another 20% of
the starting platelet count with the second blood
volume lost, and approximately 10% of the starting
platelet count with the third blood volume lost
(Figure 1) (1). Thus at three blood volumes lost with
no platelet replacement, the platelet count would be
expected to be reduced by approximately 70% from
baseline values (1). This emphasizes why it is so vital
to have a baseline platelet count when massive blood
loss is anticipated since patients who begin with a low

2005 Blackwell Publishing Ltd, Pediatric Anesthesia, 15, 814830

Percent change in platelet count from baseline

INTRAOPERATIVE BLOOD TRANSFUSION THERAPY

815

20

40

60

80

100
0.5

1.0

1.5

2.0

2.5

3.0

3.5

Blood volumes lost

Figure 1
Serial changes in platelet counts as a percent of baseline
(mean SD) in 26 children who lost one to three blood volumes
during surgery and did not receive exogenous platelets. Patients
whose platelet counts were 50 109 l)1 did not exhibit clinically
important bleeding [modified from (1)].

platelet count are at risk for pathological bleeding

even after only one blood volume loss whereas those
who start with an abnormally high platelet count
may not require transfusion despite blood loss equivalent to four or five circulating blood volumes (1).
The coagulopathy secondary to dilution of clotting
factors depends upon the type and volume of
transfused blood product. Whole blood contains all
clotting factors including fibrinogen at normal values except for the labile factors (FV and FVIII); even
these factors are present in 2050% of their normal
values. Therefore with transfusion of whole blood,
despite reduced amounts of the labile clotting factors
(FV and FVIII), pathological coagulation generally
does not occur until three or more blood volumes
have been lost (24). However, such large quantities
of whole blood are rarely used with modern blood
banking, instead the blood loss is replaced with
albumen, starch, crystalloid, and packed RBCs. With
this type of replacement multiple clotting factor
deficiencies will appear much earlier since approximately 80% of the coagulation factors have been
separated into the plasma fraction. In this situation,
clotting factor deficiency should be anticipated once
blood loss exceeds one blood volume (Table 2).
The evaluation of coagulopathy depends in part on
the availability of specific laboratory tests that can be
rapidly returned to the anesthesiologist so as to allow
the intraoperative evaluation of specific abnormalities of coagulation. The simplest approach, when

8 16

S.L. BARCELONA ET AL.

Table 2
Changes in prothrombin (PT) and partial thromboplastin (PTT)
times during massive blood transfusions in children receiving
either packed RBCs and albumen or packed RBCs and crystalloid
(66)
Blood volumes lost
Prothrombin time
n
Mean SD
Range

Baseline

0.5

0.75

1.0

26
16
12
10
10.9 0.96 12.5 0.77 13.2 0.76 13.6 0.98
9.3 12.0 11.4 14.0 11.4 14.2 11.9 15.8

Partial thromboplastin time

Mean SD
31.8 4.4 38.0 4.9
Range
25 45.9 28.1 59.6

40 5.4 45.1 13.1

33 51.5 25.6 60

laboratory tests are slow to return or unavailable, is

simply drawing a sample of blood into a blood tube
without anticoagulant and observing the rapidity of
clot formation and the presence or absence of clot
lysis. A clot should form in 48 min and there should
be no clot lysis if all coagulation parameters are
within normal limits and there is no coagulopathy. A
platelet count will provide a reference number to
indicate the need to increase platelets via transfusion
therapy. Generally, in a normal patient a platelet
count >50 000 mm)3 does not require treatment
unless further blood loss is expected. Obviously
cardiac bypass is a different situation where platelets
become dysfunctional due to the trauma of the
bypass machine. A prothrombin time (PT) will
provide global information regarding the so called
extrinsic clotting system (factors VII, X, V, prothrombin and fibrinogen); an acceptable value would be an
INR of <1.5 (less than 1.5 times normal). An activated
partial thromboplastin time (PTT) provides global
information regarding the so-called intrinsic clotting
system (factors XII, XI, IX, VIII, X, V, prothrombin and
fibrinogen); a value <50 s (less than 1.5 times normal)
does not generally require treatment. The presence of
a significant increase in fibrin split products combined with a low fibrinogen value generally indicates
disseminated intravascular coagulopathy. In this
situation, cryoprecipitate or fresh frozen plasma
may provide the needed increase in factors. More
sophisticated tests such as the platelet function
analyzer (PFA) will provide a measure of platelet
function that is more reliable than bleeding times in
children. Thromboelastography (TEG) will provide
information regarding the rapidity of clot formation
and clot lysis as well as a rapid means for determining the effectiveness of each intervention. Neither

PFA nor TEG have been found to have a positive

predictive value for perioperative bleeding in most
settings. Management of specific coagulation abnormalities such as hemophilia and von Willebrand
disease are beyond the scope of this review but new
approaches to coagulation are presented below.
Table 3 presents our indications for monitoring
based upon the anticipated blood loss. Recent advances in transfusion therapy such as the development of
recombinant clotting factor replacement therapy may
dramatically alter our current approach to patients
undergoing massive blood transfusions resulting
in either dilutional thrombocytopenia or multiple
clotting factor deficiencies. Such therapy will allow
specific clotting factor replacement and reduce exposure to homologous blood products and the potential
for disease transmission or transfusion reactions.

B. Recombinant factor VIIa

A novel but at present enormously expensive
approach to treat bleeding is the use of recombinant
factor VIIa (rFVIIa) (NovoSeven, Novo Nordisk
Pharmaceutical Inc., Princeton, NJ, USA). This product was developed for the management of bleeding
complications in hemophilia patients who also have
alloantibodies against factors VIII and IX (58).
However, it is likely that further research will find
many additional indications for patients with coagulopathy from a variety of causes (Figure 2) (9). The
current model of the coagulation cascade is based
upon the observation that formation of a tissue
factor-factor VIIa complex (TF-FVIIa) is the major
initiating event of in vivo hemostasis (Figure 3). This
paradigm differs from the traditional coagulation
cascade involving separate intrinsic and extrinsic
pathways and helps to explain the importance of the
presence of adequate amounts of critical factors (i.e.
VII, X, V, VIII and XI) while deficiencies of others
(i.e. XII) do not result in clinical bleeding. Tissue
factor is normally located deep within vessel walls
and is not usually exposed to the general circulation
until an injury occurs. Injury to tissue results in
release of TF from the endothelium. Tissue factor
then forms a complex with activated factor VII
(VII VIIa). Factor VIIa in turn activates factor X
(X Xa) and prothrombin, which promotes the
production of thrombin and the formation of fibrin
clots at the site of injury (10). It appears that rFVIIa

2005 Blackwell Publishing Ltd, Pediatric Anesthesia, 15, 814830

INTRAOPERATIVE BLOOD TRANSFUSION THERAPY

Table 3
Estimated predicted blood loss
and recommended monitoring
and equipment

Predicted blood loss

817

Recommended monitors/equipment

<0.5 blood volumes

0.51.0 blood volumes
1.0 blood volumes or greater
1.0 blood volumes or greater
with potential for rapid blood loss
Severe head injury
Major trauma with unknown severity

Routine monitoring
Routing monitoring + urine catheter
Routine monitoring + urine catheter
+ CVP + arterial line
Routine monitoring + urine catheter
+ CVP + arterial line + large bore IV
+ rapid infusion device
Routine monitoring + urine catheter
+ CVP + arterial line + large bore IV
Routine monitoring + urine catheter
+ CVP + arterial line + large bore IV
+ rapid infusion device

Modified from Cote CJ, Dsida RM. Strategies for blood product management and transfusion
reduction, In: A Practice of Anesthesia for Infants and Children, 3rd edn. Philadelphia, PA: WB
Saunders Co., 2001.

Single
factor

Figure 2
Proposed likely indications for
the use of recombinant factor VIIa
(NovoSeven). Note that this
agent is not yet approved for use
in children except for the treatment of hemophilia von Willebrand disease with high titer
inhibitors or for congenital factor
VII deficiency. However many
clinical trials in adults and anecdotal reports in children suggest
potential use for a wide variety of
conditions resulting in pathological bleeding. See text for
details. Modified from (9).

Multiple
clotting
factors

Defective
platelet
function

Factor
deficiency

Low
platelet
count

Platelet
disorder

rVIIa
GI

CNS

also activates factors IX and X on the surface of

activated platelets (IX IXa & X Xa), leading
to the generation of additional amounts of thrombin
(1117). Activated platelets serve as a surface site for
activation of factors VIII (VIII VIIIa), and XIa, as
well as further interaction with activated factors X
and V (V Va) to create thrombin. Effective
hemostasis requires full thrombin generation in the
presence of activated platelets. Thus rVIIa administration promotes hemostasis at several locations
within the coagulation cascade and may be useful
in normal patients as well as patients with thrombocytopenia (1820).
The pharmacokinetics of rFVIIa have been most
extensively studied in patients with hemophilia. It

2005 Blackwell Publishing Ltd, Pediatric Anesthesia, 15, 814830

General
hemostasis
Acute
bleeding

Massive
transfusion
Surgical
bleeding

Postbypass

is important to note that the half-life of rFVIIa is

shorter (1.3 vs. 2.7 h) and the clearance faster (67
vs. 37 mlkg)1h)1) in pediatric patients compared
with adults (21). There may also be differences in
patients who have ongoing blood loss compared
with hemophilia patients (21). Studies of small
numbers of cirrhotic patients and those undergoing
liver transplant have revealed altered pharmacokinetics as well (21). Initial dosing regimens for
hemophiliacs undergoing surgery include an intravenous dose of 90120 lgkg)1 of rFVIIa (22).
Studies completed in trauma and surgical patients
have used somewhat higher dosing (up to
200 lgkg)1) (23). Follow-up dosing intervals of 2
4 h because of the relatively short circulating half

8 18

S.L. BARCELONA ET AL.

VASCULAR INJURY
VII
TF exposure

VIIa + TF

Prothrombin

IX
VWF-FVIII

Xa + Va
THROMBIN

Platelet activation

VIIIa + IXa

Fibrinogen

Fibrin

Clot
formation

Figure 3
Schematic diagram of current model of the coagulation cascade. Hemostasis is initiated following tissue factor (TF) release and activation of
factor VII (FVIIa). FVIIa mediates coagulation through the generation of thrombin, activation of factor X (FXa), and activation of factor IX
(FIXa). Activation of factors V, VIII, and IX occurs on the surface of activated platelets in response to thrombin generation.

life of NovoSeven, adds considerably to the expense of using this agent.

Satisfactory hemostasis with rFVIIa administration has been achieved in critically ill massively
transfused trauma victims, patients undergoing
cardiopulmonary bypass, those sustaining liver
injury or undergoing liver transplantation, as well
as uncontrolled gastrointestinal or intraabdominal
hemorrhage (16, 2432). Neurosurgical patients with
coagulopathy have also received benefit from rFVIIa
administration in order to correct coagulopathy
prior to surgical intervention to evacuate intracranial
bleeding (33).
The use of rFVIIa has been shown in adults to
decrease prothrombin time and increase hemostasis
at the site of injury (3436). The sensitivity of plasma
assays such as the prothrombin time (PT) to even the
smallest quantities of activated factor VII do not
correlate with clinical outcomes and thus makes
these tests unsuitable for monitoring responses to
rFVIIa therapy (37). A more promising strategy has
been the use of TEG. These whole blood assays
measure several aspects of effective hemostasis,
including the rate of thrombin generation, as well

as fibrin clot strength, elasticity and degradation in

the presence of activated platelets (3840). This
approach has been far more reliable in measuring
responses to rFVIIa in hemophilia patients with
high-titer factor VIII inhibitors, in normal subjects,
and has also been used for monitoring anticoagulation therapy.
The administration of rFVIIa provides the advantage of hemostasis at the site of injury, without
systemic activation of the coagulation cascade (11
16, 41). Although rFVIIa has proven useful in
multiple situations, at the time of this writing, it is
not United States Food and Drug Administration
(FDA) approved for use in trauma or surgical
procedures. The initial intention and only FDA
approved use is for patients with hemophilia or
von Willebrand disease who have developed inhibitor antibodies or patients with congenital factor VII
deficiency. There are limited pediatric data at this
point but anecdotal cases suggest some promise for
treating a variety of conditions with pathological
bleeding (27, 33, 4251). Because rFVIIa uses recombinant technology, no material of human origin or
blood product is used in its production (17). It,

2005 Blackwell Publishing Ltd, Pediatric Anesthesia, 15, 814830

INTRAOPERATIVE BLOOD TRANSFUSION THERAPY

therefore, may aid in the control of surgical bleeding

in Jehovahs Witness patients and help to avoid
transfusion. It also is less immunogenic and eliminates the risk of viral or bacterial contamination that
can occur with blood product transfusion. It would
appear that this new weapon for treating coagulopathy will be available to anesthesiologists in the near
future. It is also likely that the cost of such treatment
will be quite enormous thus mandating very clear
indications. Potential concerns regarding the recombinant products are allergic reactions, inhibitor
formation, and thromboses (6).

C. Platelet infusions
In general, most pediatric patients will have platelet
counts within the normal range at the time surgery is
needed, however, those with chronic inflammatory
diseases and patients with functional or surgical
asplenia may have high platelet counts. Patients
with infections, on myelosuppressive chemotherapy,
or those with ongoing coagulopathies will be at
risk for thrombocytopenia. For patients who are
otherwise normal, a platelet count greater than
50 000 mm)3 is required in order to maintain hemostasis (1). Patients who are chronically thrombocytopenic will often not manifest bleeding
tendencies even when the platelet count is in the
10 00020 000 mm)3 range. Immune or nonimmunological-based peripheral platelet destruction may
shorten the survival of transfused platelets. Nonetheless, perioperative platelet transfusions may be
appropriate if significant bleeding is anticipated. In
these patients a preoperative transfusion plan
should be developed in consultation with the childs
oncologist/hematologist.

IV: Specific circumstances

A. Trauma
Trauma related injuries are the leading cause of
death in pediatric patients. Exsanguination, either at
the site of the accident, or in the hospital, accounts
for 39% of all traumatic deaths (52). The major
source of morbidity and mortality in pediatric
trauma victims is oxygen deprivation to vital organs.
Because both anemia and hypovolemia decrease
oxygen delivery, appropriate transfusion and

2005 Blackwell Publishing Ltd, Pediatric Anesthesia, 15, 814830

819

volume resuscitation are critical. Although rapid

infusion of fluids to a trauma patient who is
hemorrhagic and hypotensive may seem obvious,
the end points for fluid administration to hemodynamically stable victims of blunt trauma and severe
head injury are vague and not well established. The
overtransfusion of such patients may result in
cerebral edema, pulmonary edema, or coagulopathy.
The evaluation and treatment of the pediatric
trauma patient differs from that of the adult primarily because of differences in physiology. The evaluation of the volume status of the pediatric trauma
patient may be difficult since children are able to
maintain a normal blood pressure in a supine
condition with a loss of up to 20% of their blood
volume. In pediatric trauma victims, postural hypotension and a narrow pulse pressure may be more
sensitive signs of hypovolemia than tachycardia or
systolic hypotension. Invasive monitors can be
extremely helpful in this population, and should
never be omitted secondary to patient size. The
insertion of an arterial line greatly facilitates beat to
beat blood pressure monitoring while a central
venous line provides valuable information regarding
cardiac filling pressures particularly when the blood
loss is such that it cannot be quantitated, e.g. internal
bleeding, neurosurgical trauma. Our experience has
been that a 23 mmHg reduction in the central
venous pressure may reflect the loss of as much as
20% of the circulating blood volume. Likewise a
diminished arterial pulse contour (loss or migration
of the dicrotic notch) may identify hypovolemia that
would not be recognized by vital signs alone (53).
Metabolic acidosis secondary to hypoperfusion and
low or concentrated urine output are additional
indicators of hypovolemia. Proper assessment of
volume status aids interpretation of obtained hemoglobin levels. A volume depleted child may have a
normal hemoglobin value. Once volume resuscitated, however, a more realistic lower hemoglobin
level may reveal significant anemia.
Like adults, large amounts of blood may be lost
internally secondary to a long bone fracture, retroperitoneal bleeding or blunt abdominal trauma.
Unique to the child is the potential for substantial
bleeding from closed head trauma. Infants and
toddlers have open cranial sutures which allows
for collection of a substantial amount of intracranial
blood. Young pediatric patients may suffer from

8 20

S.L. BARCELONA ET AL.

hemorrhagic shock secondary to closed head injury,

while older children and adults are unlikely to
encounter this result.
Volume resuscitation should be initiated with
large bore intravenous access. It may be difficult to
access peripheral veins in a hypovolemic child.
Short length, thin walled catheters have been
successfully placed in the femoral or antecubital
veins of dehydrated pediatric patients (54). The
intraosseous route of fluid delivery may be life
saving for delivery of fluids, medications, and
dilute blood products when intravenous access
cannot be obtained (5557).
The efficacy of colloid administration instead of
crystalloid has been debated for many years. Hypertonic saline and dextran solutions have been demonstrated to increase survival in hypotensive patients
with severe head injury as well as patients with
penetrating trauma when compared with standard
resuscitation with normal saline (58, 59). However,
no randomized controlled studies of pediatric
patients have been published. In addition hypertonic
saline/dextran solutions as well as hydroxyethyl
starch are potential causes of coagulopathy in
trauma patients (60). These solutions appear to
compromise clotting by interfering with factor VIII
as well as von Willebrand factor, resulting in a von
Willebrand syndrome (61, 62).
The severely injured child may require massive
blood transfusion. The metabolic consequences of
massive transfusion including hypothermia, hyperkalemia, hypocalcemia, and hypomagnesemia are
discussed in part I. Coagulopathy is also more likely
to develop in a massively transfused child who has
suffered from hypoperfusion or hypothermia (63).
Although dilutional thrombocytopenia has been
labeled as the primary reason for coagulopathy in
the massively transfused patient, most studies demonstrating this point were carried out using whole
blood (4, 64). Since most transfusion therapy, especially in the trauma patient, is now administered as
packed RBCs, dilution of clotting factors may be an
equally important cause of coagulopathy. In fact, the
dilution of clotting factors has been demonstrated to
become clinically important (with PT and PTT
approaching 1.52 times normal levels) when 1.5
blood volumes have been transfused (Table 2) (65
67). On the other hand, platelet counts which begin
as normal (>150 000 mm)3) are unlikely to be the

cause of clinically significant coagulopathy until

more than two blood volumes have been transfused
(Figure 1) (1).

B. Neonates
Neonates pose some unique challenges with respect
to anesthesia and blood products. One potential
complication of RBC transfusion that occurs less
frequently in neonates compared with older children
and adults is a major hemolytic reaction. For the first
34 months of life, infants are unable to form alloantibodies to RBC antigens (6870). After initial
screening for ABO/Rh determination, repeated
screening for antibodies is generally not necessary.
With the exception of exposure to the Rh-D antigen,
hemolytic reactions due to ABO incompatibility
rarely occur in young infants because of their immature immune systems. Therefore, administration of
RBCs to infants less than 4 months of age may be
either type specific or O negative and do not require
further cross matching. Beyond the first 4 months of
life, hemolytic reactions remain an important cause
of transfusion related morbidity and mortality.
Premature infants may be more susceptible to
hypocalcemia hypothermia with large volume blood
transfusions. As noted previously, transfusion-related graft versus host disease occurs more often in sick
neonates and may require special consideration for
the use of directed donor components from close
relatives (pretransfusion irradiation) (69, 71, 72).
Filtration to leukocyte-deplete blood products prior
to transfusions should be routine in neonates and is
likely to reduce the incidence of febrile nonhemolytic transfusion reactions, transmission of CMV
infection, as well as transfusion-mediated immunomodulation.

C. Cardiac surgery
Children are prone to more hemostatic disturbances
after cardiopulmonary bypass (CPB) than adults.
Children with cyanotic congenital heart lesions are
at high risk for hypoxemia and resulting polycythemia. Hypoxemia prolongs bleeding times by negatively affecting platelet function. Patients with
congenital heart disease have also demonstrated a
high incidence (19%) of abnormal preoperative PT
and PTT values, as well as abnormalities in von

2005 Blackwell Publishing Ltd, Pediatric Anesthesia, 15, 814830

INTRAOPERATIVE BLOOD TRANSFUSION THERAPY

Willebrand factor (73, 74). Decreased clotting factor

production may be caused by hepatic congestion
secondary to heart failure. Disseminated intravascular coagulopathy may consume clotting proteins as
well. Multiple factors, which may be identified
preoperatively, contribute to these patients
increased risk for perioperative bleeding.
Neonates are at highest risk for increased bleeding
after cardiac surgery in part because of immaturity
of the coagulation system (75, 76). In addition, many
newborns undergo complex repairs that require
longer cardiopulmonary bypass (CPB) times, deep
hypothermia, or circulatory arrest, all of which have
been demonstrated to result in increased perioperative bleeding (7679); the risk of perioperative
bleeding increases with decreasing patient age.
The relatively large volume of CPB pump prime
significantly dilutes the small childs clotting factor
and platelet levels. Modern CPB pumps use much
smaller volumes and are less likely to contribute to
coagulopathy due to hemodilution (80). Ultrafiltration of the blood remaining in the CPB circuit helps
to increase the patients hemoglobin as well as
maintain high levels of clotting factors and platelet
numbers (81, 82). Alternatively, intraoperative
hemodilution by removing whole blood from the
patient to be given after CPB as well as bloodless
priming of the CPB pump have successfully limited
patients exposure to homologous blood components after cardiac surgery (8388). Prebypass
removal of blood for later transfusion should preserve platelet function by eliminating the exposure
of the platelets to the damaging effects of the bypass
machine while also providing replacement of clotting factors. This technique is limited to larger
pediatric patients. Intraoperative blood salvage (i.e.
cell saver) may also be utilized in these patients,
however, ultrafiltration yields higher levels of functional platelets and clotting factors (8588).
Aprotinin, a serine protease inhibitor, prevents
fibrinolysis and platelet activation normally seen
after CPB (8991). When given by high dose regimen, it decreases blood loss in pediatric cardiac
patients undergoing complex surgery or resternotomy (92). In addition to its hemostatic benefits,
aprotinin has also been linked to improved postoperative oxygenation resulting in less postoperative
ventilation time (89). This may be attributed to its
systemic anti-inflammatory effects. Some studies

2005 Blackwell Publishing Ltd, Pediatric Anesthesia, 15, 814830

821

demonstrated no benefit of aprotinin in children

(93), and raised concerns regarding allergic potential
and renal impairment (9496). However, other studies have found a low risk to benefit ratio and
reduced cost with the use of high dose aprotinin in
this pediatric surgical population (89, 92, 94, 9799).
The risk of allergic reaction upon secondary exposure to aprotinin in the pediatric population is less
than half that of adults (1.2% vs. 2.7%) (100). To
further lessen this incidence, the time between
aprotinin exposures is recommended to be greater
than 6 months (101). In high risk patients, a test dose
of 10 000 KIU should be given when surgeons are
prepared to initiate bypass quickly, and preemptive
histamine blockade should be considered (101).

D. Tonsillectomy and adenoidectomy

Tonsillectomy is one of the most common pediatric
surgical procedures. Although perioperative transfusion is rare, the procedure carries potential for
life threatening hemorrhage. The majority of early
bleeding episodes occur within the first 46 h after
the procedure (102105). Late bleeding typically
occurs 510 days postoperatively (102105). Late
bleeding is commonly associated with an episode
of early bleeding (104). In either situation, a
significant amount of blood may be swallowed by
the child, which makes assessment of its severity
difficult. The child who is hypovolemic from
decreased oral intake secondary to pain may have
an artificially elevated hematocrit. Careful assessment of the patients volume status and laboratory
values are imperative to a proper evaluation and
preparation for reoperation. Blood pressure and
heart rate determination in both the supine
and sitting position may shed light upon the childs
intravascular volume status.
No universal practice of preoperative screening
for increased risk of bleeding has been adopted by
all otolaryngologists. Multiple studies have demonstrated that neither preoperative bleeding history
nor routine laboratory screening with PT, PTT, and
bleeding time are reliable predictors of postoperative
bleeding (106109). However, laboratory screening
may be useful in patients who have a history
suggestive of a major bleeding disorder. Even in
these individuals, screening tests such as the PT and
PTT may fail to identify some patients with bleeding

8 22

S.L. BARCELONA ET AL.

tendencies. The platelet function analyzer (PFA) is a

relatively new tool which simulates primary hemostasis and is particularly well suited for evaluating
suspected cases of von Willebrands disease or
intrinsic platelet defects (110, 111). More formal
consultation with a hematologist is strongly recommended to determine the most appropriate course of
preparation for surgery. For example, patients with
the most common type of von Willebrand disease
can undergo successful, nonhemorrhagic adenotonsillar surgery if treated appropriately with DDAVP
[desmopressin (1-deamino-8-D-arginine vasopressin)]. Other subtypes, however require the use of
cryoprecipitate or plasma-derived factor VIII concentrate containing von Willebrand factor (112).
Bleeding in patients with intrinsic platelet defects
can be prevented or controlled with platelet transfusions. Without proper family and patient history
and subsequent testing, these patients may not be
identified preoperatively and may suffer from
marked, uncontrollable bleeding. It appears that
meticulous surgical technique is the most important
factor assuring that postoperative hemostasis is
maintained regardless of the patients history.
The use of ketorolac for postoperative pain control
in tonsillectomy patients has been debated in the
literature. Although an effective analgesic, concerns
regarding its antiplatelet activity have limited its
use. Several studies have demonstrated increased
perioperative bleeding associated with ketorolac use
for analgesia following tonsillectomy, however,
none identify the need for further intervention in
these patients (113117). Ketorolac has been demonstrated to lower pain scores when compared with
placebo (118). It is unclear whether or not ketorolac
use changes clinical outcome in the pediatric adenotonsillar surgery population. However, because of
its theoretical risk of inhibiting platelet function, it is
prudent to reserve its use until after the surgery has
been completed and hemostasis obtained. After
initial hemostasis has been obtained, the influence
of platelet function upon subsequent hemorrhage
should be less (119). The next generation of cox-2
inhibitors will not have this antiplatelet effect and
should provide analgesia without respiratory
depression or the potential for bleeding. However,
other methods of pain control have been shown to be
equally efficacious without the potential risk for
increased bleeding (114, 115, 117).

E. Orthopedics
The vast majority of pediatric orthopedic procedures
are accomplished without the need for blood transfusions. However, the inability to use a surgical
tourniquet (such as femoral osteotomy or spinal
fusion cases) can result in clinically important blood
loss. The incidence and severity of the blood loss is
often dependent upon the skills of the surgeon. A
number of techniques such as hemodilution and
controlled hypotension have been advocated to
reduce the exposure to exogenous blood products,
however concerns for impaired spinal cord blood
flow during spinal instrumentation have altered our
practice. We no longer advocate combined controlled hypotension and extreme hemodilution. If
we reduce blood pressure it is only reduced to a
modest range (mean arterial pressure 6575 mmHg)
and we generally do not allow the hemoglobin to fall
below 8 gdl)1. If the patient develops abnormal
bleeding in an early part of the procedure it is vital
to check the patients position to assure that the
support bolsters have not changed position resulting
in increased intraabdominal pressure thereby
increasing venous pressure by mechanical obstruction.
One further concern is that after major spine
fusion procedures there may be the potential for
continued bleeding from the raw surfaces of bone;
therefore, it is our practice to transfuse these patients
so that their hemoglobin at the end of surgery is in
the 1011 gdl)1 range. The use of aprotinin, epsilon
aminocaproic acid, tranexamic acid, or DDAVP has
failed to consistently demonstrate decreased blood
loss (120).

F. Neurosurgery
One study has demonstrated that pediatric patients
undergoing neurosurgical procedures may have a
hypercoagulable state postoperatively as demonstrated by TEG (121). However, the primary cause of
problems related to hemostasis in neurosurgical
procedures are attributable to massive blood loss
and subsequent dilutional coagulopathy or disseminated intravascular coagulopathy (DIC). Neural
tissue injury due to trauma can also result in tissue
thromboplastin release and subsequent activation
of the coagulation cascade via FVIIa. Children

2005 Blackwell Publishing Ltd, Pediatric Anesthesia, 15, 814830

INTRAOPERATIVE BLOOD TRANSFUSION THERAPY

undergoing resection of vascular malformations and

vascular tumors (e.g. choroid plexus adenoma) as
well as trauma patients with epidural or subdural
hematomas are at great risk for massive and rapid
blood loss. Children with traumatic brain injury and
shaken baby syndrome are at particular risk for the
development of DIC. In each of these cases it is
prudent for the clinician to use invasive monitoring
(arterial and central venous monitoring) as well as
large bore intravenous catheters with appropriate
blood warming devices (see part I). It is rare for
children undergoing elective resection of brain
tumor to develop a coagulopathy unless it is due
to dilution of clotting factors.

G. Burns
Children with burn injuries can develop a variety of
clotting factor abnormalities. These abnormalities
depend in part upon the extent of the burn injury,
the presence or absence of sepsis, and the volume of
blood shed during reconstructive surgery. Early
after massive burn injury there is both a consumptive coagulopathy and a microangiopathic hemolytic
process (122, 123). Thus anemia, thrombocytopenia,
and evidence of coagulopathy are common. After
the initial 35 days following burn injury the typical
anti-inflammatory response occurs and patients
develop marked increases in fibrinogen, platelets,
as well as a variety of clotting factors (122124).
Platelet counts over 1000 000 mm)3 and fibrinogen
values over 2 gdl)1 may be observed. Despite these
abnormalities it is rare for pediatric burn victims to
suffer thrombotic events. Conversely with the onset
of sepsis there may be a sudden fall in the platelet
count. Excision of burn wounds can also involve
rapid and massive blood loss; some of this blood loss
may be reduced by using saline with dilute concentrations of epinephrine injected under both the
donor and recipient sites (clysis) (125). In addition,
because the skin has been damaged it no longer
provides the normal insulation to the body such that
these patients are particularly prone to hypothermia.
Thus, although uncomfortable, it is wise to use a
very warm operating room (35C). The administration of blood products should be guided by serial
platelet counts and evaluation of the PT and PTT
(66). In general, abnormal bleeding does not occur if
the platelet count is maintained above 50 000 mm)3

2005 Blackwell Publishing Ltd, Pediatric Anesthesia, 15, 814830

823

(1). It should also be kept in mind that central

venous lines, especially those with multiple ports,
will be inadequate to rapidly administer RBCs since
there is so much resistance (126). Short-term femoral
venous catheterization for the procedure with a
large bore short catheter provides a better means for
rapid RBC transfusion.

H. Kidney transplantation
Patients with renal failure have anemia for multiple
reasons. As kidney failure progresses, erythropoietin
production decreases, red blood cell life span shortens secondary to hemolysis from circulating toxins,
and iron and folic acid deficiencies ensue (127). In
addition, hemodialysis increases the severity of
anemia secondary to chronic blood loss within the
dialysis circuit and progressive reduction in erythropoietin levels compared with peritoneal dialysis
(128). Nevertheless, this anemia (typical hematocrit
25%) is chronic, and therefore, generally well tolerated if the patient is euvolemic. The threshold for
preoperative transfusion of these patients should be
lower than for the general population in whom
perioperative anemia is more likely to be acute and
less well tolerated. Historically, blood transfusion
was performed pretransplant for the purpose of
inducing immunosuppression. With the advent of
more controlled medical immunosuppressive therapy (e.g. cyclosporin), the practice of automatic
pretransplant transfusion of these patients has
mostly fallen out of favor. In fact, there is some
evidence that blood transfusion to pediatric transplant recipients may actually be contributory to the
increased incidence of rejection in this population
(129). Alternatively, recombinant erythropoietin [Epogen (rhEPO), Amgen, Inc., Thousand Oaks, CA,
USA] has successfully increased hemoglobin levels
of pediatric renal failure patients over a period of a
few months (128). Erythropoietin therapy may aid in
increasing the patients oxygen carrying capacity if
begun enough in advance of a planned renal
transplant (e.g. a living donor).
Patients with renal failure are at increased risk for
platelet dysfunction secondary to uremia thereby
increasing bleeding tendencies. Although thrombocytopenia is not uncommon, platelet dysfunction
appears to be more problematic. There are multiple
causes of platelet dysfunction in this population,

8 24

S.L. BARCELONA ET AL.

some of which can be at least partially treated with

dialysis (130, 131). Platelet transfusion as well as
DDAVP may be helpful in the patient with a
continued prolonged bleeding time despite dialysis
(132).
Pediatric renal transplants differ from those of
adults intraoperatively secondary to size discrepancies between donor organ and recipient. It is common for small pediatric patients to receive a kidney
from an adult donor. In this situation, it is possible
for a large amount of blood (150250 ml) to be
sequestered into the organ upon vascular unclamping. This may be a significant portion of the pediatric
recipients blood volume and may result in hypovolemia and hypotension upon reperfusion. Central
venous pressure monitoring is helpful in anticipation of this problem and also because urine output is
an unreliable indicator of volume status in these
patients. In some circumstances a unit of packed
RBCs is administered prior to reperfusion of the
donor kidney.

I. Liver transplantation
Pediatric liver transplant patients are often anemic.
Chronic disease, nutritional deficiencies, and occult
blood loss contribute to decreased hemoglobin
levels. These patients are typically coagulopathic
for a variety of reasons including but not limited to
hypersplenism and decreased clotting factor production. Malabsorption of vitamin K leads to
decreased production of vitamin K-dependent factors II, VII, IX and X resulting in elevated PT and
PTT. Thrombocytopenia may be the result of splenic
sequestration secondary to portal hypertension, DIC,
or dilution from increased plasma volume. Although
preoperative coagulation tests have not been shown
to correlate with intraoperative blood loss during
pediatric liver transplantation, they are important
indicators of the severity of liver disease and help to
establish a baseline to which intraoperative values
can be compared (133, 134). Hemoglobin levels,
platelet numbers, PT and PTT values and whole
blood clotting assays such as the thromboelastogram
(TEG) are used to guide perioperative blood product
administration.
Pediatric liver transplant patients are at even
higher risk than adults for requiring massive transfusion. Infants have demonstrated increased trans-

fusion needs during liver transplant than older

children and adults (135). Previous abdominal surgery has been linked to increased blood use during
liver transplantation (134). The most common etiology of pediatric liver failure is biliary atresia for
which previous abdominal surgery (i.e. Kasai portoenterostomy), is often performed prior to transplant. The use of reduced-sized donor livers is
common in children because they often receive a
lobe or segment of a living related donor organ, or a
split cadaver organ which can serve two patients.
The use of reduced sized grafts has also been
associated with increased intraoperative bleeding
(136).
Adequate venous access is critical for these
patients. Large bore intravenous lines should be
placed in the upper extremities because the inferior
vena cava may be cross-clamped intraoperatively. If
adequate access in the upper extremities is not
possible, large bore access may be placed via the
subclavian or jugular veins. Great care must be taken
when inserting large central venous cannulas in the
neck region if coagulopathy exists as hematoma
formation may be difficult to control. Ultrasound
guided catheter insertion may be very advantageous
in this population (137, 138). The hospital blood
bank must have well-organized and well-equipped
resources to handle the potential massive transfusion needs of these patients (multiple blood volumes). Our blood bank defines massive blood
transfusion according to Table 4. For this population, our practice is to have one blood volume of
cross-matched packed RBCs, five to 15 units of fresh
frozen plasma and two to four plasma pheresis
packs of platelets. After one blood volume of blood
Table 4
Units of crossed matched blood transfused within 24 h after
which cross-match is no longer required and type specific red
blood cells may be utilized
Patient weight (kg)
0.57
715
1620
2125
2630
3135
3640
4150
>50

Packed red blood cell units transfused per 24 h

2
3
4
5
6
7
8
9
10

2005 Blackwell Publishing Ltd, Pediatric Anesthesia, 15, 814830

INTRAOPERATIVE BLOOD TRANSFUSION THERAPY

transfusion a cross-match is not required and type

specific packed RBCs are used. The anesthesiologist
must be prepared for complications of massive
blood transfusion including hypothermia, hypocalcemia, hypomagnesemia, and hyperkalemia. Citrate
induced hypocalcemia is a particular problem in
these patients because of decreased ability to metabolize citrate secondary to liver failure and the
inability to metabolize citrate during the anhepatic
stage of the transplantation. If rapid and massive
transfusion is expected, a calcium chloride infusion
may be prudent to avoid hemodynamic instability
caused by rapidly changing ionized calcium levels.

V: Reduction of allogeneic blood

administration
There are multiple methods aimed at reducing
perioperative homologous blood administration
(139, 140). For planned surgery in which blood
transfusion is expected (e.g. scoliosis repair), the
possibilities of autologous blood donation, erythropoietin therapy, and cell salvage should be considered. Autologous blood donation involves the
removal of the patients blood a week or more prior
to surgery. This blood is then treated and processed
by a blood bank center and is released for that
specific patients use on the day of surgery. This
process theoretically limits the likelihood of transfusion related infectious disease (except bacterial)
and decreases the incidence of incompatibility
issues. The unit must be cross-matched to a fresh
sample of the patients blood prior to release.
However, clerical error in processing, labeling,
testing, and final checking of the unit is still possible,
and thus administration of what is deemed an
autologous unit is not without risk. In addition, the
metabolic consequences of transfusion of autologous
blood are the same as with allogeneic transfusion.
Autologous blood is often stored as whole blood and
will thus contain all clotting factors in normal
concentrations except labile factors V and VIII.
Whole blood will also carry an increased risk for
hyperkalemia and/or hypocalcemia if older than
7 days and rapidly administered. The hematocrit
will be lower than packed RBCs. Autologous donation has successfully decreased allogeneic blood
transfusion for children 825 kg undergoing orthopedic or abdominal procedures (141).

2005 Blackwell Publishing Ltd, Pediatric Anesthesia, 15, 814830

825

An alternative method of autologous blood use

without predonation through a blood bank is acute
normovolemic hemodilution (ANH) at the beginning of surgery and prior to the onset of surgical
blood loss. With this method, blood is removed
from the patient (usually from an arterial line) and
collected into appropriate storage bags (placed on a
scale to quantitate the volume removed). Careful
replacement of the removed blood volume with
crystalloid in a 3 : 1 ratio is important in order to
maintain normovolemia. The amount of blood to be
removed should be precalculated and the collection
bag weighed in order to avoid withdrawal of too
much blood. This is important when caring for
small children because one must think in the terms
of milliliters of blood instead of units of blood. The
anesthesiologist must also be careful not to overfill
the storage bag. The storage bags contain a specified amount of citrate as an anticoagulant for
450 ml of whole blood. If the bag is overfilled,
there may be insufficient anticoagulant to prevent
thrombus formation. After removal of this blood,
the patient then sheds intraoperative blood with a
lower hematocrit (i.e. fewer RBCs per plasma
volume lost to surgery) and the autologous blood
can be administered after the majority of blood loss
has been completed. The use of ANH has been
shown to effectively decrease the need for allogeneic blood transfusion in adolescent spine surgery
(142). If the removed autologous unit remains in
the operating room (preferably in a cooler to reduce
RBC metabolism and the potential for bacterial
growth), the likelihood of clerical error and incompatibility is minimized, however the metabolic
consequences of transfusion still exist.
Preoperative administration of erythropoietin has
been used to increase hemoglobin levels and reduce
the need for intraoperative or postoperative transfusion (143). Many studies demonstrating the efficacy of erythropoietin have involved adults
undergoing orthopedic procedures (144146). Erythropoietin may also be used in combination with
autologous blood donation to further reduce the
need for allogeneic blood exposure. One small study
involving children undergoing open heart procedures was successful in eliminating allogeneic blood
exposure through a combination of autologous
predonation and erythropoietin therapy over a
period of 2 weeks (147).

8 26

S.L. BARCELONA ET AL.

Intraoperative cell salvage allows surgical blood

loss to be collected, washed, and hemoconcentrated
in preparation for autologous donation. The qualities of cell salvaged blood include an average
hematocrit of 50%, normal erythrocyte survival,
and minimal functional platelets (148). Contraindications for the use of this technique include
surgical field contamination with bacteria, amnionic
fluid, fat, or other potential clotting agents such as
topical thrombin (149). Originally, cancer was a
contraindication to intraoperative blood salvage for
fear of bloodborne tumor spread however an
analysis of six studies in which cell salvage was
used for cancer patients revealed no metastatic
spread (150). Also, the use of a leucocyte filter
further reduces this risk (150). There are no firm
guidelines in the literature for minimal expected
blood loss in order for cell salvage to be considered
cost effective. In our institution, we consider cell
salvage for liver transplant or scoliosis correction
patients over 30 kg.

Conclusions
Surgeons are now much more meticulous in maintaining hemostasis in part because their patients
demand this and anesthesiologists are much more
circumspect with regard to transfusions thereby
minimizing our patients exposure to blood products. These papers were intended to present a
clinically oriented overview of perioperative blood
transfusion practices. Our purpose was to present
the topic in an easily understood format with a
generous use of tables and figures. We hope that we
provided useful strategies for a logical approach to
transfusion therapy and the associated complications as well as insight into the most recent understanding of the coagulation cascade and innovations
in recombinant clotting factor replacement. From
our viewpoint the most important issue is that the
blood pool is becoming increasingly safe through
better screening. The future is even more exciting
with the development of artificial blood, additional
recombinant clotting factors, and new medications
that further improve coagulation thereby further
reducing exposure to allogenic blood products. Our
hope is that blood banks and health care systems
around the world will have the resources to take
advantage of these wonderful innovations.

References
1 Cote CJ, Liu LM, Szyfelbein SK et al. Changes in serial platelet
counts following massive blood transfusion in pediatric
patients. Anesthesiology 1985; 62: 197201.
2 Cote CJ. Blood, colloid, and crystalloid therapy. Anesth Clin
North Am 1991; 9: 865884.
3 Barcelona SL, Cote CJ. Pediatric resuscitation in the operating
room. Anesthesiol Clin North Am 2001; 19: 339365.
4 Miller RD. Complications of massive blood transfusions.
Anesthesiology 1973; 39: 8293.
5 Butenas S, Brummel KE, Bouchard BA et al. How factor VIIa
works in hemophilia. J Thromb Haemost 2003; 1: 11581160.
6 Schlesinger KW, Ragni MV. Safety of the new generation
recombinant factor concentrates. Expert Opin Drug Saf 2002; 1:
213223.
7 Shapiro AD. Recombinant factor VIIa in the treatment of
bleeding in hemophilic children with inhibitors. Semin Thromb
Hemost 2000; 26: 413419.
8 Seremetis S. Dose optimization of recombinant factor VIIa in
the treatment of acute bleeding in haemophilia-associated
inhibitors. Blood Coagul Fibrinolysis 2003; 14 Suppl 1: S29S30.
9 Dejgaard A. Update on Novo Nordisks clinical trial programme on NovoSeven. Blood Coagul Fibrinolysis 2003; 14
Suppl. 1: S39S41.
10 Girard TJ, Nicholson NS. The role of tissue factor/factor VIIa
in the pathophysiology of acute thrombotic formation. Curr
Opin Pharmacol 2001; 1: 159163.
11 Midathada MV, Mehta P, Waner M et al. Recombinant factor
VIIa in the treatment of bleeding. Am J Clin Pathol 2004; 121:
124137.
12 Gerotziafas GT, Chakroun T, Depasse F et al. The role of
platelets and recombinant factor VIIa on thrombin generation,
platelet activation and clot formation. Thromb Haemost 2004;
91: 977985.
13 Goodnough LT, Shander A, Brecher ME. Transfusion medicine: looking to the future. Lancet 2003; 361: 161169.
14 Drews RE. Critical issues in hematology: anemia, thrombocytopenia, coagulopathy, and blood product transfusions in
critically ill patients. Clin Chest Med 2003; 24: 607622.
15 Laurian Y. Treatment of bleeding in patients with platelet
disorders: is there a place for recombinant factor VIIa? Pathophysiol Haemost Thromb 2002; 32 Suppl. 1: 3740.
16 Lynn M, Jeroukhimov I, Klein Y et al. Updates in the management of severe coagulopathy in trauma patients. Intensive
Care Med 2002; 28 Suppl 2: S241S247.
17 Jurlander B, Thim L, Klausen NK et al. Recombinant activated
factor VII (rFVIIa): characterization, manufacturing, and
clinical development. Semin Thromb Hemost 2001; 27: 373384.
18 Poon MC. Management of thrombocytopenic bleeding: is
there a role for recombinant coagulation factor VIIa? Curr
Hematol Rep 2003; 2: 139147.
19 Kjalke M, Ezban M, Monroe DM et al. High-dose factor
VIIa increases initial thrombin generation and mediates
faster platelet activation in thrombocytopenia-like conditions in a cell-based model system. Br J Haematol 2001; 114:
114120.
20 Hedner U, Ingerslev J. Clinical use of recombinant FVIIa
(rFVIIa). Transfus Sci 1998; 19: 163176.
21 Erhardtsen E. Pharmacokinetics of recombinant activated
factor VII (rFVIIa). Semin Thromb Hemost 2000; 26: 385391.
22 Abshire TC. Dose optimization of recombinant factor VIIa for
control of mild to moderate bleeds in inhibitor patients:

2005 Blackwell Publishing Ltd, Pediatric Anesthesia, 15, 814830

INTRAOPERATIVE BLOOD TRANSFUSION THERAPY

23

24

25

26

27

28

29

30

31

32

33

34

35

36

37

38

39

Improved efficacy with higher dosing. Semin Hematol 2004; 41

Suppl. 1: 37.
Martinowitz U, Kenet G, Lubetski A et al. Possible role of
recombinant activated factor VII (rFVIIa) in the control of
hemorrhage associated with massive trauma. Can J Anaesth
2002; 49: S15S20.
Al Douri M, Shafi T, Al Khudairi D et al. Effect of the
administration of recombinant activated factor VII (rFVIIa;
NovoSeven) in the management of severe uncontrolled
bleeding in patients undergoing heart valve replacement
surgery. Blood Coagul Fibrinolysis 2000; 11 Suppl. 1: S121S127.
White B, McHale J, Ravi N et al. Successful use of recombinant
FVIIa (Novoseven) in the management of intractable postsurgical intra-abdominal haemorrhage. Br J Haematol 1999;
107: 677678.
ONeill PA, Bluth M, Gloster ES et al. Successful use of
recombinant activated factor VII for trauma-associated hemorrhage in a patient without preexisting coagulopathy.
J Trauma 2002; 52: 400405.
Markiewicz M, Kalicinski P, Kaminski A et al. Acute coagulopathy after reperfusion of the liver graft in children correction with recombinant activated factor VII. Transplant Proc
2003; 35: 23182319.
Naik VN, Mazer CD, Latter DA et al. Successful treatment
using recombinant factor VIIa for severe bleeding post cardiopulmonary bypass. Can J Anaesth 2003; 50: 599602.
Dutton RP, Hess JR, Scalea TM. Recombinant factor VIIa for
control of hemorrhage: early experience in critically ill trauma
patients. J Clin Anesth 2003; 15: 184188.
Eikelboom JW, Bird R, Blythe D et al. Recombinant activated
factor VII for the treatment of life-threatening haemorrhage.
Blood Coagul Fibrinolysis 2003; 14: 713717.
Aldouri M. The use of recombinant factor VIIa in controlling
surgical bleeding in non-haemophiliac patients. Pathophysiol
Haemost Thromb 2002; 32 Suppl. 1: 4146.
Meijer K, Hendriks HG, de Wolf JT et al. Recombinant factor
VIIa in orthotopic liver transplantation: influence on parameters of coagulation and fibrinolysis. Blood Coagul Fibrinolysis 2003; 14: 169174.
Morenski JD, Tobias JD, Jimenez DF. Recombinant activated
factor VII for cerebral injury-induced coagulopathy in pediatric patients. Report of three cases and review of the literature. J Neurosurg 2003; 98: 611616.
Martinowitz U, Kenet G, Segal E et al. Recombinant activated
factor VII for adjunctive hemorrhage control in trauma.
J Trauma 2001; 51: 431438.
Martinowitz U, Holcomb JB, Pusateri AE et al. Intravenous
rFVIIa administered for hemorrhage control in hypothermic
coagulopathic swine with grade V liver injuries. J Trauma
2001; 50: 721729.
Surudo T, Wojcicki M, Milkiewicz P et al. Rapid correction of
prothrombin time after low-dose recombinant factor VIIA in
patients undergoing orthotopic liver transplantation. Transplant Proc 2003; 35: 23232325.
Gabriel DA, Carr M, Roberts HR. Monitoring coagulation and
the clinical effects of recombinant factor VIIa. Semin Hematol
2004; 41 Suppl. 1: 2024.
Rajwal S, Richards M, OMeara M. The use of recalcified
citrated whole blood a pragmatic approach for thromboelastography in children. Paediatr Anaesth 2004; 14: 656660.
Srinivasa V, Gilbertson LI, Bhavani-Shankar K. Thromboelastography: where is it and where is it heading? Int Anesthesiol Clin 2001; 39: 3549.

2005 Blackwell Publishing Ltd, Pediatric Anesthesia, 15, 814830

827

40 Whitten CW, Greilich PE. Thromboelastography: past, present, and future. Anesthesiology 2000; 92: 12231225.
41 Dunkley SM, Mackie F. Recombinant factor VIIa used to control
massive haemorrhage during renal transplantation surgery;
vascular graft remained patent. Hematology 2003; 8: 263264.
42 Tobias JD, Berkenbosch JW, Muruve NA et al. Correction of a
coagulopathy using recombinant factor VII before removal of
an intra-aortic balloon pump. J Cardiothorac Vasc Anesth 2002;
16: 612614.
43 Tobias JD, Berkenbosch JW, Russo P. Recombinant factor VIIa
to treat bleeding after cardiac surgery in an infant. Pediatr Crit
Care Med 2003; 4: 4951.
44 Pychynska-Pokorska M, Moll JJ, Krajewski W et al. The use of
recombinant coagulation factor VIIa in uncontrolled postoperative bleeding in children undergoing cardiac surgery with
cardiopulmonary bypass. Pediatr Crit Care Med 2004; 5: 246
250.
45 Egan JR, Lammi A, Schell DN et al. Recombinant activated
factor VII in paediatric cardiac surgery. Intensive Care Med
2003; 30: 682685.
46 Brown JB, Emerick KM, Brown DL et al. Recombinant factor
VIIa improves coagulopathy caused by liver failure. J Pediatr
Gastroenterol Nutr 2003; 37: 268272.
47 Chuansumrit A, Visanuyothin N, Puapunwattana S et al.
Outcome of intracranial hemorrhage in infants with congenital factor VII deficiency. J Med Assoc Thai 2002; 85 Suppl. 4:
S1059S1064.
48 Chuansumrit A, Chantarojanasiri T, Isarangkura P et al.
Recombinant activated factor VII in children with acute
bleeding resulting from liver failure and disseminated intravascular coagulation. Blood Coagul Fibrinolysis 2000; 11 Suppl.
1: S101S105.
49 Almeida AM, Khair K, Hann I et al. The use of recombinant
factor VIIa in children with inherited platelet function disorders. Br J Haematol 2003; 121: 477481.
50 Veldman A, Fischer D, Voigt B et al. Life-threatening hemorrhage in neonates: management with recombinant activated
factor VII. Intensive Care Med 2002; 28: 16351637.
51 Greisen G, Andreasen RB. Recombinant factor VIIa in preterm
neonates with prolonged prothrombin time. Blood Coagul Fibrinolysis 2003; 14: 117120.
52 Sauaia A, Moore FA, Moore EE et al. Epidemiology of trauma
deaths: a reassessment. J Trauma 1995; 38: 185193.
53 Pinsky MR. Probing the limits of arterial pulse contour analysis to predict preload responsiveness. Anesth Analg 2003; 96:
12451247.
54 Idris A, Melker RJ. High-flow sheaths for pediatric fluid
resuscitation: a comparison of flow rates with standard
pediatric catheters. Pediatr Emerg Care 1992; 8: 119122.
55 Goldstein B, Doody D, Briggs S. Emergency intraosseous
infusion in severely burned children. Pediatr Emerg Care 1990;
6: 195197.
56 Tighe SQ, Rudland SV, Kemp PM et al. Paediatric resuscitation in adverse circumstances: a comparison of three routes of
systemic access. J R Nav Med Serv 1993; 79: 7579.
57 Velasco AL, Delgado-Paredes C, Templeton J et al. Intraosseous infusion of fluids in the initial management of hypovolemic shock in young subjects. J Pediatr Surg 1991; 26: 48.
58 Wade CE, Grady JJ, Kramer GC. Efficacy of hypertonic saline
dextran fluid resuscitation for patients with hypotension from
penetrating trauma. J Trauma 2003; 54 Suppl. 5: S144S148.
59 Wade CE, Grady JJ, Kramer GC et al. Individual patient
cohort analysis of the efficacy of hypertonic saline/dextran in

8 28

60

61

62

63

64
65

66

67

68
69

70

71
72

73

74

75
76

77

78

79

80

S.L. BARCELONA ET AL.

patients with traumatic brain injury and hypotension.

J Trauma 1997; 42 Suppl. 5: S61S65.
Maningas PA, Mattox KL, Pepe PE et al. Hypertonic salinedextran solutions for the prehospital management of traumatic hypotension. Am J Surg 1989; 157: 528533.
Stump DC, Strauss RG, Henriksen RA et al. Effects of
hydroxyethyl starch on blood coagulation, particularly factor
VIII. Transfusion 1985; 25: 349354.
Strauss RG, Stump DC, Henriksen RA et al. Effects of
hydroxyethyl starch on fibrinogen, fibrin clot formation, and
fibrinolysis. Transfusion 1985; 25: 230234.
Patt A, McCroskey BL, Moore EE. Hypothermia-induced
coagulopathies in trauma. Surg Clin North Am 1988; 68: 775
785.
Counts RB, Haisch C, Simon TL et al. Hemostasis in massively
transfused trauma patients. Ann Surg 1979; 190: 9199.
Murray DJ, Olson J, Strauss R et al. Coagulation changes
during packed red cell replacement of major blood loss.
Anesthesiology 1988; 69: 839845.
Cote CJ. Changes in prothrombin and partial thromboplastin
times during massive blood loss in children undergoing
Harrington rod instrumentation. Section on Anesthesiology.
American Academy of Pediatrics, 1988.
Murray DJ, Pennell BJ, Weinstein SL et al. Packed red cells in
acute blood loss: dilutional coagulopathy as a cause of
surgical bleeding. Anesth Analg 1995; 80: 336342.
Cohen A, Manno C. Transfusion practices in infants receiving
assisted ventilation. Clin Perinatol 1998; 25: 97111.
Warren LJ, Simmer K, Roxby D et al. DNA polymorphism
analysis in transfusion-associated graft-versus-host disease.
J Paediatr Child Health 1999; 35: 98101.
Floss AM, Strauss RG, Goeken N et al. Multiple transfusions
fail to provoke antibodies against blood cell antigens in
human infants. Transfusion 1986; 26: 419422.
Manno CS. Whats new in transfusion medicine? Pediatr Clin
North Am 1996; 43: 793808.
DePalma L, Yu M, McIntosh CL et al. Changes in lymphocyte
subpopulations as a result of cardiopulmonary bypass. The
effect of blood transfusion. J Thorac Cardiovasc Surg 1991; 101:
240244.
Colon-Otero G, Gilchrist GS, Holcomb GR et al. Preoperative
evaluation of hemostasis in patients with congenital heart
disease. Mayo Clin Proc 1987; 62: 379385.
Gill JC, Wilson AD, Endres-Brooks J et al. Loss of the largest
von Willebrand factor multimers from the plasma of patients
with congenital cardiac defects. Blood 1986; 67: 758761.
Chambers LA, Cohen DM, Davis JT. Transfusion patterns in
pediatric open heart surgery. Transfusion 1996; 36: 150154.
Petaja J, Lundstrom U, Leijala M et al. Bleeding and use of
blood products after heart operations in infants. J Thorac
Cardiovasc Surg 1995; 109: 524529.
Kern FH, Morana NJ, Sears JJ et al. Coagulation defects in
neonates during cardiopulmonary bypass. Ann Thorac Surg
1992; 54: 541546.
Miller BE, Mochizuki T, Levy JH et al. Predicting and treating
coagulopathies after cardiopulmonary bypass in children.
Anesth Analg 1997; 85: 11961202.
Williams GD, Bratton SL, Ramamoorthy C. Factors associated
with blood loss and blood product transfusions: a multivariate analysis in children after open-heart surgery. Anesth Analg
1999; 89: 5764.
von Segesser LK, Tozzi P, Mallbiabrrena I et al. Miniaturization in cardiopulmonary bypass. Perfusion 2003; 18: 219224.

81 Friesen RH, Campbell DN, Clarke DR et al. Modified ultrafiltration attenuates dilutional coagulopathy in pediatric open
heart operations. Ann Thorac Surg 1997; 64: 17871789.
82 Friesen RH, Tornabene MA, Coleman SP. Blood conservation
during pediatric cardiac surgery: ultrafiltration of the extracorporeal circuit volume after cardiopulmonary bypass.
Anesth Analg 1993; 77: 702707.
83 Stein JI, Gombotz H, Rigler B et al. Open heart surgery in
children of Jehovahs Witnesses: extreme hemodilution on
cardiopulmonary bypass. Pediatr Cardiol 1991; 12: 170174.
84 Mossad E, Estafanous F. Blood use in cardiac surgery and the
limitations of hemodilution. Curr Opin Cardiol 1995; 10: 584
590.
85 Fukumura F, Sese A, Ueno Y et al. Haemostatic profile of
small children during and following cardiopulmonary
bypass. Jpn J Thorac Cardiovasc Surg 2003; 51: 577581.
86 Nakamura Y, Masuda M, Toshima Y et al. Comparative study
of cell saver and ultrafiltration nontransfusion in cardiac
surgery. Ann Thorac Surg 1990; 49: 973978.
87 Dittrich S, Aktuerk D, Seitz S et al. Effects of ultrafiltration
and peritoneal dialysis on proinflammatory cytokines during
cardiopulmonary bypass surgery in newborns and infants.
Eur J Cardiothorac Surg 2004; 25: 935940.
88 Ootaki Y, Yamaguchi M, Yoshimura N et al. Efficacy of a
criterion-driven transfusion protocol in patients having
pediatric cardiac surgery. J Thorac Cardiovasc Surg 2004; 127:
953958.
89 Mossinger H, Dietrich W, Braun SL et al. High-dose aprotinin
reduces activation of hemostasis, allogeneic blood requirement, and duration of postoperative ventilation in pediatric
cardiac surgery. Ann Thorac Surg 2003; 75: 430437.
90 Pouard P. Review of efficacy parameters. Ann Thorac Surg
1998; 65 Suppl. 6: S40S43.
91 Huang H, Ding W, Su Z et al. Mechanism of the preserving
effect of aprotinin on platelet function and its use in cardiac
surgery. J Thorac Cardiovasc Surg 1993; 106: 1118.
92 Coniff RF. The Bayer 022 compassionate-use pediatric study.
Ann Thorac Surg 1998; 65 Suppl. 6: S31S33.
93 Boldt J, Knothe C, Zickmann B et al. Comparison of two
aprotinin dosage regimens in pediatric patients having
cardiac operations. Influence on platelet function and blood
loss. J Thorac Cardiovasc Surg 1993; 105: 705711.
94 Ranucci M, Corno A, Pavesi M et al. Renal effects of low dose
aprotinin in pediatric cardiac surgery. Minerva Anestesiol 1994;
60: 361366.
95 Dobkowski WB, Murkin JM. A risk-benefit assessment of
aprotinin in cardiac surgical procedures. Drug Saf 1998; 18:
2141.
96 Cohen DM, Norberto J, Cartabuke R et al. Severe anaphylactic
reaction after primary exposure to aprotinin. Ann Thorac Surg
1999; 67: 837838.
97 Carrel TP, Schwanda M, Vogt PR et al. Aprotinin in pediatric
cardiac operations: a benefit in complex malformations and with
high-dose regimen only. Ann Thorac Surg 1998; 66: 153158.
98 DErrico CC. Pharmacoeconomics analysis in a pediatric
population. Ann Thorac Surg 1998; 65 Suppl. 6: S52S54.
99 Mossinger H, Dietrich W. Activation of hemostasis during
cardiopulmonary bypass and pediatric aprotinin dosage. Ann
Thorac Surg 1998; 65 Suppl. 6: S45S50.
100 Dietrich W. Incidence of hypersensitivity reactions. Ann
Thorac Surg 1998; 65 Suppl. 6: S60S64.
101 Dietrich W, Spath P, Ebell A et al. Prevalence of anaphylactic
reactions to aprotinin: analysis of two hundred forty-eight

2005 Blackwell Publishing Ltd, Pediatric Anesthesia, 15, 814830

INTRAOPERATIVE BLOOD TRANSFUSION THERAPY

102

103

104

105

106

107

108
109

110

111

112

113

114

115

116

117

118

119

120

reexposures to aprotinin in heart operations. J Thorac Cardiovasc Surg 1997; 113: 194201.
Handler SD, Miller L, Richmond KH et al. Post-tonsillectomy
hemorrhage: incidence, prevention and management.
Laryngoscope 1986; 96: 12431247.
Crysdale WS, Russel D. Complications of tonsillectomy and
adenoidectomy in 9409 children observed overnight. CMAJ
1986; 135: 11391142.
Wei JL, Beatty CW, Gustafson RO. Evaluation of posttonsillectomy hemorrhage and risk factors. Otolaryngol Head Neck
Surg 2000; 123: 229235.
Postma DS, Folsom F. The case for an outpatient approach
for all pediatric tonsillectomies and/or adenoidectomies: a
4-year review of 1419 cases at a community hospital. Otolaryngol Head Neck Surg 2002; 127: 101108.
Asaf T, Reuveni H, Yermiahu T et al. The need for routine
pre-operative coagulation screening tests (prothrombin time
PT/partial thromboplastin time PTT) for healthy children
undergoing elective tonsillectomy and/or adenoidectomy. Int
J Pediatr Otorhinolaryngol 2001; 61: 217222.
Zwack GC, Derkay CS. The utility of preoperative hemostatic
assessment in adenotonsillectomy. Int J Pediatr Otorhinolaryngol 1997; 39: 6776.
Krishna P, Lee D. Post-tonsillectomy bleeding: a meta-analysis. Laryngoscope 2001; 111: 13581361.
Close HL, Kryzer TC, Nowlin JH et al. Hemostatic assessment
of patients before tonsillectomy: a prospective study. Otolaryngol Head Neck Surg 1994; 111: 733738.
Lippi G, Manzato F, Franchini M et al. Establishment of
reference values for the PFA-100 platelet function analyzer in
pediatrics. Clin Exp Med 2001; 1: 6970.
Fressinaud E, Veyradier A, Truchaud F et al. Screening for
von Willebrand disease with a new analyzer using high shear
stress: a study of 60 cases. Blood 1998; 91: 13251331.
Derkay CS, Werner E, Plotnick E. Management of children
with von Willebrand disease undergoing adenotonsillectomy.
Am J Otolaryngol 1996; 17: 172177.
Judkins JH, Dray TG, Hubbell RN. Intraoperative ketorolac
and posttonsillectomy bleeding. Arch Otolaryngol Head Neck
Surg 1996; 122: 937940.
Splinter WM, Rhine EJ, Roberts DW et al. Preoperative
ketorolac increases bleeding after tonsillectomy in children.
Can J Anaesth 1996; 43: 560563.
Gunter JB, Varughese AM, Harrington JF et al. Recovery and
complications after tonsillectomy in children: a comparison of
ketorolac and morphine. Anesth Analg 1995; 81: 11361141.
Gallagher JE, Blauth J, Fornadley JA. Perioperative ketorolac
tromethamine and postoperative hemorrhage in cases of tonsillectomy and adenoidectomy. Laryngoscope 1995; 105: 606
609.
Rusy LM, Houck CS, Sullivan LJ et al. A double-blind evaluation of ketorolac tromethamine versus acetaminophen in
pediatric tonsillectomy: analgesia and bleeding. Anesth Analg
1995; 80: 226229.
Romsing J, Ostergaard D, Walther-Larsen S et al. Analgesic
efficacy and safety of preoperative versus postoperative ketorolac in paediatric tonsillectomy. Acta Anaesthesiol Scand
1998; 42: 770775.
Agrawal A, Gerson CR, Seligman I et al. Postoperative hemorrhage after tonsillectomy: use of ketorolac tromethamine.
Otolaryngol Head Neck Surg 1999; 120: 335339.
Kovesi T, Royston D. Pharmacological approaches to reducing allogeneic blood exposure. Vox Sang 2003; 84: 210.

2005 Blackwell Publishing Ltd, Pediatric Anesthesia, 15, 814830

829

121 Goobie SM, Soriano SG, Zurakowski D et al. Hemostatic

changes in pediatric neurosurgical patients as evaluated by
thrombelastograph. Anesth Analg 2001; 93: 887892.
122 Curreri PW, Hicks JE, Aronoff RJ et al. Inhibition of active
sodium transport in erythrocytes from burned patients. Surg
Gynecol Obstet 1974; 139: 538540.
123 Simon TL, Curreri PW, Harker LA. Kinetic characterization of
hemostasis in thermal injury. J Lab Clin Med 1977; 89: 702711.
124 Cullen JJ, Murray DJ, Kealey GP. Changes in coagulation
factors in patients with burns during acute blood loss. J Burn
Care Rehabil 1989; 10: 517522.
125 Sheridan RL, Szyfelbein SK. Trends in blood conservation in
burn care. Burns 2001; 27: 272276.
126 Ikeda S, Schweiss JF. Maximum infusion rates and CVP
accuracy during high-flow delivery through multilumen
catheters. Crit Care Med 1985; 13: 586588.
127 Nissenson AR, Strobos J. Iron deficiency in patients with renal
failure. Kidney Int Suppl 1999; 69: S18S21.
128 Montini G, Zacchello G, Baraldi E et al. Benefits and risks of
anemia correction with recombinant human erythropoietin in
children maintained by hemodialysis. J Pediatr 1990; 117: 556
560.
129 Chavers BM, Sullivan EK, Tejani A et al. Pre-transplant blood
transfusion and renal allograft outcome: a report of the North
American Pediatric Renal Transplant Cooperative Study.
Pediatr Transplant 1997; 1: 2228.
130 Butt ML, Shafi T, Farooqi I et al. Effect of dialysis on bleeding
time in chronic renal failure. J Pak Med Assoc 1998; 48: 242244.
131 Remuzzi G, Livio M, Marchiaro G et al. Bleeding in renal
failure: altered platelet function in chronic uraemia only partially corrected by haemodialysis. Nephron 1978; 22: 347353.
132 Mannucci PM, Remuzzi G, Pusineri F et al. Deamino-8-Darginine vasopressin shortens the bleeding time in uremia.
N Engl J Med 1983; 308: 812.
133 Bontempo FA, Lewis JH, Van Thiel DH et al. The relation of
preoperative coagulation findings to diagnosis, blood usage,
and survival in adult liver transplantation. Transplantation
1985; 39: 532536.
134 Carlier M, Van Obbergh LJ, Veyckemans F et al. Hemostasis
in children undergoing liver transplantation. Semin Thromb
Hemost 1993; 19: 218222.
135 Eckhoff DE, DAlessandro AM, Knechtle SJ et al. 100 consecutive liver transplants in infants and children: an 8-year
experience. J Pediatr Surg 1994; 29: 11351139.
136 Kalayoglu M, DAlessandro AM, Sollinger HW et al. Experience with reduced-size liver transplantation. Surg Gynecol
Obstet 1990; 171: 139147.
137 Basford TJ, Poenaru D, Silva M. Comparison of delayed
complications of central venous catheters placed surgically or
radiologically in pediatric oncology patients. J Pediatr Surg
2003; 38: 788792.
138 Randolph AG, Cook DJ, Gonzales CA et al. Ultrasound
guidance for placement of central venous catheters: a metaanalysis of the literature. Crit Care Med 1996; 24: 20532058.
139 Goodnough LT, Brecher ME, Kanter MH et al. Transfusion
medicine. First of two partsblood transfusion. N Engl J Med
1999; 340: 438447.
140 Goodnough LT, Brecher ME, Kanter MH et al. Transfusion
medicine. Second of two parts blood conservation. N Engl
J Med 1999; 340: 525533.
141 Mayer MN, de Montalembert M, Audat F et al. Autologous
blood donation for elective surgery in children weighing 8
25 kg. Vox Sang 1996; 70: 224228.

8 30

S.L. BARCELONA ET AL.

142 Copley LA, Richards BS, Safavi FZ et al. Hemodilution

as a method to reduce transfusion requirements in
adolescent spine fusion surgery. Spine 1999; 24: 219
222.
143 Goodnough LT. Erythropoietin therapy versus red cell
transfusion. Curr Opin Hematol 2001; 8: 405410.
144 Rosencher N, Ozier Y. [Peri-operative use of EPO]. Transfus
Clin Biol 2003; 10: 159164.
145 Tamir L, Fradin Z, Fridlander M et al. Recombinant human
erythropoietin reduces allogeneic blood transfusion requirements in patients undergoing major orthopedic surgery.
Haematologia (Budap) 2000; 30: 193201.
146 Feagan BG, Wong CJ, Kirkley A et al. Erythropoietin with iron
supplementation to prevent allogeneic blood transfusion in
total hip joint arthroplasty. A randomized, controlled trial.
Ann Intern Med 2000; 133: 845854.

147 Horiba K, Itou Y, Terada H et al. Experience of predeposit

autologous blood transfusion and medication of recombinant
human erythropoietin in pediatric open heart surgery. Kyobu
Geka 1991; 44: 11461150.
148 Ley SJ. Intraoperative and postoperative blood salvage.
AACN Clin Issues 1996; 7: 238248.
149 Napier JA, Bruce M, Chapman J et al. Guidelines for autologous transfusion. II. Perioperative haemodilution and cell
salvage. British Committee for Standards in Haematology
Blood Transfusion Task Force. Autologous Transfusion
Working Party. Br J Anaesth 1997; 78: 768771.
150 Elias D, Lapierre V, Billard V. Perioperative autotransfusion
with salvage blood in cancer surgery. Ann Fr Anesth Reanim
2000; 19: 739744.

Accepted 13 September 2004

2005 Blackwell Publishing Ltd, Pediatric Anesthesia, 15, 814830