1. Transfusion and Apheresis Science 45 (2011) 281–285
Contents lists available at SciVerse ScienceDirect
Transfusion and Apheresis Science
journal homepage: www.elsevier.com/ locate/ transci
Integrated strategies for allogeneic blood saving in major elective surgery
Maria Beatrice Rondinelli a,⇑, Francesco Pallotta b, Sandro Rossetti b, Francesco Musumeci c,
Antonio Menichetti c, Franco Bianco d, Marco Gaffi b, Luca Pierelli a,e
a Department of Transfusion Medicine, San Camillo Forlanini Hospital, Rome, Italy
b Department of General Surgery, San Camillo Forlanini Hospital, Rome, Italy
c Department of Cardiovascular Surgery, San Camillo Forlanini Hospital, Rome, Italy
d Department of Anaesthesiology Surgery, San Camillo Forlanini Hospital, Rome, Italy
e Department of Experimental Medicine, La Sapienza University, Rome, Italy
a r t i c l e i n f o
Keywords:
Autologous blood
Red blood cell storage
Peri-surgical blood transfusions
Blood-saving
a b s t r a c t
Background: Large use of allogeneic red blood cell concentrates (RBCc), albeit necessary in
major surgery, may influence patients’ outcome.
Design and methods: We introduced an integrated strategy including patients’ evaluation
and supplementation associated with autologous blood collection and saving to support
major elective surgery at our hospital since 2008. After 2 years of stabilization of this
approach, we analyzed the results obtained in 2010 in terms of allogeneic blood usage
and reduction of transfusion of stored RBCc.
Results: Analyzing 2010 results we found that usage of total autologous RBCc units was
increased by 2.2 folds, of ‘‘not stored’’ autologous RBCc units by 2.4 folds and of alloge-neic
RBCc unit transfusion reduced by 65%. The significant reduction in the number of
transfused allogeneic RBCc units associated with the use of ‘‘fresher’’ blood could pre-vent
patients’ complications due to immunomodulation and biologic/metabolic
disregulation.
2011 Elsevier Ltd. All rights reserved.
1. Introduction
The current use of red blood cell concentrates (RBCc) in
transfusion support of patients undergoing major surgery
is a standard and effective practice to counteract blood loss
and consequent hemodynamic effects related to acute ane-mia
and hemodilution. Tissue oxygenation requires an
adequate hemoglobin concentration in circulating blood
and a sufficient tissue perfusion is function of heart activity
which is sustained by a proper myocardium oxygenation
by coronary flow and oxygen transportation. Beyond
certain limits acute blood loss reduced oxygen transporta-tion
but not tissue perfusion which increases until a
hemoglobin (Hb) concentration is maintained around the
value of 10 g/dL; when acute blood loss determines an
Hb decrease below 10 to 9 g/dL, tissue oxygenation
decreases without increase in tissue perfusion and in the
absence of potentiating mechanisms for oxygen tissue
delivery due to the lack of so prompt metabolic changes
translating into Hb affinity reduction at tissue levels
[1–3]. Hence, the reaching of Hb values below 7 to 6 g/dL
in an acute fashion determines a progressive failure in
aerobic metabolism which results in significant reduction
of energetic compounds and acidosis. At this stage, RBCc
transfusion is the only chance to recover tissue oxygena-tion
and generalized energy failure. Generally, these
circumstances occur when more than 50% of blood volume
is lost in a short time in a subject who has a pre-bleeding
normal Hb values or after 30–40% of blood loss in subjects
who experience hemorrhage with a starting suboptimal
Hb. In these conditions, transfusion of a variable amount
⇑ Corresponding author. Address: Department of Transfusion Medicine,
San Camillo Forlanini Hospital, Circonvallazione Gianicolense n. 87,
00152 Rome, Italy. Tel.: +39 0658703546; fax: +39 0658704258.
E-mail address: mrondinelli@scamilloforlanini.rm.it (M.B. Rondinelli).
1473-0502/$ - see front matter 2011 Elsevier Ltd. All rights reserved.
doi:10.1016/j.transci.2011.10.009

2. of RBCc provides a Hb rise through which tissue oxygena-tion
is gradually recovered. On the other hand, transfusion
of allogeneic blood components influences patient out-come
in a dose-related fashion so that, in several settings
of major surgery, the greater is the number of allogeneic
blood component transfused, the higher is the rate of inter-vention-
related complications such as infections, respira-tory
distress or other organ dysfunction [4–6]. The
reasons of this negative relation between patient transfu-sion
load and outcome is only speculative and likely due
to recipient immunomodulation, inflammatory cytokine
release and clotting/fibrinolysis activation. An attempt to
reduce these detrimental effects may be that of transfusing
pre-storage leukoreduced RBCc with a storage length no
longer than 2 weeks to minimize the negative contribution
of the so called ‘‘ storage lesion’’ on patients’ outcome fol-lowing
transfusion. However, allogeneic blood shortage
occurring for various reasons at certain geographical site,
including seasonal outbreak of new emerging pathogens,
may vanish strategies to reduce the usage of ‘‘older’’ allo-geneic
RBCc [7–9]. In the setting of major surgery, where
the intervention is programmed since several days or
weeks before, an alternative option is that of planning a
program of patient’s preparation to increase his own toler-ance
to blood loss. The key point of this possible option is
that of preliminary patient’s clinical examination (CE) to
plan supplementation treatment (ST), erythropoietin
(EPO) administration, whenever appropriate, followed by
patient’s enrollment in a specific program of autologous
blood collection (i.e., pre-surgical autologous blood dona-tion,
PABD, peri-surgical blood collection, PBC) [10,11].
Hence, integration of patient’s CE, ST (with or without
EPO) with PABD/PBC strategies may contribute to reduce
patient’s exposure to stored allogeneic RBCc, providing a
contribution for donated blood saving and, likely, for
improvement of post-surgical patient’s outcome. Last but
not least, the rate of transfusion transmitted infection for
hepatitis B virus (HBV) is still 1:282,000 in developed
countries of Mediterranean areas and emerging pathogens
due to donor’s travelling or migration is increasing the risk
of transfusion transmitted infections [12–14]. Here we re-port
a single-institution experience in the application of an
integrated strategy of CE/TS/PABD/PBC to support major
elective surgery in a large tertiary care hospital of the city
of Rome.
2. Materials and methods
Since January 2008 at San Camillo Forlanini Hospital (a
tertiary care hospital which includes full programs of
hemato-oncology with stem cell transplantation, heart,
kidney and liver transplantation and a large trauma center,
major abdominal, cardio-vascular and orthopedic surgery)
we have introduced a multi-phase integrated approach for
patient’s evaluation prior to major elective surgery which
includes CE with specific care to hematologic status, in
case, ST, PABD with or without EPO administration, peri-surgical
EPO and a program of PBC, whenever possible
and appropriate. Only patients for whom a request of a
minimum of 2 RBCc units had been made, according to
Table 1
Characteristics of RBCc support for elective major surgery prior to the systematic introduction of the integrated approach for allogeneic blood alternatives (started from January 2008): results observed in the year 2007.
Allogeneic RBCc -median
no. of unitsc
PABDa ANHa PBCa Total autologous RBCcb Total ‘‘non stored’’
Surgical setting EPO
autologous RBCcb
administration
No No 2 (0–2) 0 2 (0–3) 90%
Hip replacement (98 patients) No Yes
(2; 0–2)
No No 1 (0–2) 0 3 (0–3) 80%
Knee replacement (110 patients) No Yes
(1; 0–2)
No No No No 0 0 3 (0–4) 90%
Laparotomic nefrectomy
(77 patients)
2.5 (1–3.5) 2.5 (1–3.5) 2 (0–4) 70%
(61 patients)
No No No Yes IBS
Thoracic aortic surgery
(2.5) range 1–3, 5
Aortic dissection (44 patients) No No No Yes IBS (4.5) range 2–6 4.5 (2–6) 4.5 (2–6) 3 (1–4) 100%
RBCc, red blood cell concentrate; EPO, erythropoietin; PABD, pre-surgical autologous blood donation; PBC, peri-surgical blood collection; ANH, acute normovolemic hemodilution; IBS, intra-surgical blood salvage.
a Median no. of RBCc units.
b Median no. of units.
c % Of patients transfused with allogeneic RBCc.
282 M.B. Rondinelli et al. / Transfusion and Apheresis Science 45 (2011) 281–285

3. M.B. Rondinelli et al. / Transfusion and Apheresis Science 45 (2011) 281–285 283
local maximum surgery blood order schedule (MSBOS),
were enrolled in the present project.
2.1. CE and ST
All patients underwent a CE and subjected to blood
counts, blood chemistry, clotting parameters and iron sta-tus
and, on the basis of mean corpuscular volume (MCV) of
RBC, folate and vitamin B12 serum levels. In the case of a
serum ferritin lower than 15 ng/mL all patients were trea-ted
by daily oral therapy with ferrous sulfate (200 mg/day),
which had been continued until 4 weeks after surgery. In
the case of folic acid deficiency, patients were treated with
oral therapy at the daily dose of 5 mg for 30 days; in pa-tients
with suspected or diagnosed gastrointestinal malab-sorption,
folic acid was given through the intramuscular
route at proper schedule and dosage [15]. Similarly, cyano-cobalamin
was given to patients showing vitamin B12 defi-ciency
through the proper route and at schedule and
dosage depending on the case. All patients treated by ST
were reevaluated after 1 month from treatment start to de-fine
the need for further treatments or additional clinical
and laboratory investigations [16].
2.2. EPO and PABD
All patients not suffering from metastatic cancer, with-out
an active ischemic disease of myocardium or a serious
dysfunction of aortic valve, with a left ventricular ejection
fraction higher than 50%, without cerebral hemorrhage or
thrombosis in the previous 2 years, without history of sei-zures
refractory to pharmacological prophylaxis, without a
HIV infection and with a Hb level higher than 10 g/dL were
evaluated for PABD, with or without EPO administration.
PABD were carried out by collecting 1 unit of 350 mL of
whole blood by a sterile dedicated two-bag collection sys-tem
every 4 days until the 7th day before surgery for a
maximum of 3 units. EPO were administered when pa-tients
had a Hb value comprised between 10 and 13 g/dL
and associated in all cases with daily intake of ferrous sul-fate
at the dose of 200 mg per day. EPO (Epoetin alfa) was
administered subcutaneously at the dose of 80,000 IU per
week until the day of surgery [17,18].
2.3. Peri-surgical use of EPO without PABD
Patients who waited for major elective surgery and
showed suboptimal Hb value (13 and 10 g/dL) and were
not eligible for PABD and who had not a recent history of
thromboembolic disease, received EPO subcutaneously at
the dose 40,000 IU every 3 days since the week prior to
surgery and continued until the first week after surgery,
for a maximum of 4 injections, associated with daily oral
intake of ferrous sulfate (200 mg/day) [18].
2.4. PBC
All patients showing a Hb concentration higher than
13.5 g/dL and prepared for aortic surgery underwent PBC
by acute normovolemic hemodilution (ANH) with collec-tion
of 2 units of at least 350 mL of whole blood each by
a dedicated two-bag collection system which were briefly
stored at room temperature in the surgical area and rein-fused
as soon as possible. Volemic balance was acutely
provided by injection of a volume of crystalloid solution
equal to three times the total blood volume collected.
Patients with documented alteration of clotting factors
other than that related to heparin administration and with
unstable angina or active myocardial ischemia were
excluded from this procedure. Patients not suffering from
neoplastic disease involving the surgical field, without
infections in the surgical area or subjected to surgical
manoeuvres on gastrointestinal, biliary or urinary tracts,
in the absence of irrigating procedures of surgical areas,
underwent PBC by intra-surgical and/or post-surgical
blood salvage (IBS/PBS) by Cardiopath (PBS), Ortopath
(IBS/PBS) Cell Saver (IBS) technologies (Haemonetics,
Braintree, MA,USA technologies) and C.A.T.S. (IBS)
(Fresenius, Bad Hamburg, Germany).
3. Results
The surgical areas where we were able to consistently
introduce the integrated approach for allogeneic blood
alternatives in our Hospital were 4 and included the ortho-pedic
surgery, cardio-vascular surgery, urologic surgery. In
cardiovascular surgery we performed the entire process for
allogeneic blood saving including CE/ST/PABD/PBC even
though the use of PBS was limited to those cases who
needed surgical reintervention. In urologic and orthopedic
surgery we consistently omitted ANH due to the scarce
applicability of this method in this specific setting which
was mainly related to patients’ advanced age and scarce
compliance of the anesthesiology staff with respect to this
technique. In orthopedic surgery interventions for knee
replacement were subjected to a modified PBC approach
which includes sterile blood aspiration during surgery with
a stand-by application of IBS followed by a second-step
aspiration from drainage line for further six hours post-surgery
(PBS) and by blood processing and washing by Ort-hopat
device, whenever a proper blood volume had been
collected. During hip replacement PBC consisted mainly
of IBS in a stand-by approach followed by blood processing
and washing by Orthopat in the case of a minimum of
300 mL of blood has been aspirated. At the starting of the
present project the average use of allogeneic RBCc in the
distinct surgery settings was that shown in Table 1. In de-tail,
surgical interventions for thoracic aortic surgery were
supported with a median of 2 RBCc units, aortic dissection
with 3 units, hip replacement with 3 units, knee replace-ment
with median of 3 and urologic surgery for laparotom-ic
nefrectomy with 3 units. The use of allogeneic RBCc units
was necessary in a proportion of patients ranging from 70%
to 100%, with the minimum for thoracic aortic surgery and
the maximum for aortic dissection. Following 2 years in
which we gradually introduced the integrated strategies
for allogeneic blood saving including CE/TS/PABD/PBC
techniques, we observed, in the course of 2010, a substan-tial
change in the use of allogeneic RBCc units as shown in
Table 2. The number of allogeneic RBCc units had been
reduced by 1 per patient in thoracic aortic surgery, aortic

4. 284 M.B. Rondinelli et al. / Transfusion and Apheresis Science 45 (2011) 281–285
dissection and hip replacement; moreover, we were able to
reduce RBCc units by 2.5 and 3 per patient in laparotomic
nefrectomy and knee replacement, respectively. Apart
from thoracic aortic surgery and aortic dissection where
allogeneic blood was still required in 70% and 100% of
cases, we needed allogeneic RBCc transfusions only in
25% of knee replacements, 55% of hip replacements and
40% of laparotomic nefrectomy. Collectively, in the entire
patients’ cohort total autologous RBCc units were in-creased
by 2.2 folds, ‘‘not stored’’ autologous RBCc units
by 2.4 folds and allogeneic RBCc unit transfusion was
reduced by 65%. An additional considerable result of our
integrated approach is represented by the fact that we
transfused in all cases, except the setting of hip replace-ment,
a proportion of autologous ‘‘not stored’’ RBCc units
ranging from 50% to 80% (50% in laparotomic nefrectomy,
75% in both knee replacement and aortic dissection and
80% in thoracic aortic surgery). In hip replacement we were
unable to transfuse more than 25% of autologous ‘‘not
stored’’ RBCc units due to the prevalent contribution of
PABD strategy as an alternative to allogeneic transfusion
in this specific setting.
4. Discussion
The pursuit of allogeneic blood self-sufficiency, of
reducing the risk of blood transfusion and of emergent
blood-transmittable pathogens is a major goal in modern
transfusion medicine. Reported adverse reactions to allo-geneic
blood, reduction of patients’ survival and with in-crease
in infectious complications in the outcome of
those patients receiving a larger number of allogeneic RBCc
justify the hypothesis of a transfusion dose-related modu-lation
of patients’ defense with disruption of immune, bio-logic
and metabolic equilibrium which is required for
prompt recovery from major surgery and general narcosis
[16]. A realistic and alternative approach to allogeneic
blood transfusion is that of autologous blood collection
preceded by correction of anemic conditions and, when-ever
possible, by expansion of patient’s circulating RBC vol-ume.
In our experience, the introduction of an integrated
approach which includes CE/ST/PABD/PBC produced an
evident change in allogeneic RBCc usage in patients sub-jected
to elective major surgery in the course of 2 years.
Allogeneic blood saving was greater in the setting of knee
replacement where we were able to consistently perform
PBS which produced a considerable autologous blood sav-ing
due to the specific nature of bleeding that, in this kind
of surgery, is higher within 6–8 h from the intervention. On
the contrary, in hip replacement the introduction of IBS
failed to collect more than a median of 1 RBCc unit and this
result could be related to the different timing of bleeding in
this setting which mostly occur after 24 h from interven-tion.
In the setting of thoracic aortic surgery or aortic dis-section
the additional use (in these cases IBS was active
also in 2008) of ANH did not change the proportion of pa-tients
who received allogeneic RBCc units while reduced
the median number of allogeneic units transfused per pa-tient
by 1. In this context, we believe that a further
improvement in allogeneic RBCc saving is unfeasible due
Table 2
Characteristics of RBCc support for elective major surgery after 2 years of the systematic introduction of the integrated approach for allogeneic blood alternatives: results observed in the year 2010.
Allogeneic RBCc -median
no. of unitsc
Total ‘‘non stored’’
autologous RBCcb
Surgical setting EPO administration PABDa ANHa PBCa Total autologous
RBCcb
No Yes IBS (1) range (0–3) 3 (0–4) 1 (0–3) 1 (0–1) 55%
Hip replacement (100 patients) Yes (120,000 IU) Yes
(2; 0–2)
No Yes PBS (3) range (1–3) 4 (1–5) 3 (1–3) 0 (0–1) 25%
Knee replacement (130 patients) Yes (80,000 IU) Yes
(1; 0–2)
No Yes IBS (2) range (1–3) 4 (1–5) 2 (1–3) 0.5 (0–1) 40%
(80 patients)
Yes (120,000 IU) Yes
Laparotomic nefrectomy
(2; 0–2)
Yes IBS (2.5) range (1–3, 5) 4 (1–5) 4 (1–5) 1 (0–2) 70%
(60 patients)
No No Yes (2)
Thoracic aortic surgery
range (0–2)
Yes IBS (4.5) range (2–6) 6 (2–7) 6 (2–7) 2 (1–4) 100%
Aortic dissection (45 patients) No No Yes (2)
range (0–2)
RBCc, red blood cell concentrate; EPO, erythropoietin; PABD, pre-surgical autologous blood donation; PBC, peri-surgical blood collection; ANH, acute normovolemic hemodilution; IBS, intra-surgical blood salvage;
PBS, post-surgical blood salvage.
a Median no. of RBCc units.
b Median no. of units.
c % Of patients transfused with allogeneic RBCc.

5. M.B. Rondinelli et al. / Transfusion and Apheresis Science 45 (2011) 281–285 285
to the specific characteristics of the surgery which requires
a high amount of RBCc to counteract a naturally high intra-operative
blood loss. Another surgical setting which
showed a major result is that of laparotomic nefrectomy
where the use of both PABD and IBS allowed us to reduce
the need of RBCc transfusion of 67%, with the production
and transfusion of 4 autologous RBCc units in 2010, as
compared to none in 2008. Collectively, our approach per-mitted
us to reduce by 65% patients exposure to allogeneic
blood and by 40% to stored RBCc units (autologous + allo-geneic).
As outlined in the introduction of this report, the
increased use of allogeneic RBCc in patients subjected to
surgery relates to a higher number of clinical complica-tions
due to immunomodulation, erythrocyte lesions
occurring during conservation or transfusion-transmitted
infections [17,18]. All of these unfavorable circumstances
may be overcome by a significant reduction in the number
of transfused allogeneic RBCc units. Here, the observed de-crease
in the allogeneic blood and stored RBCc unit usage
in patients with major surgery demonstrated that this re-sult
may be obtained by an integrated approach which in-cludes
CE/ST/PABD/PBC; a further analysis should be
carried out in the near future to investigate whether this
modification in blood usage translates into a better pa-tients’
outcome in a larger cohort of patients [19,20]. Final-ly,
an additional challenge in this setting should be that of
reducing even more the residual transfusional load of
stored RBCc units (autologous + allogeneic) in those pa-tients
who show an Hb level which allows a greater toler-ation
of blood loss during and after surgery.
Funding source
No funding was necessary to complete this article.
Acknowledgements
The authors thank Salvatore Scali, Fabrizio Schirripa,
Stefano Villani, Angela Accarino for performing IBS/PBS
during surgical interventions.
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