Autologous blood transfusion - A review

Abstract

The discovery of HIV and other transfusion-transmissible infections has increased the demand for alternatives to allogeneic blood transfusion. One such alternative is autologous transfusion. This review presents an analysis of autologous transfusion. We conclude that autologous transfusion should form part of a strategy to minimise the risk associated with allogeneic transfusion in Nigeria and other developing countries.

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Allogeneic transfusion is a ubiquitous practice. Once an
unquestioned adjunct to patient care, it is currently being re-
evaluated and alternatives are being considered in response
to concerns about its safety.
1
Some of the complications are immunological, and
are thought to be responsible for the increase in tumour
recurrence after surgical resection,
2,3
increased postoperative
infection rates,
2,4
increased progression of HIV infection,
5
decreased cell mass and occasional transient hypotension,
1
and multiorgan failure.
6
These sequelae can be reduced by
the use of syngeneic or autologous blood, or leucodepleted
allogeneic blood components.
7
Autologous blood transfusion is extremely safe. Cross-
matching is not required; iso-immunisation to foreign protein
is excluded; allogeneic blood is conserved for those who need
it, particularly for emergencies; and the fear of transfusion-
transmissible disease can be ignored.
8
The greatest risk of autologous blood transfusion is clerical
error and bacterial contamination of the autologous unit.
Meticulous attention to standards can eliminate these
problems.
Autologous transfusion is indicated for most elective
operations that do not involve ‘type and screen’. It is
indicated for patients with very rare blood groups or complex
red cell antibodies for whom it is difficult to find compatible
blood, and also for some religious sects (such as Jehovah’s
Witnesses, in whom only intra-operative cell salvage is
permissible).
9
However, this practice is still under-appreciated in Nigeria
and most developing countries. This review aims to provide
information on the nature, clinical outcomes and cost
benefits of autologous blood transfusion.
Forms of autologous blood transfusion
Three main techniques for autologous transfusion are
predeposit autologous donation (PAD), acute normovolaemic
haemodilution (ANH), and perioperative cell salvage (PCS).
Predeposit autologous donation (PAD)
PAD entails repeated preoperative phlebotomy, 4 - 5 weeks
before surgery, during which time 4 or 5 units of in-date
blood can be collected with ease.
1
This technique reduces
exposure to allogeneic blood. It avoids many of the risks
of transfusion, especially immunisation to red cell/platelets/
HLA antigens and the transmission of infection. Any patient
who is medically fit for elective surgery is fit to donate blood
preoperatively. The reductions in haematocrit and blood
viscosity that accompany preoperative donation improve
microcirculation and tissue perfusion, and reduce the risk of
thromboembolism.
8
However, PAD is associated with increased risk of donation
(severe vasovagal reaction and angina, or trauma due to
the venepuncture) and wastage of unused units.
9
To reduce
these, the medical exclusion criteria adopted by the British
Committee for Standards in Haematology (BCSH) are
advocated. The patient should be free from cardiovascular,
cerebrovascular and respiratory diseases, and active infections;
the patient should also have a confirmed and reliable surgical
date, have good venous access and also be free from anaemia.
Autologous blood transfusion – a review
TEDDY CHARLES ADIAS, PH.D., A.M.L.S.C.N., A.I.B.M.S.
ZACHEUS JEREMIAH, M.SC., A.M.L.S. C.N.
Department of Medical Laboratory Science, Rivers State University of Science and Technology, Port Harcourt,
Nigeria
EMMANUEL UKO, PH.D., F.M.L.S.C.N.
Department of Haematology and Blood Transfusion, University of Calabar, Nigeria
ERHABOR OSARO, PH.D., A.M.L.S.C.N., A.I.B.M.S.
Department of Haematology and Blood Transfusion, University of Port Harcourt Teaching Hospital, Nigeria
General Surgery
Summary
The discovery of HIV and other transfusion-transmissible
infections has increased the demand for alternatives to
allogeneic blood transfusion. One such alternative is
autologous transfusion. This review presents an analysis
of autologous transfusion. We conclude that autologous
transfusion should form part of a strategy to minimise
the risk associated with allogeneic transfusion in Nigeria
and other developing countries.
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Pregnancy with impaired placental blood flow, intrauterine
growth retardation, pregnancy-related hypertension, pre-
eclampsia, renal disease, and insulin-dependent diabetes
mellitus are other relative contraindications.
10,11
Acute normovolaemic haemodilution (ANH)
Acute normovolaemic haemodilution (‘haemodilution’) is a
form of autologous donation performed preoperatively in the
operating theatre or anaesthetic area. It is usually restricted
to patients in whom substantial blood loss (> 1 litre or 20%
of blood volume) is predicted. Whole blood (1.0 - 1.5 l) is
removed, and simultaneously intravascular volume is replaced
with crystalloid or colloid, or both, to maintain blood volume.
The anticoagulated blood is then reinfused during or shortly
after surgical blood loss has stopped in reverse order of
collection.
1
The blood-sparing benefit of haemodilution is
the result of the reduced red cell mass lost during surgical
bleeding.
Patients of any age may be considered for ANH. ANH
should only be considered when the potential blood loss is
likely to be greater than 20% of blood volume. It should not
be considered unless the preoperative haemoglobin (Hb) is
> 11g/dl.
11
The amount of blood withdrawn depends on the
target haematocrit and can be calculated using a standard
formula, viz. V = EBV x (H
o
– H
f
)/H
av
(where V = volume to
be removed, EBV = estimated blood volume (usually taken as
70 ml/kg body weight), H
o
= initial H
b
, H
f
= desired H
b
and
H
av
= average H
b
(mean of H
o
and H
f
)).
Haemodilution combines the advantages of PAD and
some additional benefits, with controversies. Elaborate
mathematical modelling studies have been published that take
into account the dynamic nature of the patient’s red blood
cell (RBC) mass as it affects blood loss, fluid replacement,
and blood transfusions.
12
Haemodilution is probably less
expensive to accomplish than PAD, and it may be the only
option available when surgery is performed in other than
elective settings.
13
In orthopaedic and cardiovascular surgery,
reductions in allogeneic blood use have been reported after
extreme haemodilution.
14
More modest haemodilution
may also be beneficial,
15
but this is not accepted by all.
12
The severity of the anaemia could affect oxygen transport,
although the concomitant drop in blood viscosity, and
compensatory cardiac output increase, could restore
oxygen delivery. However, one group has suggested that
haemodilution may jeopardise patients at risk for myocardial
infarction.
9
Perioperative cell salvage (PCS)
Intraoperative RBC salvage entails the collection and
reinfusion of blood lost during or after surgery. Shed blood
is aspirated from the operative field into a specially designed
centrifuge. Citrate or heparin anticoagulant is added, and the
contents are filtered to remove clots and debris. Centrifuging
concentrates the salvaged red cells, and saline washing may
be used. This concentrate is then reinfused. Devices used
can vary from simple, inexpensive, sterile bottles filled with
anticoagulant to expensive, sophisticated, high-speed cell
washing devices. Postoperative salvage refers to the process
of recovering blood from wound drains and reinfusing the
collected fluid with or without washing.
1
Many surgical patients who undergo procedures in which
transfusions are likely can benefit from intraoperative blood
salvage, especially where PAD is impossible or inadequate.
8
Relative contraindications to the use of PCS include
infection (contamination of the operative field by bacteria)
and presence of malignant cells. However recent published
work suggests that the risk of dissemination of malignant
disease is minimal.
9
Patients undergoing cell salvage need
not be screened for viral markers. Universal precautions to
protect staff from the risks of virus transmission must always
be observed.
11
The haematocrit of salvaged unprocessed blood is typically
low because of a combination of dilution from irrigation
fluids and some degree of mechanical haemolysis.
16
After
blood has been exposed to serosal surfaces in operative fields,
it becomes depleted of coagulation factors and platelets;
ARTICLES
TABLE I. DIRECT COST OF ALLOGENEIC BLOOD TRANSFUSION AND VARIOUS FORMS OF AUTOLOGOUS
BLOOD TRANSFUSION
Cost per unit (US$)
Item Allogeneic PAD ANH PCS
Collection
Labour 1.41 2.1 0.7 4.2
Equipment 2.82 3.5 2.82 6.3
Infectious disease
testing*
Initial 11.9 - - -
Confirming 6.3 - - -
Blood processing and
inventory management
Labour 2.82 2.82 2.1 2.82
Equipment 1.42 1.41 3.5 1.41
Compatibility testing
Labour 3.5 - - -
Equipment 2.82 - - -
Total 32.99 9.83 9.12 14.73
*Blood is tested for syphilis, hepatitis B surface antigen, antibodies to hepatitis B core antigen, antibodies to hepatitis C virus, antibodies to HIV 1 and 2.
PAD = predeposit autologous donation; ANH = acute normovolaemic haemodilution; PCS = perioperative cell salvage.
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a clinical consequence termed ‘salvaged blood syndrome’
has been described, which involves multiorgan failure and
consumption coagulopathy.
1
Nevertheless, renal sequelae are
uncommon.
17
Qualitative coagulation abnormalities often
observed in recipients of large volumes of salvaged blood
include hypofibrinogenaemia, elevated fibrin degradation
products, thrombocytopenia, and prolonged prothrombin and
partial thromboplastin times.
18
During open-heart operation,
mediastinal blood may contain very high levels of cardiac
muscle enzymes, especially creatine phosphokinase, as well
as lactate dehydrogenase from haemolysed RBCs.
19
The
reinfusion of shed mediastinal blood can result in increased
levels of these enzymes and can confound the diagnosis of
myocardial infarction in the postoperative period.
20
Salvage is a safe and efficacious alternative to allogeneic
red cell transfusion if standards are maintained, but fewer
data are available on clinical outcomes than for PAD and
ANH. These techniques offer advantages similar to those of
haemodilution but do not require infusions of crystalloid or
colloid to preserve blood volume. Many litres of blood can
be salvaged intraoperatively during extensive bleeding, far
more than with other autologous techniques. Intraoperative
salvage is used extensively in cardiac surgery, trauma
surgery, and liver transplantation. Salvage can be one of
the most expensive autologous techniques because costly
capital equipment and disposables are used, and it is usually
restricted to procedures resulting in substantial blood loss (>
1 - 2 l).
1
Data on clinical outcomes
Blumberg et al.
1
evaluated 16 observational studies and
concluded that autologous blood transfusion is associated
with significant reductions in postoperative infection.
The number of randomised studies is low; a PUBMED
search revealed only 5. Patients randomised to receive
autologous rather than allogeneic blood had better clinical
outcomes (reduction in postoperative infection and
recurrence of cancer) in 4 of 5 studies.
3,21-23
In the only study
that supported allogeneic transfusion over autologous, one-
third of the patients randomised to receive autologous blood
transfusion also received allogeneic blood because allowable
blood loss was exceeded.
24
Few data exist comparing the relative advantage
of the various forms of autologous transfusion. Ness et
al.
15
randomised 50 patients to donate PAD of 3 units of
red cells or to undergo ANH before radical retropubic
prostatetectomy. They found that ANH could safely replace
or augment PAD as a means of decreasing the use of
allogeneic blood, and they consider their results applicable
to any surgical procedure in which a 1 000 ml blood loss
is anticipated. In a randomised trial of patients undergoing
total knee arthroplasty who predonated either 1 unit of blood
for unilateral, or 2 units for bilateral knee procedures, or
who underwent ANH to a haematocrit of 28%, Goodnough
et al.
25
found no differences in the amount of allogeneic
blood transfusions among the PAD and ANH cohorts for
all 32 patients. A meta-analysis of all 24 eligible prospective
randomised trials (1 218 patients) comparing ANH with
control groups showed that ANH effectively reduced the
likelihood of exposure to at least 1 unit of allogeneic blood in
cardiac and miscellaneous procedures but not in orthopaedic
surgery. The overall results of this analysis were inconclusive
since sample sizes were small, variable amounts of blood were
drawn,
26
and trials involving different surgical procedures had
to be pooled.
27
Data from randomised studies confirm the results of
observational studies and the comparative advantage of
autologous blood transfusion over allogeneic blood
transfusion.
Cost of autologous blood transfusion
Comparative cost data on the various forms of autologous
blood transfusion are rather subjective and inconsistent; the
body of literature to date on cost effectiveness compared
allogeneic with autologous blood transfusion. Most of such
studies concluded that allogeneic is more cost effective than
autologous blood transfusion.
9,28
The increased cost comes
from unused autologous collection; this problem is magnified
by over-collection and unnecessary utilisation, and by the
extra work involved in deviation from routine large-scale
allogeneic collection practices.
9
In our setting, we evaluated a hypothetical cost estimate
by considering the direct cost accruable for each unit
of allogeneic blood transfused and the various forms of
autologous blood transfusion procedures. Table I gives a
summary of the direct cost for the various procedures less the
cost of units discarded and the cost of treating complications
of transfusion. Generally, direct cost was estimated by
computing the resources required for donor recruitment,
infectious disease testing, phlebotomy, cross-matching,
administrative and inventory management, and overhead
cost. It is obvious from our estimate that an autologous blood
transfusion procedure enjoys comparative advantage over
allogeneic blood transfusion per unit of transfusion.
In one hypothetical cost-utility analysis of patients
undergoing primar y elective hip replacement, cost-
effectiveness of transfusion per quality-adjusted life-year
(QALY) was estimated at an extremely high $3 400 000.
However, if allogeneic transfusion was assumed to increase
the risk of postoperative bacterial infection, a possibility
suggested by some workers,
2,4
the cost of using autologous
blood fell to less than $50 000 per QALY, and the procedure
became dominant (cheaper to use than allogeneic blood) as
the infection risk rose.
29
However, it should be recognised
that transfusion medicine in sub-Saharan Africa is practised
in a setting that is inherently risk-averse, owing, of course, to
heightened public awareness of HIV and other transfusion-
transmissible viruses, given their high prevalence and the
absence in most of our settings of molecular technologies for
earlier and proper detection. In the context of our limitations,
it might be erroneous to accept cost effectiveness strictly
on the basis of programmes that are less expensive and
more effective, but also to accept even programmes that
are more expensive and more effective because it is the
subjective health outcome that is paramount. Otherwise,
how do we compensate for all the negative consequences of
immunomodulation and fears?
Conclusion
An autologous blood transfusion programme must be reliable,
effective and safe for patients and practitioners. A hospital
wanting to establish an autologous blood transfusion service
requires the total commitment of those involved. The essence
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of success is motivation and communication and the planning
involves all key players. It is quite likely that many of our
patients will appreciate the value of autologous transfusion.
Although there are considerable organisational problems to
overcome, and the need for a strong sense of commitment,
the setting up of an autologous blood transfusion service to
meet this demand can only be beneficial. Our colleagues will
have to be educated to promote the concept that the use of a
person’s own blood is safest. It will conserve donor blood for
those who need it, and result in more effective use of blood
supplies. An autologous blood transfusion programme should
only be complementary to the established blood transfusion
programme. We can make this work even in our centres.
First, appreciate the concept; make further investigation with
regard to cost benefit; motivate for the establishment of a
transfusion committee, then policy; and sell the idea with
facts. Let us speak to be heard!
REFERENCES
1. Blumberg N, Vanderlinde ES, Heal JM. Autologous transfusion.
BMJ 2002;
324: 772-775.
2. Blumberg N, Heal JM. Effects of transfusion on immune function – cancer
recurrence and infection. Arch Pathol Lab Med 1994; 118: 371-379.
3. Heiss MM, Mempel W, Delanoff C,
et al. Blood transfusion-modulated
tumor recurrence: first results of a randomised study of autologous versus
allogeneic blood transfusion in colorectal cancer surgery. J Clin Oncol 1994;
12: 1859-1867.
4. Houbiers JG, van de Velde CJ, van de Watering LM,
et al. Transfusion of
red cells is associated with increased incidence of bacterial infection after
colorectal surgery: a prospective study. Transfusion 1997; 37: 126-134.
5. Sloand E, Kumar P, Klein HG, Merritt S, Sacher R. Transfusion of blood
components to persons infected with human immunodeficiency virus type
1: relationship to opportunistic infection. Transfusion 1994; 34: 48-53.
6. Kirkley SA. Proposed mechanisms of transfusion-induced
immunomodulation. Clin Diagn Lab Immunol 1999; 6: 652-657.
7. Kirkley SA, Cowles J, Pellegrini VD,
et al. Increased T helper 2 (Th2) type
cytokine secretion in surgical patients receiving allogeneic transfusions.
Transfus Med 1998; 8: 195-204.
8. Parker-Williams EJ. Autologous blood transfusion.
Postgraduate Doctor
1989; 11: 52-56.
9. Kruskall MS. Autologous blood transfusion and related alternatives to
allogeneic transfusion. In: Hillyer CD, Silberstein LE, Ness PM, et al. eds.
Blood Banking and Transfusion Medicine. 1st ed. Philadelphia: Churchill
Livingstone, 2003: 273-282.
10. Voak D, Finney RD, Forman P,
et al. Guidelines for autologous transfusion.
I. Preoperative autologous donation. British Committee for Standards in
Haematology and Blood Transfusion Task Force. Autologous Transfusion
Working Party. Transfus Med 1993; 3: 307-316.
11. Napier JA, Bruce M, Chapman J,
et al. Guidelines for autologous transfusion.
II. Perioperative haemodilution and cell salvage. British Committee for
Standards in Haematology and Blood Transfusion Task Force. Autologous
Transfusion Working Party. Br J Anaesth 1997; 78: 768-771.
12. Brecher ME, Rosenfeld M. Mathematical and computer modeling of acute
normovolaemic haemodilution. Transfusion 1994; 34: 176-179.
13. Monk TG, Goodnough LT, Brecher ME,
et al. Acute normovolaemic
haemodilution can replace preoperative autologous blood donation as a
standard of care for autologous blood procurement in radical prostatectomy.
Anesth Analg 1997; 85: 953-958.
14. Weiskopf RB. Mathematical analysis of isovolaemic haemodilution indicates
that it can decrease the need for allogeneic blood transfusion. Transfusion
1995; 35: 37-41.
15. Ness PM, Bourke DL, Walsh PC. A randomised trial of perioperative
haemodilution versus transfusion of preoperatively deposited autologous
blood in elective surgery. Transfusion 1992; 89: 226-230.
16. Aaron RK, Beazley RM, Riggle GC. Haematologic integrity after
intraoperative allotransfusion: Comparison with bank blood. Arch Surg
1974; 107: 831-837.
17. Brener BJ, Raines JK, Darling RC. Intraoperative autotransfusion in
abdominal aortic resection. Arch Surg 1973; 107: 78-84.
18. Stillman RM, Wrezlewicz WW, Stanczewski BS,
et al. The haematological
hazards of autotransfusion. Br J Surg 1976; 63: 651-654.
19. Griffith LD, Billman EL, Breslich DJ,
et al. Apparent coagulopathy caused
by infusion of shed mediastinal blood and its prevention by washing of the
infusate. Ann Thorac Surg 1989; 47: 400-406.
20. Schmidt H, Mortensen PE, Folsgaard SL, Jensen EA. Cardiac enzyme and
autotransfusion of shed mediastinal blood after myocardial revascularization.
Ann Thorac Surg 1997; 63: 1288-1292.
21. Newman JH, Bowers M, Murphy J. The clinical advantages of autologous
transfusion. A randomised controlled study after knee replacement. J Bone
Joint Surg Br 1997; 79: 630-632.
22. Farrer A, Spark JI, Scott DJ. Autologous blood transfusion: the benefits to
the patient undergoing abdominal aortic aneurysm repair. Journal of Vascular
Nursing 1997; 15: 111-115.
23. Thomas D, Wareham K, Cohen D, Hutchings H. Autologous blood
transfusion in total knee replacement surgery. Br J Anaesth 2001; 86: 669-
673.
24. Busch ORC, Hop WCJ, Hoynck van Papendrecht MAW,
et al. Blood
transfusion and prognosis in colorectal cancer. N Engl J Med 1993; 328:
1372-1376.
25. Goodnough LT, Monk TG, Despotis GJ, Merkel K. A randomised trial of
acute normovolaemic haemodilution compared to preoperative autologous
blood donation in total knee arthroplasty. Vox Sang 1999; 77: 11-16.
26. Bryson GL, Laupacis A, Wells GA. Does acute normovolaemic haemodilution
reduce perioperative allogeneic transfusion? A meta-analysis. Anesth Analg
1998; 86: 9-15.
27. Rosenblatt MA. Strategies for minimising the use of allogeneic blood during
orthopaedic surgery. Mt Sinai J Med 2002; 69: 83-87.
28. Etchason J, Petz L, Keeler E,
et al. The cost-effectiveness of preoperative
autologous blood transfusion donation. N Engl J Med 1995; 332: 719-724.
29. Sonnenberg FA, Gregory P, Yomtovian R,
et al. The cost-effectiveness
of preoperative autologous blood transfusion revisited: Implication of an
increased risk of bacterial infection with allogeneic transfusion. Transfusion
1995; 39: 808-817.
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