Management of women who decline blood and blood products in pregnancy

Introduction
Fears regarding the safety of blood product
transfusion and concerns about the cost and
limited supply have prompted all specialties to
consider alternatives.This subject is especially
important in obstetrics, where haemorrhage can
occur rapidly and clinical estimations of blood loss
are notoriously inaccurate.1,2 In pregnancy, some
women choose to decline blood and blood
products: in one study3 of 228 women attending
antenatal clinics over a 7-day period, 8% (n18)
stated that they would not want a blood
transfusion, specifying reasons including religion
and risk of infection.There is, therefore, variation
in what is acceptable to individual women and to
what extent they are prepared to go to avoid
transfusion, including death.
Women who decline blood
for safety concerns
The risks of blood transfusion include incorrect
blood component transfusion, transfusion-related
acute lung injury, other immune complications
and transfusion-transmitted infections.4 Serious
Hazards of Transfusion (SHOT) is a voluntary,
confidential scheme that compiles reports of
adverse events resulting from transfusion of blood
and blood components in the UK. The data are
accessible on the internet in a language
understandable to most women.
In the 10-year period between 1996–2006, 2630
incidents were reported to SHOT and over 4800
‘near miss’ events were analysed. In 2006 alone,
there were four deaths attributable to transfusion
in the UK:4 two resulted from incorrect
prescribing, one from transfusion of platelets
contaminated with Klebsiella pneumoniae and one
from transfusion-related acute lung injury.Despite
intensive donor screening, the potential for
unrecognised transmission of pathogens still
remains, particularly those associated with
asymptomatic illness during a ‘window’ period.
Up until 2007, there have been four reports of
variant Creutzfeldt-Jakob disease in recipients of
blood transfusion in the UK.5 There is now
increasing public demand in the USA, Canada and
Europe for alternatives to blood transfusion:6,7 so
much so that patients have even falsely presented
themselves as Jehovah’s Witnesses to avoid blood
transfusion.8
Women who decline blood
for religious reasons
The principal group of women known to decline
blood and blood products are the Jehovah’s
Witnesses, members of a Christian group that has
over 6.5 million members worldwide,with an
estimated 130 000 living in the UK.9 They base
their refusal of blood on the literal interpretation
of certain biblical verses. This is a deeply held core
belief and administration of blood or blood
products to a Jehovah’s Witness against their
wishes would be regarded as a gross physical
violation.However, although Jehovah’s Witnesses
do not accept the use of whole blood or primary
blood components (red cells, platelets or plasma),
the decision as to whether to accept clotting
factors, autologous transfusion or
immunoglobulin products such as anti-D is an
individual one.Autologous pre-deposit is never
acceptable to Jehovah’s Witnesses, but a
transfusion circuit that can be maintained in
continuity with the woman’s (cell salvage, for
example) may be acceptable.
The cost and supply of blood
The cost of blood has increased from £40 for one unit
of red cells in 1998 to £140 in 2006, mostly because
of the use of leucodepletion to reduce the risk of
infection. In 2006, over 2.3 million red cell units
were issued in the UK, costing over £200 million.4
The supply of blood has been reduced by policies
designed to improve blood safety; for example,
anyone who has received a blood transfusion
since 1980 is now excluded from the donor pool
to reduce the risk of variant Creutzfeldt-Jakob
disease.
How much blood do we use
in obstetrics?
It has been reported that obstetrics accounts for
approximately 3% of all blood (red cells)
transfused in the UK.10 A prospective study11 of
57 000 women undergoing caesarean section in the
USA found a red cell transfusion rate of 2.2–3.2%,
with a median of 2 units being transfused.
Transfusion was strongly associated with
preoperative anaemia,with an odds ratio of
17.0–19.9 for women with a haematocrit 25%.
What are the consequences of
declining blood transfusion?
Deaths in obstetrics are rare and it is estimated that
the mortality rate from haemorrhage is 0.66 per
100 000 maternities in the UK. The seventh report
of the Confidential Enquiries into Maternal Deaths
in the United Kingdom12 documented 17 direct
deaths from haemorrhage in 2003–05,with
haemorrhage complicating nine other maternal
deaths. Since 1985, there have been ten deaths
associated with refusal to accept blood transfusion
in cases of massive obstetric haemorrhage13
(including three fatalities in the most recent
report) and it is likely that these women would
have survived had they agreed to receive blood.
Two large series assessing the obstetric outcomes of
Jehovah’s Witnesses in the USA14 and the UK15
reported a 44-fold and 65-fold increased risk of
death, respectively, in these women, while the
report on Confidential Enquiries into Maternal
Deaths in the United Kingdom 1991–199316
estimated the maternal mortality of women who
declined blood to be 100 times higher than that of
the general population. In the 12-year study14 of
391 deliveries to Jehovah’s Witnesses in New York,
there was a 6% (n24) rate of postpartum
haemorrhage,with two maternal deaths and one
woman changing her mind about receiving
blood products. The 14-year observational
study15 reviewing 116 deliveries in a single centre in
London noted a postpartum haemorrhage rate of
6% (n7),with one maternal death and four
women changing their minds and consenting to
the use of blood products. Fortunately, most
women who decline blood will not die but there is
a paucity of data on morbidity associated with
declining blood. In fact, the most common
morbidity documented in the aforementioned
studies of Jehovah’s Witnesses was anaemia,with
almost a quarter of the mothers having postdelivery
haemoglobin levels of11 g/dl.15
Legal issues
In the UK, the law is clear on the issue of women
who refuse blood transfusion: a woman may
decline any treatment even if this would lead to her
demise as long as she is competent and does so
voluntarily, no matter how unusual her decision
may appear.17Moreover, no-one is allowed to
refuse treatment on behalf of another competent
adult.Advance directives are legally valid and to
administer blood to a woman carrying a
‘no blood’ advance directive would constitute
battery.What is crucial is that the health worker is
satisfied that the circumstances of the advance
directive are currently applicable and that it was
carried out autonomously. In an emergency,
however, if there is no objective evidence of the
woman’s beliefs, the doctor must act in the best
interests of the woman following discussion with
her relatives to gain further information regarding
her beliefs, practices and state of mind.
Ethical issues
Many ethical issues arise from women declining
blood transfusion in pregnancy and the two that
we would like to highlight here are:
• the woman’s autonomy
• the ethics of the current practice of reserving
blood conservation techniques for women who
decline blood.
In such women there is a conflict between
beneficence (in that the healthcare team’s objective
is to provide the best physical care for the mother
and fetus) and the woman’s autonomous decision
to decline treatment. Although respect for
autonomy is now taught and understood as a
fundamental principle of clinical medicine in the
UK, one should not underestimate how traumatic
it could be for healthcare staff involved in the death
of a woman who has declined blood products.
In the case of Jehovah’s Witnesses, what is and is
not acceptable is open to debate and it is important
to treat women individually with regard to their
personal beliefs and preferences, as opposed to
treating all such women according to a blanket
policy from the Church.18 Some Jehovah’s
Witnesses, for example, believe that the biblical
passages have been misinterpreted: they support
the individual’s choice to accept blood and
conscientiously reject official Watchtower Society
blood policy.19
The second ethical issue is whether the woman
who declines blood receives better obstetric care,
led by senior obstetricians: she has intensive
antenatal improvement of haematinics, her
delivery is as bloodless as possible, and she has
access to technology such as cell salvage (which
may be safer than allogeneic blood transfusion).
It may be argued that one should be providing this
optimal level of care as standard and perhaps this
would prove more cost-effective and help preserve
our dwindling stocks of donor blood. One further
question is whether one should proactively offer
bloodless management, as is currently practised
by some hospitals in the USA, which offer formal
bloodless surgery programmes,20 or arrange these
only on women’s request (as in the UK).
Antenatal management
Preconceptual care
Antenatal care begins preconceptually;
optimisation of haemoglobin levels should begin
well in advance of pregnancy and risk factors for
postpartum haemorrhage such as grand
multiparity should be identified.
Booking
When women first present to antenatal services
they should be asked whether they would accept a
blood transfusion. If they are unsure, or state that
they would decline, this should prompt a
discussion as to the reasons and the implications.
Women who decline blood are classified as high
risk and should be triaged to consultant care.
Routine booking bloods, including a full blood
count and ‘group and save’, should be taken. It is
important that women understand why a ‘group
and save’ sample is taken and that a full and
frank discussion about anti-D takes place in
rhesus-negative women, including the fact that it
is obtained from human blood products.
Advance directives
Women who decline blood should be encouraged
to complete an advance directive (Figure 1), which
is a legally binding document. Depending on their
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Figure 1
Advance directive declining blood
and blood products
reasons for refusal,women need to have a basic
understanding of the function of different blood
components to be able to specify their precise
wishes. They may not have considered where to
draw the line and whether, for example,
immunoglobulin or clotting factors would be
acceptable. It is also important to consider
confidentiality and to appreciate that the woman’s
stated preferences may be influenced by the person
accompanying her.
Optimising iron stores
Antenatal anaemia secondary to iron deficiency
is usually treatable with oral iron, although
parenteral iron may be helpful in resistant cases
or late bookers. Intravenous iron sucrose complex
has been found to increase the rate of rise in
haemoglobin in pregnant women more rapidly
than oral ferrous sulphate,with no documented
serious adverse effects.21 In resistant cases,
recombinant human erythropoietin (rhEPO),
which does not cross the placenta, has been used
antenatally and found to be safe and aceptable.22,23
A randomised prospective study from
Switzerland24 allocated 40 women with resistant
iron deficiency anaemia to receive either twiceweekly
intravenous iron sucrose plus rhEPO or
twice-weekly iron sucrose alone and found both
regimens effective (although women who had
rhEPO achieved their target haemoglobin more
rapidly). In Singla et al.’s14 observational study of
Jehovah’s Witnesses in the USA, all 166 women
with low haematocrit at 28 weeks were offered
erythropoietin but the 6 (4%) who accepted had a
nonsignificant rise in haematocrit compared with
those who declined. Erythropoietin cannot yet be
recommended outside clinical trials because of
limited data, but there are case reports describing
its use in high-risk Jehovah’s Witness patients.25
Identifying risk factors for haemorrhage
In the most recent report from the Confidential
Enquiries into Maternal Deaths in the United
Kingdom,12 three of the 17 maternal deaths directly
attributable to haemorrhage were associated with
placenta praevia, therefore, placental site should be
assessed in women who decline blood transfusion.
Magnetic resonance imaging can aid in diagnosis if
there is suspicion of placenta accreta.26 It is also
worth noting that the presence of fibroids can
increase the risk of postpartum haemorrhage,with
an odds ratio of 2.57 (95% CI 1.54–4.27).27
Concomitant clotting disorders or use of
anticoagulant or antiplatelet drugs should be
reviewed.
Planning for delivery
For women who decline blood products, it may be
preferable for them to travel to a regional centre with
intensive care, cell salvage facilities, recombinant
factor VII, interventional radiology and staff who are
familiar with the management of women who
decline blood products. There are currently 27
university hospitals in England, Scotland and Wales28
that are able to provide transfusion-alternative
treatments, compared with over 150 blood
conservation centres in the USA, including the
well-known Regional Center for Blood Conservation
at St Vincent Charity Hospital (see Websites).
Blood conservation techniques
Available blood conservation techniques should
be discussed in advance and their acceptability
recorded in the advance directive. Below are brief
descriptions of techniques that can potentially be
used in pregnancy.
Intraoperative cell salvage
Red blood cell salvage involves retrieval of
exsanguinated blood during operative or vaginal
delivery,which is then washed, filtered and
resuspended in saline in preparation for
transfusion. In Jehovah’s Witness patients the
system is set up as a continuous ‘loop’which is
pre-primed and run without disconnection until
the end of the procedure. The main theoretical
safety concerns are amniotic fluid embolism and
fetomaternal isoimmunisation in future
pregnancies.To minimise fetal contamination of
the maternal circulation, a leucocyte depletion
filter is used,with separate suction being used for
amniotic fluid.Anti-D immunoglobulin should be
administered postpartum for rhesus-negative
women using cell salvage.A review article5 which
included 400 obstetric cases compiled from case
reports, a retrospective case series (n64), a
historic cohort study (n139) and a prospective
controlled trial (n34 in the cell salvage arm)
suggested that there were no serious maternal
complications that could be directly attributable
to its use. Thus several bodies, including the Centre
for Maternal and Child Enquiries (CMACE),29
the American College of Obstetricians and
Gynecologists,30 the Obstetric Anaesthetists’
Association/Association of Anaesthetists of
Great Britain and Ireland31 and the National
Institute for Health and Clinical Excellence32
have endorsed the use of cell salvage in obstetric
patients, even in women who are willing to accept
allogeneic blood.
Acute normovolaemic haemodilution
This technique,which may be acceptable to some
Jehovah’s Witnesses, involves the removal of
whole blood from the woman immediately
preoperatively whilst simultaneously infusing
colloid and/or crystalloids. This maintains the
circulatory volume but reduces the haematocrit,
thus resulting in a smaller red cell mass loss during
surgery.However, there is some concern over
whether acute normovolaemic haemodilution in
pregnancy could precipitate cardiac failure or
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cause placental insufficiency33 and this technique
is probably not adequate in massive obstetric
haemorrhage. A meta-analysis of 42 trials34 showed
that the quality of published literature was
insufficient to recommend a firm conclusion on
the efficacy or safety of acute normovolaemic
haemodilution, particularly in an obstetric setting.
Perioperative autologous donation
Note that this technique has no role in emergency
obstetric haemorrhage and is not acceptable to
Jehovah’s Witnesses. This technique may have a
limited use in women having elective caesarean
section who are at a high risk of bleeding and in whom
there are exceptional cross-matching difficulties.
CMACE/RCOG guidelines
The Centre for Maternal and Child Enquiries35 and
the RCOG36 have published guidance regarding the
management of pregnancy in women who decline
blood products.
In the seventh report of the Confidential Enquiries
into Maternal Deaths in the United Kingdom,12 it
was reported that:
Consultant and anaesthetic involvement is
necessary during the antenatal period in order
to develop a care plan together with the woman,
her husband and family,and,if necessary,
religious advisors,should any difficulty occur.
Informed consent for red blood cell salvage
during surgery and infusion of salvaged blood
should be sought and clearly recorded in the
case notes. This facility should be provided for
all women who give consent for this procedure.
All women who are known to have stated a
wish not to receive blood products should
be seen by a consultant obstetrician and
anaesthetist at the onset of their labour and
a final care plan developed.
Intrapartum management
It is important to confirm with the woman that
the wishes she has expressed in an advance
directive are still strongly held. If the woman has
not previously attended for care, the above
ground needs to be covered thoroughly and
quickly with attention paid to documentation.
Senior obstetric, anaesthetic, midwifery and
haematology staff should be informed once the
woman has arrived in labour and intravenous
access and a full blood count obtained. If the
woman has consented to cell salvage, the machine
should be brought to the labour ward and staff
trained in its use informed.
In Why Mothers Die 2000–2002. The Sixth Report
on Confidential Enquiries into Maternal Deaths in
the United Kingdom,29 it is suggested that a
consultant obstetrician either performs or directly
supervises the caesarean section if the procedure is
indicated.
Postpartum management
Active management of the third stage reduces the
risk of postpartum haemorrhage by around 60%37
and it is important that the woman must not be left
unattended for the first hour.12 Perineal damage
should be repaired promptly and the birth attendant
should be vigilant for postpartum haemorrhage.
In women whose cases are further complicated by
an additional risk of bleeding, such as placenta
praevia or complicated caesarean, elective
interventional radiological techniques should be
considered. The RCOG recommends:38
…all obstetric units to consider early or
prophylactic interventional radiology as
an important tool in the prevention and
management of postpartum haemorrhage.
Arterial balloon occlusion and embolisation
can prevent major blood loss, obviating
the need for blood transfusion and
hysterectomy. Potentially, this may reduce
the need for intensive care and decrease
maternal morbidity and mortality.
Aggressive treatment of postpartum haemorrhage
Massive obstetric haemorrhage should be
anticipated and managed aggressively. In addition
to standard pharmacological treatment for
uterine atony, insertion of intrauterine
compression balloons39 (such as the Bakri SOS
balloon, Cook Ireland Ltd, Limerick, Republic
of Ireland) and the use of uterine compression
sutures40 (such as the B-Lynch suture) should be
considered.Uterine or iliac artery embolisation
or ligation38 may be attempted before proceeding
to caesarean hysterectomy. The crucial difference
in managing women who decline blood is that
there should be a lower threshold for medical and
surgical management, including hysterectomy.
Novel approaches, such as the use of Bakri
balloons placed intravaginally to control
intractable bleeding secondary to genital tract
injury in women who decline blood transfusion,
have been described.41 Non-standard
pharmacological treatments, such as the use of
recombinant factor VIIa,42 may also be considered
or planned in advance with the haematologist.
Treating postpartum anaemia
The British Committee for Standards in
Haematology does not recommend transfusion
unless the haemoglobin level is 7 g/dl;43 healthy
women can tolerate an acute drop in haemoglobin
to 5 g/dl.Anaemia can be treated with iron; in a
randomised controlled trial in Oxford44 the
haemoglobin concentration in women with
postpartum iron deficiency anaemia showed a
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faster rise in the first 6 weeks with twice daily oral
ferrous sulphate compared with two doses of
intravenous ferrous sucrose, although there was no
significant difference thereafter. Similarly, a
randomised controlled trial45 of 60 patients in
Switzerland comparing rhEPO plus iron sucrose
versus iron therapy alone showed greater increases
in haematocrit after rhEPO plus parenteral iron
than in the latter group.
Conclusion
Originally developed to serve the Jehovah’s
Witness population,whose religious beliefs
prohibit blood transfusions, blood conservation
techniques now help address patient fears about
transfusions and health service concerns about the
rising cost of blood.Methods used to avoid the
adverse events associated with allogeneic
transfusion (often grouped under the umbrella
term ‘bloodless’ surgery) can still be applied in the
case of pregnancy, although interventions may
need to be performed sooner than expected
because of the absence of the ‘buffer’ of being able
to transfuse red blood cells.
The healthcare worker must always show respect for
patient autonomy and of paramount importance are
antenatal counselling and planning. Intrapartum
techniques to avoid blood transfusion should
include cell salvage, balloon uterine tamponade and
early recourse to definitive surgical management in
the event of massive obstetric haemorrhage.
In the current economic climate, it may be argued
that one should provide this optimal level of care as
standard as this would prove more cost-effective
and help preserve our dwindling stocks of donor
blood. One further question is whether we should
proactively offer bloodless management as is
routinely practised by many hospitals in the USA,
or only arrange this on patients’ request as is
common in the UK.