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The Obstetrician & Gynaecologist 10.1576/toag.9.1.027.27293 www.rcog.org.uk/togonline 2007;9:27–33 Review

Review Management of women

with inherited bleeding disorders
in pregnancy
Authors Claudia Chi / Rezan A Kadir

Key content:
• Pregnancy in women with inherited bleeding disorders requires specialised and
individualised care using a multidisciplinary approach with obstetricians,
midwives, haematologists and anaesthetists.
• Childbirth presents an intrinsic haemostatic challenge in these women and
obstetricians may be the first to encounter haemorrhagic complications.
• An understanding and awareness of these disorders and close collaboration between
obstetricians and haematologists are essential in ensuring a successful outcome.

Learning objectives:
• To understand the basic principles in the obstetric management of women with
inherited bleeding disorders.
• To know the options available for prenatal diagnosis.
• To be aware of the increased risk of haemorrhagic complications in these women
and their offspring.

Ethical issues:
• Advances in prenatal diagnosis and treatment of inherited bleeding disorders
create complex dilemmas for families affected by these disorders.
Keywords: carriers of haemophilia / factor XI deficiency / preconceptual counselling /
prenatal diagnosis / von Willebrand disease
Please cite this article as: Chi C, Kadir RA. Management of women with inherited bleeding disorders in pregnancy. The Obstetrician & Gynaecologist 2007;9:27–33.

Author details
Claudia Chi MBBS Rezan A Kadir MD FRCS MRCOG
Clinical Research Fellow Consultant Obstetrician and Gynaecologist
Department of Obstetrics and Gynaecology, Department of Obstetrics and Gynaecology,
Royal Free Hospital, London NW3 2QG, UK Royal Free Hospital, Pond Street,
London NW3 2QG, UK
Email: rezan.abdul-kadir@royalfree.nhs.uk
(corresponding author)

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Review 2007;9:27–33 The Obstetrician & Gynaecologist

Introduction of von Willebrand disease. Type 1 is characterised

Inherited bleeding disorders are not common but
they are lifelong. Their prevalence and effects on
women are far greater than previously realised.
Many clinicians are not familiar with these
disorders but may encounter such women under
difficult or acute conditions. Childbirth presents a
haemostatic challenge to women who can
otherwise remain asymptomatic. Bleeding
disorders may be the underlying cause of obstetric
haemorrhage, and are often overlooked by
clinicians.
by a partial deficiency of VWF antigen. It accounts
for 70–80% of cases and is usually mild. Type 2 is
caused by a functional defect of the VWF protein. It
consists of four subtypes based on their different
pathophysiologic mechanisms (Table 2). Both types
1 and 2 are transmitted as an autosomal dominant
trait. Type 3 is characterised by a virtual absence of
von Willebrand factor and is, therefore, typically
severe. It is an autosomal recessive disorder and
affected individuals are either homozygotes or
compound heterozygotes.

This review addresses specific aspects of the Haemophilia A and B

obstetric management of women with inherited Haemophilias A and B result from deficiencies of
bleeding disorders, including prenatal diagnosis coagulation factors VIII (FVIII) and IX (FIX),
and antenatal, intrapartum and postnatal care. A respectively. They are less common than von
multidisciplinary approach to their management Willebrand disease but are the most common
with close collaboration between haematologists severe inherited bleeding disorders. They can cause
and obstetricians, at all stages, is necessary for the significant morbidity and mortality through a
delivery of the best possible care. Inherited bleeding spectrum of bleeding manifestations of various
disorders discussed in this review include von severities, for example, easy bruising, deep muscle
Willebrand disease, carriership of haemophilia A and joint haemorrhage, spontaneous or post-
and B, and factor XI deficiency, which account for surgery/post-traumatic bleeding and intracranial
almost 90% of all women with inherited bleeding bleeding. Both are X-linked recessive disorders:
disorders. Similar principles apply to the obstetric men inherit the condition and women are affected
management of other rare inherited bleeding as carriers. Haemophilia A affects 1 in 5 000 live
disorders listed in Table 1. However, because of male births and haemophilia B 1 in 30 000 live male
their rarity and the need for more specialised care, births. Carriers of haemophilia usually have a
they are not covered specifically in this review. clotting factor level around 50% of normal as they
have only one affected chromosome. However, a
Von Willebrand disease wide range of values (22–116 iu/dl) have been
Von Willebrand disease is the most common reported as a result of lyonisation (random
inherited bleeding disorder, with a prevalence of inactivation of one of each pair of X
approximately 1%.1,2 It results from either a chromosomes).3,4 Some haemophilia carriers have
quantitative or qualitative defect in von Willebrand very low factor levels and are, therefore, at risk of
factor (VWF), a large multimeric protein which severe bleeding complications.5
mediates platelet adhesion and serves as a carrier
protein for factor VIII. There are three main types Factor XI deficiency
Factor XI (FXI) deficiency is a rare inherited
Table 1
Deficient factor Estimated prevalence Therapy bleeding disorder. However, it is particularly
Rare bleeding disorders Fibrinogen 1:1 000 000 Fibrinogen concentrate common in Ashkenazi Jews, in whom the
Cryoprecipitate
Prothrombin 1:2 000 000 SD plasma
heterozygote frequency is 8%.6 FXI levels (normal
FIX complex concentrate range  70–150 iu/dl) are severely reduced (15
Factor V 1:1 000 000 SD plasma
FV and FVIII 1:1 000 000 SD plasma
iu/dl) in homozygotes and partially deficient
FVII 1:500 000 Recombinant FVII (15–70 iu/dl) in heterozygotes.7 Unlike
FVII concentrate
FX 1:1 000 000 SD plasma
haemophilias A and B, there is a poor correlation
FIX complex concentrate between bleeding tendency and FXI levels in
FXIII 1:2 000 000 SD plasma
FXIII concentrate
patients with FXI deficiency.7–8 The bleeding
SD plasma = solvent/detergent plasma
tendency can also vary in the same individual
following different haemostatic challenges. This
Table 2 Category Subtype Defect unpredictable nature of FXI deficiency makes
Classification of von Willebrand
disease
Type 1 Quantitative – levels ofVWF:Ac, VWF:Ag, and factorVIII management for pregnancy and delivery
usually 10–40 iu/dl
Type 2 2A Qualitative – deficiency of normal (high molecular
particularly difficult.
weight) VWF multimers
2B Qualitative – increased affinity for platelet-binding
protein GPIb Preconceptual counselling
2M Qualitative – decreased platelet dependent
function with normal VWF multimers
Identification of affected or carrier status should
2N Qualitative - impaired binding to factorVIII ideally be carried out before pregnancy for women
Type 3 Quantitative - levels of VWF:Ac and VWF:Ag, are
usually 1 iu/dl and factorVIII 20 iu/dl
in families with inherited bleeding disorders, to
VWF:Ac = von Willebrand factor activity; VWF:Ag = von Willebrand factor
allow appropriate preconceptual counselling and
antigen early pregnancy management. This is most

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Gestation
Prenatal testing in weeks
Non-invasive ≥10
ffDNA testing for fetal sex determination
USS fetal sex determination ≥ 15
a
Invasive
CVS 11–14
Amniocentesis ≥15
Cordocentesis 18–20
ffDNA = free fetal DNA in maternal blood; USS = ultrasound; CVS = chorionic villus sampling
a
Used to diagnose haemophilia
important for women who are carriers of
haemophilia or couples with FXI deficiency or type
3 von Willebrand disease. The preconceptual
period is important if a trial of desmopressin is
being considered.
Carrier detection for haemophilia is based on four
different methods:
1. Pedigree analysis, using the knowledge of X-
linked recessive inheritance, to assess a woman’s
risk from her position in the family tree.
Daughters of a man with haemophilia are
obligate carriers.
2. Phenotypic assessment based on assays of
plasma FVIII, FIX and, in some cases, VWF.
3. Direct gene mutation detection.
4. Indirect gene analysis involving the use of
linked polymorphic markers to track heredity
of a haemophilia gene within a pedigree when
the mutation is not known.
Direct gene analysis allows definitive diagnosis of
carrier or non-carrier status while the other
methods only ascertain risk of carriership of
haemophilia. As 20% of all people with
haemophilia A and 50% of those with severe
haemophilia have intron 22 inversion mutation,
this is the starting point of direct mutation
detection for severe cases. Mutation screening is
performed in the remaining 80%. At our centre
more than 95% of causative mutations are
currently identified through direct gene analysis.
When this not possible, linkage analysis is then
undertaken.
Preconceptual counselling has two roles. The first is
to provide women and their partners with adequate
information on the genetic implications of their
disorders, their reproductive choices and the
management of their pregnancies, including
options of prenatal diagnosis. This will assist them
to reach a decision that is appropriate to their
situation. Psychological support should be available
during all aspects of counselling with an
understanding of the ethnic and cultural influences
on each individual. The second is to allow planning
for pregnancy and to perform a trial of
desmopressin if appropriate. Other aspects of
preconceptual care include immunisation against
hepatitis A and B for those likely to require blood
© 2007 Royal College of Obstetricians and Gynaecologists
2007;9:27–33 Review
Risk of Table 3
miscarriage (%) Comments Prenatal diagnosis options for
carriers of haemophilia
- -
- First trimester (11–14 weeks) USS fetal sexing available at
certain centres in research setting
1 Known causative mutation
1 Known causative mutation
1.4 Causative mutation unknown (rarely performed today)
transfusion and general advice, for example,
regarding folic acid supplementation.
Prenatal diagnosis
Prenatal diagnosis forms an integral part of the care
provided for women and families affected by
inherited bleeding disorders. It is primarily
considered in carriers of haemophilia because of
the severity of the disorder in their male offspring
and the knowledge of genetic defects in many
affected families. In each pregnancy, carriers of
haemophilia have a 50% chance of having a male
fetus that is affected and a 50% chance of having a
female fetus that is also a carrier. Options available
for prenatal diagnosis of haemophilia are presented
in Table 3.
In von Willebrand disease the option of prenatal
diagnosis is offered when the fetus is at risk of being
affected by severe forms of the disorder, principally
type 3. Similarly, in FXI deficiency, prenatal
diagnosis is offered when there is a risk of severe
FXI deficiency in the child. Because of the large
number of different genetic mutations implicated
in FXI deficiency, prenatal diagnosis is often
difficult except in Ashkenazi Jews, in whom there
are two predominant mutations.6
Invasive methods
Invasive prenatal diagnostic methods, such as
chorionic villus sampling (CVS) and
amniocentesis, allow definitive diagnosis but are
associated with a risk of procedure related fetal loss.
CVS is the method most widely used today for the
prenatal diagnosis of haemophilia and other severe
forms of inherited bleeding disorders. It is
performed at 11–14 weeks of gestation under
ultrasound guidance. It has the advantage of earlier
diagnosis compared with amniocentesis, which is
performed at 15–20 weeks of gestation. Both are
associated with a 1% risk of miscarriage.
Cordocentesis (ultrasound guided fetal blood
sampling) is performed at around 18–20 weeks of
gestation to obtain fetal blood for clotting factor
assay. The procedure related fetal loss rate was
reported as 1.4%.9 It is rarely performed today but
can be an option for cases in which the causative
mutation cannot be identified. While prenatal
diagnosis is now widely available, the uptake rate of
termination of pregnancies affected by
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Review 2007;9:27–33
haemophilia remains low. Many carriers do not
consider haemophilia to be a sufficiently severe
disorder to justify termination of pregnancy.10
There also has been a substantial improvement in
the management of haemophilia and the quality of
life of affected individuals.
Non-invasive determination of fetal sex
When parents do not opt for invasive prenatal
diagnosis, non-invasive determination of fetal sex is
very useful in the management of pregnancies at
risk of haemophilia. The identification of male
fetuses, which have a 50% chance of being affected,
enables the management plan for labour and
delivery to be refined to avoid the use of
instrumental deliveries and invasive monitoring
techniques (for example, fetal blood sampling) in
pregnancies at risk. Fetal sex determination can be
done easily and accurately by ultrasound from the
second trimester. When performed in the first
trimester, it has the added advantage of avoiding
invasive prenatal testing (CVS) in female
pregnancies.11 Fetal sex can be determined at 11–14
weeks of gestation by ultrasound assessment of the
fetal genital tubercle.11–13 The accuracy of this
method increases with advancing gestation: from
70.3% at 11 weeks to 98.7% at 12 weeks and 100%
at 13 weeks.12
Another non-invasive method of determining fetal
sex is the analysis of free fetal DNA in maternal
circulation. Using real-time quantitative PCR,
several groups have demonstrated a 100% sensitivity
and specificity in the detection of male fetuses.11,14–15
The combined use of both methods increases the
confidence of women and clinicians in the accuracy
of these tests and provides carriers of haemophilia
with a reliable option for avoiding invasive testing in
female pregnancies.11 However, at present both tests
are still being performed in research settings and are
not yet widely available in the UK.
Preimplantation genetic diagnosis
Preimplantation genetic diagnosis is a relatively
new technique that uses in vitro fertilisation (IVF)
to create embryos. They can then be tested to
identify unaffected embryos and be selectively
transferred to the uterus. This can eliminate the
difficult decision of whether or not to terminate an
affected pregnancy. There have been reports of its
success recently in carriers of haemophilia.16 It is
likely to become a realistic option for some
individual cases in the near future. However,
further evidence on its efficacy and safety is still
required. The cost and stress of IVF also need to be
considered.
Antenatal management
Pregnancy is accompanied by various haemostatic
changes. These include a rise in levels of factor VIII
coagulant activity and von Willebrand factor
30
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antigen and activity (VWF:Ag and VWF:Ac) in
normal women, as well as in carriers of haemophilia
A and women with type 1 von Willebrand
disease.17–19 In contrast, factor IX and XI levels do not
rise significantly during pregnancy.17–18
It is vital to check clotting factor levels and arrange
prophylactic cover, if necessary, before any invasive
procedures (for example, prenatal testing or
termination of pregnancy) and in cases of
spontaneous miscarriage. These events can be
complicated by excessive or prolonged bleeding as
they commonly occur in the first trimester when
the clotting factor levels may not have risen
significantly. Treatment is not usually required in
carriers of haemophilia A and women with type 1
von Willebrand disease during late pregnancy or at
delivery, as clotting factor levels often rise to within
normal ranges. However, there is still great
variability in an individual’s haemostatic response
to pregnancy and a significant proportion can still
have low clotting factor levels at term, particularly
those with severe deficiencies.
In type 2 von Willebrand disease, FVIII coagulant
activity and VWF:Ag levels normally increase
during pregnancy, but most studies show minimal
or no rise in VWF activity with a persistently
abnormal pattern of multimers, reflecting an
increased production of abnormal VWF.19–21
Despite the increase in factor VIII and VWF
production during pregnancy, FVIII coagulant
activity levels are often low in women with subtype
2N von Willebrand disease because of impaired
binding by the abnormal VWF.21 In subtype 2B von
Willebrand disease, thrombocytopenia can develop
or worsen during pregnancy because of the
increased production of abnormal intermediate
VWF multimers which bind to platelets and induce
spontaneous platelet aggregation.22 For this reason
additional monitoring of platelet count is
recommended in women with type 2 von
Willebrand disease. Women with type 3 von
Willebrand disease show no increase in their FVIII
coagulant activity, VWF:Ag and VWF:Ac levels
during pregnancy.18
Often it is not possible to check clotting factor levels
in acute situations. Therefore, routine monitoring
of the relevant clotting factor levels should be
carried out at booking, 28 and 34 weeks of gestation
and before any invasive procedures. Testing at 28
weeks of gestation can be useful for women who
might deliver early, allowing better management,
should labour ensue. Prophylactic treatment, such
as recombinant clotting factor, clotting factor
concentrates, tranexamic acid or desmopressin,
depending on the bleeding disorder (see Table 4),
should be arranged when factor levels are less than
50 iu/dl for FVIII, FIX, VWF:Ag and VWF:Ac or less
than 70 iu/dl for FXI to cover invasive procedures,
© 2007 Royal College of Obstetricians and Gynaecologists
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Carriers of haemophilia
Von Willebrand disease
Factor XI deficiency
vWD = von Willebrand disease; VWF = von Willebrand factor; OCP = combined oral contraceptive pill
a
Where prophylactic treatment has been given, it should be extended to 3 days after vaginal delivery or 5 days following caesarean section
b
For non-breastfeeding mothers
c
For acute bleeding episodes
labour, delivery and the first few postpartum days.
It is also important to consider each individual’s
bleeding tendency, particularly in women with FXI
deficiency.
Labour and delivery
Labour and delivery are critical times for women
with inherited bleeding disorders and their affected
child as they can be exposed to various haemostatic
challenges. Delivery at a tertiary obstetric unit with
an on-site haemophilia centre is not required for all
of them. However, close liaison with the
haemophilia centre or haematologist throughout
pregnancy is essential and arrangement for delivery
should be made in advance. It is recommended that
women with a severe deficiency, or carrying an
affected/potentially affected fetus, plan the delivery
at a unit where the necessary expertise in the
management of bleeding disorders, resources for
laboratory testing and clotting factor treatments are
readily available.
Women with inherited bleeding disorders are at
increased risk of bleeding complications during
and after delivery, especially if their factor levels are
subnormal. There is some evidence that even
carriers of haemophilia with normal factor levels
have increased haemorrhagic risk compared with
non-carriers.23 At the beginning of labour, maternal
blood samples should be taken for group and save,
full blood count and coagulation screening. Factor
levels are generally not measurable in the acute
setting. Planning for delivery should be done on the
basis of the third trimester levels.
For women with low factor levels, intravenous
access should be established and prophylactic
treatment given to cover labour and delivery. The
aim of prophylactic treatment is to raise factor
levels to above 50 iu/dl for FVIII, FIX, VWF:Ag and
VWF:Ac or to 70 iu/dl for FXI for vaginal delivery
or caesarean section. Treatment options available
are shown in Tables 1 and 4. As they are specialised
therapies, they should be provided under the
supervision of a haematologist. When treatment is
required, recombinant products, if available,
should be regarded as the products of choice to
© 2007 Royal College of Obstetricians and Gynaecologists
2007;9:27–33 Review
Intrapartum/immediate postpartuma Postpartum Table 4
Treatment options for carriers of
Recombinant factorVIII or IX Tranexamic acid
haemophilia and women with von
FactorVIII or IX concentrate OCPb
Willebrand disease or factor XI
Desmopressin (↑ factorVIII only) Intranasal desmopressinc
deficiency during labour, delivery
Tranexamic acid
and in the postpartum period
Concentrate containing VWF Tranexamic acid
Desmopressin (type 1 and some type 2) OCPb
Platelets (type 2B) Intranasal desmopressinc
Tranexamic acid
Factor XI concentrate Tranexamic acid
Recombinant factorVIIa OCPb
Fresh frozen plasma
Tranexamic acid
avoid the potential risk of viral transmission.24
Desmopressin, a synthetic analogue of the
antidiuretic hormone vasopressin, increases the
plasma concentration of FVIII and VWF through
endogenous release.25–27 It is effective in selective
cases and has the advantage of avoiding the risks of
bloodborne viral infection. A test dose, often given
as part of the preconceptual assessment, is
recommended, as the response is variable between
individuals. It can be given parenterally
(intravenously or subcutaneously) or as a nasal
spray. As a result of its antidiuretic effects, there is a
risk of fluid overload and hyponatraemia.28
Therefore, fluid intake should be restricted to
1.5 litres in 24 hours with its use and repeated
administration avoided.
Regional anaesthesia/analgesia
The use of regional anaesthesia/analgesia in women
with bleeding disorders is controversial because of
the potential risk of epidural or spinal
haemorrhage and haematoma, which can lead to
permanent neurological damage. However,
provided the coagulation screen is normal and
levels of the relevant factor activity during the third
trimester is above 50 iu/dl, regional anaesthesia is
not contraindicated.17,29 In women with levels of
factor activity below 50 iu/dl or severe forms of
inherited bleeding disorders (such as type 2 and 3
von Willebrand disease and homozygote FXI
deficiency), the use of regional anaesthesia is
generally not recommended and should only be
considered after careful evaluation of the potential
risks and benefits, along with appropriate
counselling and adequate haemostatic cover. The
woman, anaesthetist, haematologist and
obstetrician should jointly make a decision on its
use in advance. An experienced anaesthetist should
perform the regional block. The extent of motor
block should be assessed frequently until the
anaesthetic has worn off and the catheter has been
removed. If the degree of motor block is more than
that expected or if it appears to be prolonged,
investigations should be carried out to check for
development of an epidural haematoma. If factor
levels cannot be checked before removal,
prophylaxis must be continued until after catheter
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removal as the pregnancy induced rise in factor
levels can quickly reverse after delivery and
bleeding in the spinal canal can then arise.
Intramuscular analgesia should be avoided in
women with bleeding disorders.
Invasive intrapartum monitoring techniques (for
example, use of a fetal scalp electrode, fetal blood
sampling) and instrumental deliveries (ventouse,
midcavity or rotational forceps) should be avoided
in pregnancies where the fetus is at risk of a
bleeding disorder, as serious head bleeding can
result from these procedures. Caesarean section
does not appear to eliminate the risk of serious
neonatal bleeding complications.30 Therefore,
normal vaginal delivery is not contraindicated in
these pregnancies. However, prolonged labour
should be avoided and delivery achieved by the least
traumatic method. Early recourse to caesarean
section should be considered to minimise the risk
of neonatal bleeding complications. Low forceps
delivery is considered less traumatic than caesarean
section when the head is deeply engaged in the
pelvis and an easy outlet delivery is anticipated.
Delivery in these cases needs to be performed by an
experienced obstetrician.
A cord blood sample should be collected from
neonates at risk of moderate or severe inherited
bleeding disorders to assess coagulation status and
clotting factor levels. This enables identification
and early management of newborns at risk of
haemorrhagic complications. If delivery has been
traumatic or if there are clinical signs suggestive of
head bleeding, a cranial ultrasound should be
performed. It is also advisable to consider
prophylactic cover in these cases. Intramuscular
injections should be avoided in neonates at risk
until the coagulation status is known. Vitamin K
should be given orally and routine immunisations
given intradermally or subcutaneously. Any
surgical procedures (for example, circumcision)
should be delayed until the coagulation status of
the neonate is known. When assessing the neonatal
clotting factor levels, it should be appreciated that
these correlate with gestational age and reach adult
levels at 6 months of age. It is, therefore, not reliable
to diagnose mild forms of inherited bleeding
disorders at birth and cord blood samples should
not be taken to diagnose these mild disorders.
Postpartum management
Women with inherited bleeding disorders are at
increased risk of haemorrhagic complications after
termination of pregnancy, miscarriage and delivery.
They are at risk of both primary and secondary
postpartum haemorrhage (PPH) because of the
rapid fall in the pregnancy induced rise in maternal
clotting factor levels (FVIII and VWF) after
delivery. The incidence of primary and secondary
PPH is increased among haemophilia carriers17
32
The Obstetrician & Gynaecologist
(22% and 11%, respectively) and women with FXI
deficiency18 (16% and 20%, respectively) compared
with the general population (5%and 0.7%,
respectively).31,32 Similarly, for women with von
Willebrand disease, primary PPH has been shown
to complicate 16–29% of pregnancies, while
secondary PPH complicates 20–29%.18–20
Bleeding complications such as PPH usually occur
in women with von Willebrand disease and carriers
of haemophilia when maternal clotting factor is low
(50 iu/dl). The risk of bleeding can, therefore, be
minimised by prophylactic treatment with
desmopressin or clotting factor concentrate when
appropriate. In women with FXI deficiency, factor
levels may not reflect the risk of haemorrhage.
Those with severely low levels or a positive bleeding
history will require prophylactic treatment,
especially if delivery is operative. The aim of
prophylactic treatment is to raise factor levels to
above 50 iu/dl for FVIII, FIX, VWF:Ag and VWF:Ac
or to 70 iu/dl for FXI during labour and delivery
and to maintain this for at least 3 days after vaginal
delivery and at least 5 days after caesarean section
(see Table 4). Care should be taken in minimising
maternal genital and perineal trauma to reduce the
risk of postpartum haemorrhage. It is also
important not to overlook the obstetric causes of
PPH.
Women with inherited bleeding disorders can
experience prolonged and/or intermittent
secondary postpartum haemorrhage.18,20
Tranexamic acid, intranasal desmopressin (in acute
episodes) or the combined oral contraceptive pill
(in non-breastfeeding women) can be used to
control this type of postpartum bleeding (Table 4).
With the average time of presentation of PPH in
women with von Willebrand disease being 15.7 ±
5.2 days,33 there is potentially the need for
prophylaxis and/or close observation for up to
several weeks postpartum.
Pregnancy is a well recognised risk factor for
venous thromboembolism (VTE). Women with
bleeding disorders have an inherently low risk for
VTE. However, bleeding disorders do not fully
protect against it.34 Thromboprophylaxis post-
delivery should be considered in the presence of
additional risk factors, especially the use of clotting
factor concentrates. Replacement therapy corrects
the coagulation defect and, therefore, is likely to
return the risk of VTE in these women closer to that
of the general population. Factor XI concentrates,
in particular, have a prothrombotic potential, hence
its concomitant use with tranexamic acid should be
avoided. There is a fine balance between the risk of
thrombosis and haemorrhage in women with
inherited bleeding disorders. Each individual
requires careful risk assessment for VTE and
general measures such as avoidance of dehydration
© 2007 Royal College of Obstetricians and Gynaecologists
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The Obstetrician & Gynaecologist
and prolonged immobility should be adopted to
minimise the risk.
Conclusion
Optimal obstetric management of women with
inherited bleeding disorders requires a good
understanding of these disorders and an awareness
of the potential maternal and neonatal
complications. A multidisciplinary team of
obstetricians, haematologists, and anaesthetists
should collaboratively formulate a prospective and
individualised management strategy.
It is generally suitable for women with a mild
bleeding disorder to have shared antenatal care
between their local obstetric unit and a tertiary
centre allied to a haemophilia centre with the
delivery planned at their local unit. However, it is
recommended for women with severe or rare
inherited bleeding disorders and those carrying an
affected, or potentially affected, fetus to deliver at a
tertiary unit with an on-site haemophilia centre.
The plan of management should be well
documented in the case notes with a copy given to
the woman to allow effective communication.
Availability of and adherence to management
guidelines help to minimise maternal and neonatal
complications. These measures collectively
improve the care provided for these women and
their pregnancy outcomes (see Box 1).
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© 2007 Royal College of Obstetricians and Gynaecologists
2007;9:27–33 Review
• Prepregnancy diagnosis and counselling
Box 1
General principles in the obstetric
• Multidisciplinary approach management of women with
inherited bleeding disorders
• Fetal sex determination and prenatal diagnosis for carriers of
haemophilia
• Clotting factor monitoring at booking, 28 and 34 weeks, prior
to any invasive procedures
• Group and save, full blood count and coagulation screen at
the onset of labour. Relevant clotting factor assay for those
with low third trimester levels who may require treatment
• Prophylactic treatment required when factor level 50 iu/dl
(FVIII, FIX, VWF). Aim to raise factor levels to above 50 iu/dl
(FVIII, FIX, VWF) or to 70 iu/dl (FXI) during labour and delivery
and to maintain this for at least 3 days after vaginal delivery or
at least 5 days after caesarean section
• Use regional anaesthesia only after careful evaluation and if
there is a normal factor level and coagulation screen
• Avoid invasive intrapartum fetal monitoring techniques and
traumatic instrumental deliveries if the fetus is at risk
• Obtain a cord blood sample for assessment of neonatal
coagulation status in neonates at risk of moderate to severe
inherited bleeding disorder
• Avoid intramuscular injections in neonates at risk until the
coagulation status is known: give oral vitamin K and
immunisation through the intradermal or subcutaneous
routes
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18 Kadir RA, Lee CA, Sabin CA, Pollard D, Economides DL. Pregnancy in
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19 Greer IA, Lowe GD, Walker JJ, Forbes CD. Haemorrhagic problems in
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21 Kujovich JL. von Willebrand disease and pregnancy. J Thromb Haemost
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22 Rick ME, Williams SB, Sacher RA, McKeown LP. Thrombocytopenia
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23 Plug I, Mauser-Bunschoten EP, Brocker-Vriends AH, van Amstel HK,
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24 United Kingdom Haemophilia Centre Doctors’ Organisation (UKHCDO).
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haemophilia and other hereditary bleeding disorders. Haemophilia
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27 Mannucci PM, Aberg M, Nilsson IM, Robertson B. Mechanism of
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31 Cunningham FG, MacDonald PC, Gant NF. Abnormalities of the third
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33