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Position Statement
Anticoagulation in pregnancy and the puerperium
A Working Group on behalf of the Obstetric Medicine Group of
Australasia
MJA 2001; 175: 258-263
Abstract -
Management and prophylaxis of venous thromboembolism in pregnancy and the puerperium -
Acute venous thromboembolism -
Prophylaxis of venous thromboembolism -
General -
Previous thromboembolism -
Previous single VTE and no recognised thrombophilia -
Previous recurrent VTE or idiopathic VTE -
Familial thrombophilia -
Hyperhomocysteinaemia -
Antiphospholipid syndrome and VTE -
Management and prophylaxis of obstetric problems associated with uteroplacental thrombosis -
References -
Authors' details
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More articles on Obstetrics & gynaecology and women's health
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- For the management of acute thrombotic events in pregnancy
therapeutic doses of low molecular weight heparins (LMWH) may be
used, unless the shorter half-life of intravenous unfractionated
heparin (UH) and predictable reversibility by protamine are
important. Treatment should be continued up until delivery and into
the puerperium.
- Pregnant women who have had an acute thrombotic event should be
delivered by a specialist team.
- In the case of recent thrombosis, delivery should be planned and the
time during which anticoagulation therapy is ceased around the time
of delivery should be minimised.
- Therapeutic doses of LMWH contraindicate the use of regional
anaesthesia, and a switch to intravenous UH before delivery may allow
greater flexibility in this regard.
- Prophylactic doses of LMWH can be used to reduce the risk of recurrent
thromboembolic events in pregnancy. The regimen used will depend on
the previous history, the family history and the presence of risk
factors, including the genetic and acquired causes of
thrombophilia.
- Women with mechanical heart valves are at high risk during pregnancy
and require therapeutic anticoagulation throughout pregnancy
under the direction of experienced specialists.
- Low-dose aspirin can reduce the risk of recurrent pre-eclampsia by
about 15%, but the role of UH and LMWH in the prevention of recurrent
miscarriage or obstetric complications associated with
uteroplacental insufficiency is still uncertain.
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Low molecular weight heparins (LMWH) are being used increasingly as
standard treatment for venous thrombosis, replacing
unfractionated heparin (UH) for both therapeutic and prophylactic
anticoagulation. Compared with UH, LMWH have increased
bioavailability and a longer half-life. They also have the benefits
of ease of administration, often as a single daily dose, have reduced
requirements for monitoring, and are associated with less
heparin-induced thrombocytopenia, reduced bleeding
complications and improved patient acceptability.1 Heparins do not cross the placenta, whereas warfarin
does.2,3 By contrast, warfarin is
teratogenic between six and 12 weeks' gestation, and may cause fetal
and neonatal bleeding if used during the second or third trimester.
Except perhaps in women with mechanical heart valves, there is
general agreement that UH or LMWH should be substituted for warfarin
as soon as pregnancy is diagnosed.
Long-term treatment with UH carries risks of maternal
osteoporosis4-6 and heparin-induced
thrombocytopenia. Consistent, long term therapeutic
anticoagulation can be hard to achieve with subcutaneous UH, because
of low bioavailability and the changing anticoagulant response to UH
as pregnancy progresses, often requiring close laboratory
monitoring. LMWH require much less monitoring and appear to carry a
smaller risk of heparin-induced thrombocytopenia, bleeding, and
probably osteoporosis.7-9
Data on the effectiveness and safety of LMWH in pregnancy are limited
but systematic reviews are becoming available.10 Given the
convenience of LMWH and doctors' increasing familiarity with their
use, there is growing opinion that LMWH have a role in pregnancy in
preference to UH. In this position paper we summarise current views
and make consensus recommendations for anticoagulation in
pregnancy and the puerperium. The consensus process followed for
this article is summarised in Box 1.
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Acute venous thromboembolism | |
Antenatal management: Clinical trials in non-pregnant patients
show that LMWH are at least as effective and safe as UH in the initial
management of acute proximal or calf deep venous thrombosis
(DVT).1 Recurrence of
thromboembolism is reduced by ongoing warfarin therapy and, in the
case of proximal DVT, treatment should be continued for at least six
months (C1). The standard initial treatment for
pulmonary embolism, whether during pregnancy or not, remains
intravenous UH (C2).
For an antenatal DVT, treatment should start with a LMWH at the
therapeutic dose recommended by the manufacturers9(Box 2)
(C1). Intravenous UH may be preferred in situations
where its short half-life and predictable reversibility by
protamine sulfate are important (eg, when delivery or surgery may be
imminent). Calf DVT should be treated in the same way as proximal DVT in
pregnancy because of ongoing hypercoagulability during pregnancy
(C2). If intravenous UH is used for the initial treatment
of pulmonary embolism, therapeutic doses of LMWH may be commenced
once the patient is haemodynamically stable (C1).
Anticoagulation therapy should then be maintained until delivery
(C1). It is generally recommended that therapeutic
doses of UH or LMWH be continued throughout pregnancy.9,11,12 In
practice, some clinicians change to a prophylactic dose of LMWH after
12 weeks of therapy if the woman is still pregnant, and continue with
this dose until labour (Box 2) (C3). The rationale for
this approach includes a declining risk of recurrence with time after
acute venous thromboembolism (VTE),13 a desire to reduce
osteoporosis associated with LMWH, and the suggestion from small
trials in non-pregnant patients that lower prophylactic or
intermediate doses of LMWH may be as effective as warfarin in
preventing secondary recurrence of VTE.14-16 The safety of such a
reduction of LMWH dose before 12 weeks after acute VTE in pregnancy
needs to be established in clinical trials.
Monitoring: There is no need to use an anti-factor Xa assay to monitor
either therapeutic or prophylactic doses of LMWH (C2).
Therapy with UH can be monitored and managed according to the
activated partial thromboplastin time (APTT).
Management of labour and delivery: Women requiring therapeutic
anticoagulation should be counselled before delivery, which should
be planned under the care of a specialist team (C1).
Elective delivery allows for dose adjustment to minimise the
opposing risks of bleeding at delivery and of further
thrombosis.13 Vaginal delivery is
preferable, as there is less risk of haemorrhage than with caesarean
section. Delivery by caesarean section should be determined on the
basis of obstetric indications (C1). The use of regional
anaesthesia requires special consideration, and is outlined in Box
3.
The intensity of anticoagulation therapy required during delivery
depends on how recently the VTE occurred. If within the last month,
each day without anticoagulation therapy is associated with a 1%
absolute increase in the risk of recurrence.13 It is therefore important
to minimise the time off anticoagulation. Intravenous UH should be
substituted for LMWH 24-36 hours before obstetric intervention,
aiming to maintain the APTT at 1.5-2 times baseline. After induction,
UH therapy is ceased once labour is established, allowing the APTT to
return to normal, usually within 4-6 hours. Women requiring elective
caesarean section should cease UH therapy six hours before surgery to
allow for the full range of obstetric and anaesthetic options
(C1).
If the VTE occurred between one and three months previously,
therapeutic LMWH can be reduced to a prophylactic dose for 24-48 hours
and labour can then be induced. The last dose of LMWH is given the night
before induction. In women whose cervical assessment suggests that
labour is likely to be established within a few hours of induction, the
last dose of LMWH before induction may be withheld (C2).
Women who have had a VTE more than three months previously and who are
still receiving a therapeutic dose of LMWH can be switched to a
prophylactic dose at 38 weeks' gestation, allowing spontaneous
labour to occur. Again, LMWH are withheld at the onset of labour
(C2). Alternatively, if a woman wishes to be assured of
access to epidural anaesthesia, induction of labour can be offered,
with the last dose of LMWH on the day before the day of induction
(C2).
Anti-embolism stockings, compression devices and electrical calf
stimulators may be used and continued postpartum, especially if
caesarean delivery is undertaken (C1).
In all women in whom anticoagulants have been used, the third stage of
labour should be managed actively with oxytocic therapy and
controlled cord traction to minimise the risk of postpartum
haemorrhage (C1).
Postpartum management: Postpartum, anticoagulation therapy is
usually recommenced at the same intensity as that used antenatally.
Prophylactic doses can be recommenced within 2-6 hours of both
vaginal and caesarean deliveries (C1). This may be
prophylactic doses of LMWH or low-dose (12 000 U/24 h) UH infusion, if
rapid reversal of anticoagulation may be required.
Therapeutic doses of UH or LMWH may be reintroduced 24 hours after
vaginal delivery (C2). Caution should be exercised in
recommencing therapeutic doses of LMWH earlier than 24 hours after
operative delivery because of the risk of surgical bleeding, but most
women can be receiving therapeutic doses by 36-48 hours after
caesarean section (C1). Warfarin therapy can then be
initiated and, once therapeutic levels have been achieved,
continued in place of LMWH to complete the six months of therapy and for
at least six weeks postpartum. Neither medication contraindicates
breastfeeding (C1).
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General |
VTE remains a major cause of maternal mortality in Australia, the
United Kingdom and in the United States, occurring at a rate of
approximately one death per 100 000 maternities.11,12,18 The
rate is much higher in older women; in the UK, women aged over 39 years
had a mortality rate of 1 per 3300 pregnancies.19 VTE can occur at any time
during pregnancy; its prevalence is approximately equally
distributed between the three trimesters.20 Although two-thirds of
events occur antenatally, the day-by-day risk is greatest in the
first weeks after delivery.20 Major known risk factors for VTE in pregnancy and postpartum include
caesarean section (particularly in labour), obesity, prolonged bed
rest and immobility, pre-eclampsia, nephrotic syndrome, current
infection and other recent surgery, in addition to previous VTE and
thrombophilia. These risk factors often coexist and reinforce each
other. A risk-assessment profile may be constructed, as suggested in
the consensus report from the Royal College of Obstetricians and
Gynaecologists,21 which recommends
that:
- all "at risk" women should be monitored for
symptoms and signs of VTE during the first week postpartum;
- hydration should be maintained and early mobilisation encouraged;
- graduated compression stockings with or without calf stimulation
should be used during and after caesarean section in women at moderate
risk (one or two risk factors);
- in women at high risk (three or more risk factors), LMWH or UH
prophylaxis should be used and continued for at least five days.
The efficacy or benefit of these interventions is unknown, as no high
grade evidence is available.
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Previous thromboembolism | |
In women who have had previous VTE, the risk of recurrence will be
influenced by a number of factors, including whether the index event
was spontaneous or provoked, the presence or absence of a family
history of VTE, the presence of a known thrombophilia, or whether
there has been more than one episode of VTE. The decision as to whether
VTE prophylaxis is required throughout pregnancy or only postpartum
may be based on this information (Box 4).22 Women requiring prophylaxis during pregnancy can be managed with
low-dose LMWH (Box 2). They can then be allowed to come into
spontaneous labour (C2). LMWH are withheld at the onset
of labour (C2). Alternatively, if such a woman wishes to
be assured of access to regional anaesthesia, induction of labour can
be offered, with the last dose of LMWH on the day before the day of
induction (Box 3) (C2).
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Previous single VTE and no recognised thrombophilia | |
Both earlier and more recent cohort data suggest that most pregnant
women with a past history of a single precipitated thrombotic event in
or out of pregnancy, or associated with the combined oral
contraceptive pill, and who have no underlying thrombophilia, can be
safely managed by careful observation before delivery and
postpartum thromboprophylaxis for six weeks23 (C2).
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Previous recurrent VTE or idiopathic VTE | |
Women who have either recurrent VTE, previous idiopathic VTE, or a
previous VTE and a strong family history of VTE but with no
demonstrated cause for thrombophilia, may be given
thromboprophylaxis throughout pregnancy and for six weeks
postpartum23,24 (C1).
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Thromboembolism is a multifactorial disease, in many cases
developing as a result of a thrombotic tendency (a thrombophilia)
interacting with other factors, such as pregnancy.25,26
Situations in which such a thrombophilia may require consideration
during pregnancy are:
- previous personal thromboembolic disease
and known thrombophilia;
- no previous VTE, but a strong family history (ie, one or more
first-degree relatives affected) and known thrombophilia;
- no previous VTE, strong family history, no previous
investigations;
- no previous VTE, weak family history (ie, incidental finding of
thrombophilia in a family member); and
- no personal or family history of VTE, but known thrombophilia
detected after screening (eg, after obstetric complications or
before starting to take the combined oral contraceptive pill).
The known causes of familial thromboembolism differ in their risk of
associated thrombosis.27 The prevalence of such
thrombophilic disorders varies between populations.28 A combination
of any two or more inherited factors substantially increases the risk
of thromboembolism. Box 4 summarises the risk profiles of the various
genetic thrombophilias and offers guidelines for therapy. Box 5
describes management during pregnancy of medical problems
requiring anticoagulation outside pregnancy.
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In women with a previous history of VTE and hyperhomocysteinaemia, it
may be prudent to reduce plasma homocysteine concentrations by
folate supplementation throughout pregnancy, in addition to other
thromboprophylaxis (C2).
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The presence of a lupus anticoagulant or of moderately to strongly
positive titres of anticardiolipin antibody (ACA) is a strong risk
factor for recurrent VTE, especially in pregnancy. Suggestions for
treatment are shown in Box 4. Unless there is an associated history of
poor obstetric outcome (see below), low-dose aspirin therapy need
not be added (C2). On the other hand, it is contentious
whether women with a positive lupus anticoagulant with or without ACA
with no previous history of VTE (eg, women with systemic lupus
erythematosus) require any prophylactic treatment at all during
pregnancy. Low-dose aspirin may be a reasonable option for such women
(C1).
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A common pathophysiological link between various poor pregnancy
outcomes, including recurrent miscarriage, stillbirth, placental
abruption, fetal growth restriction and pre-eclampsia, is
thrombosis in the uteroplacental circulation. Antiplatelet agents
(especially low-dose aspirin) have been trialled, particularly for
preventing pre-eclampsia. A recent systematic review has shown a 15%
reduction in the incidence of recurrent pre-eclampsia when low-dose
aspirin is used, less benefit for the prevention of preterm birth and
no benefit for the prevention of fetal growth
restriction.35 Whether LMWH or UH can be
used safely and more effectively than just aspirin in placental
vasculopathy, with or without thrombophilia, is currently under
investigation. Only in the case of recurrent miscarriage associated
with the antiphospholipid syndrome has the addition of UH to aspirin
been shown to be beneficial.36 A number of small cohort
studies in women with previous obstetric complications who were
treated with LMWH showed a good outcome, but whether the outcome was
related to the use of LMWH is uncertain.37,38 While awaiting the results of further studies, and given the small
numbers of affected women, no specific treatment recommendations
can be made. We encourage clinicians to refer such patients to centres
where randomised controlled trials are being carried out or where
cohort studies are under way.
Competing interests: The authors are grateful to Pharmacia
Upjohn for an unrestricted financial grant towards the costs
involved in the preparation of this article, although the company did
not contribute in any way either to the analysis or to the
recommendations. There are no other known conflicts of
interest.
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Future research questions
The working party identified further areas for research.
These include: - Comparison of LMWH versus intravenous UH in acute DVT and pulmonary embolism in pregnancy.
- High-dose versus low-dose LMWH therapy for secondary prophylaxis after acute DVT in pregnancy.
- The value of prospective blinded anti-Xa levels in the use of therapeutic LMWH in pregnancy.
- The timing, benefits and risks of any dose adjustment of LMWH/UH, particularly peripartum.
- Controlled longitudinal studies of bone density and fracture rates in women using long-term LMWH.
- Prevention of pregnancy-associated VTE: the risks and benefits of LMWH thromboprophylaxis during pregnancy and postpartum for specific groups.
- Prevention of adverse pregnancy complications related to placental insufficiency.
- Randomised studies to determine the efficacy of LMWH in improving subsequent pregnancy outcome in women with specific pregnancy complications and an underlying thrombophilia.
- A register of women being treated with anticoagulants during pregnancy.
- A register to determine the clinical significance of thrombophilias in particular patient groups.
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Dahlman TC, Sjoberg HE, Ringertz H. Bone mineral density during
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Douketis JD, Ginsberg JS, Burrows RF, et al. The effects of
long-term heparin therapy during pregnancy on bone density — a
prospective matched cohort study. Thromb Haemost 1996; 75:
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Barbour LA, Kick SD, Steiner JF, et al. A prospective study of
heparin-induced osteoporosis in pregnancy using bone
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Nelson-Piercy C. Heparin-induced osteoporosis in pregnancy.
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Farquharson RG. Heparin, osteoporosis and pregnancy. Br J Hosp
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Ginsberg J, Greer I, Hirsh J. Use of antithrombotic agents during
pregnancy. Chest 2001; 199: 122S-131S.
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Sanson BJ, Lensing AW, Prins MH, et al. Safety of low molecular
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Greer IA. Thrombosis in pregnancy: maternal and fetal issues.
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Toglia M, Weg J. Current concepts: venous thromboembolism during
pregnancy. N Engl J Med 1996; 335: 108-114.
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Kearon C, Hirsh J. Management of anticoagulation before and after
elective surgery. N Engl J Med 1997; 336: 1506-1511.
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Pini M, Aiello S, Manotti C, et al. Low molecular weight heparin
versus warfarin in the prevention of recurrences after deep vein
thrombosis. Thromb Haemost 1994; 72: 191-197.
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Gonzalez-Fajardo J, Arreba E, Castrodeza J, Perez J, et al.
Venographic comparison of subcutaneous low-molecular weight
heparin with oral anticoagulant therapy in the long-term treatment
of deep venous thrombosis. J Vasc Surg 1999; 30: 283-292.
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Das S, Cohen A, Edmonson R, et al. Low molecular weight heparin
versus warfarin for prevention of recurrent venous
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Tryba M. European practice guidelines: thromboembolism
prophylaxis and regional anesthesia. Regional Anesthes Pain
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Maternal mortality committee. Maternal deaths in Australia
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Department of Health. Why mothers die. Report on confidential
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Ray JG, Chan WS. Deep vein thrombosis during pregnancy and the
puerperium: a meta-analysis of the period of risk and the leg of
presentation. Obstet Gynecol Surv 1999; 54: 265-271.
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Royal College of Obstetricians and Gynaecologists. Report of the
RCOG Working Party on prophylaxis against thromboembolism in
gynaecology and obstetrics. London: RCOG, 1995.
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McColl MD, Walker ID, Greer IA. The role of inherited
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Brill-Edwards P, Ginsberg J, Gent M, et al. Safety of withholding
antepartum heparin in women with a previous episode of venous
thromboembolism. N Engl J Med 2000; 343: 1439-1444.
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Letsky EA. Peripartum prophylaxis of thrombo-embolism.
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Rosendaal FR. Venous thrombosis: a multicausal disease.
Lancet 1999; 353: 1167-1173.
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Preston FE, Rosendaal FR, Walker ID, et al. Increased fetal loss in
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Gerhardt A, Scharf RE, Beckmann MW, et al. Prothrombin and factor V
mutations in women with a history of thrombosis during pregnancy and
the puerperium. N Engl J Med 2000; 342: 374-380.
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Seligsohn U, Lubetsky A. Genetic susceptibility to venous
thrombosis. N Engl J Med 2001; 344: 1222-1231.
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Chan WS, Anand S, Ginsberg JS. Anticoagulation of pregnant women
with mechanical heart valves — a systematic review of the
literature. Arch Intern Med 2000; 160: 191-196.
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Arnaout M, Kazma H, Khalil A, et al. Is there a safe anticoagulation
protocol for pregnant women with prosthetic valves? Clin Exp
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Elkayam U. Pregnancy through a prosthetic heart valve. J Am
Coll Cardiol 1999; 33: 1642-1645.
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Lee LH, Liauw PCY, Ng ASH. Low molecular weight heparin for
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Sadler L, McCowan L, White H, et al. Pregnancy outcomes and cardiac
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Rowan J, McCowan L, Raudkivi P, North R. Enoxaparin treatment in
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Knight M, Duley L, Henderson Smart DJ, King JF. Antiplatelet
agents for preventing and treating pre-eclampsia. Cochrane
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Rai R, Cohen H, Dave M, Regan L. Randomised controlled trial of
aspirin and aspirin plus heparin in pregnant women with recurrent
miscarriage associated with phospholipid antibodies (or
antiphospholipid antibodies). BMJ 1997; 314: 253-257.
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Brenner B, Hoffman R, Blumenfeld Z, et al. Gestational outcome in
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Riyazi N, Leeda M, de Vries J, et al . Low-molecular-weight heparin
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The authors of the Position Statement are listed below
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Department of Obstetrics, University of Adelaide, Women's and
Children's Hospital, North Adelaide, SA.
William M Hague, FRCP, FRCOG, Senior Physician in Obstetric
Medicine and Clinical Senior Lecturer.
National Women's Hospital, Auckland, New Zealand
Robyn A North, PhD, FRACP, Associate Professor in Obstetric
Medicine.
Flinders Medical Centre, Bedford Park, SA.
Alexander S Gallus, FRCPA, FRACP, Haematologist and
Professor.
King Edward Memorial Hospital, Subiaco, WA.
Barry N J Walters, MB BS, FRACP, Physician in Obstetric
Medicine and Clinical Associate Professor, Department of
Obstetrics and Gynaecology, University of Western Australia.
Christopher Orlikowski, MB BS, FANZCA, Anaesthetist.
Monash University, Monash Medical Centre, Melbourne, VIC.
Robert F Burrows, FACOG, FRANZCOG, Professor of
Maternal-Fetal Medicine.
Mater Mothers' Hospital, South Brisbane, QLD
Robert B Cincotta, FRANZCOG, CMFM, Specialist in
Maternal-Fetal Medicine.
North Western Adelaide Health
Service, Adelaide, SA.
Gustaaf A Dekker, PhD, FRANZCOG, Professor of Obstetrics and
Gynaecology.
Mercy Hospital for Women, East Melbourne, VIC.
John R Higgins, MD, FRANZCOG, Senior Lecturer in Obstetrics
and Gynaecology (currently, Professor of Obstetrics and
Gynaecology, University College, Cork, Ireland).
Royal Hospital for Women, Sydney, NSW.
Sandra A Lowe, MD, FRACP, Physician in Obstetric Medicine.
Royal North Shore Hospital, Sydney, NSW.
Jonathan M Morris, MD, FRANZCOG, Senior Lecturer in
Obstetrics and Gynaecology.
Nepean Hospital, Sydney, NSW.
Michael J Peek, PhD, FRANZCOG, Professor of Obstetrics and
Gynaecology.
Reprints will not be available from the authors.
Correspondence: Dr W
M Hague, Department of Obstetrics, Women's and Children's Hospital,
North Adelaide, SA 5006.
bill.hagueATadelaide.edu.au
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1: Consensus process
The authors of this position statement are members of the Obstetric Medicine Group of Australasia (OMGA), with a particular clinical and research interest in managing pregnant women with thromboembolic problems. The authors were all members of the working party, and include six obstetricians, four obstetric physicians, an obstetric anaesthetist and a clinical haematologist. We met collectively in October 1999 to discuss the broad issues of the use of low molecular weight heparins in pregnancy before producing a draft document; this was subsequently modified by written comments and refined at teleconferences in May, June and September 2000. The position statement is a consensus statement inasmuch as there is little high-grade evidence from either randomised trials or other cohort studies on which to make recommendations, especially for management. Our recommendations have been annotated to reflect the degree of agreement among us as follows:
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| 2: Doses of low molecular weight heparins |
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| Low molecular |
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| weight heparin |
Therapeutic dose |
Prophylactic dose |
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| Dalteparin (Fragmin) |
100U/kg twice daily |
5000U daily |
| Enoxaparin (Clexane) |
1 mg/kg twice daily |
40mg daily |
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or 1.5mg/kg daily |
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3: Suggested guidelines for regional anaesthesia and levels of consensus (Box 1)
- Regional anaesthesia (epidural or spinal block) is contraindicated during anticoagulation therapy because of the increased (although unquantified) risks of spinal haematoma17 (C1).
- If a regional anaesthetic is desired in women who require anticoagulation therapy, an elective delivery will allow for a planned reduction in dose or a change to intravenous unfractionated heparin (UH) (C1).
- Therapeutic subcutaneous injections of low molecular weight heparins (LMWH) or UH should be ceased at least 24 hours, and preferably 36 hours, before regional anaesthesia (epidural or spinal block) (C1).
- Intravenous UH (used to permit a rapid return of the APTT to normal after cessation of the infusion) should be discontinued at least six hours, and preferably 12 hours, before regional anaesthesia (C1).
- In women receiving prophylactic LMWH, an interval of more than 20 hours from the last dose should allow the placement of a regional block with minimal risk of complications (C2).
- A normal activated partial thromboplastin time (APTT) does not ensure minimal anticoagulant effect of LMWH, and the platelet count should be determined to exclude heparin-induced thrombocytopenia (C2).
- If caesarean section is being undertaken, further doses of LMWH should be delayed for at least four hours after placement of an uncomplicated regional block, and longer if the regional block has been complicated (C1).
- Low-dose LMWH therapy can be continued after delivery if there have been no complications in the siting of the regional block.17
- An epidural catheter can be removed 12-20 hours after a prophylactic dose of LMWH, and the next injection should be delayed by at least four hours after removal (C1).
- Women should be closely monitored postpartum for any symptoms or signs of spinal haematoma, in particular for numbness and weakness in the lower limbs, severe back pain, and bladder or bowel incontinence (C1).
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Box 4 consists of 4a, 4b, 4c, 4d.
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| 4a: Suggested management
guidelines and levels of consensus (see Box 1) |
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| Thromboprophylaxis against recurrent
venous thromboembolism (VTE) in pregnant women with previous VTE and no
identified thrombophilia, according to estimated pregnancy-related risk
of thrombosis |
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Single episode of VTE |
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| Thrombosis history |
Recurrent VTE |
Spontaneous |
Probable cause* |
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| Family history of VTE in one or more 1st degree relatives
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PrA (option ThA) (C2) |
PrA (C2) |
Negot (C2) |
| No family history of VTE |
PrA (C1) |
Negot (C2) |
Nil (C2) |
|
| *Risk factors present such as surgery, combined
oral contraceptive pill. |
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| 4b: Anticoagulation to prevent venous thromboembolism
(VTE) in pregnant women testing positive for lupus anticoagulant or anticardiolipin
antibodies (ACA), according to estimated pregnancy-related risk of thrombosis |
|
|
|
|
Lupus anticoagulant |
|
|
and/or ACA IgG |
ACA IgG weak |
|
moderate-strong |
positive,* ACA |
| Thrombosis history |
positive* |
IgM positive |
|
| Recurrent VTE in pregnancy despite prophylaxis |
ThA (C1) |
ThA (C1) |
| Recurrent VTE outside pregnancy |
ThA (C2) |
ThA (C2) |
| Previous VTE |
PrA (C1) |
Negot (C1) |
| No previous VTE |
Nil (C1) |
Nil (C1) |
|
| *Based on the highest-ever titre measured
in the individual patient. |
|
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| 4c: Preventing venous
thromboembolism (VTE) in pregnant women with established thrombophilias,
according to estimated pregnancy-related risk of thrombosis |
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
| Thrombosis history |
Antithrombin deficiency
(Very rare) |
Protein C deficiency
(Rare) |
Protein S deficiency
(Rare) |
FVL* or PGM
homozygous
(Uncommon) |
FVL* or PGM
heterozygous
(Common) |
|
| Personal history of VTE independent of family history |
ThA (C2) |
PrA (C1) |
PrA (C1) |
PrA (C1) |
Negot (C1) |
| |
|
|
|
|
|
| Family history of VTE in one or more 1st degree relatives
|
ThA/PrA (C3) |
PrA (C1) |
PrA (C1) |
PrA (C1) |
Negot (C1) |
| |
|
|
|
|
|
| Family history of VTE in a distant relative |
ThA/PrA (C3) |
PrA (C1) |
Negot (C1) |
Negot (C1) |
Nil (C1) |
| |
|
|
|
|
|
| No personal or family history of VTE |
ThA/PrA (C3) |
PrA (C1) |
Nil (C1) |
Nil (C1) |
Nil (C1) |
|
| *G1691A mutation in the factor V gene [Factor
V Leiden] causing activated protein C resistance; G20210A mutation in the
prothrombin (factor II) gene. |
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| 4d: Key to management recommendations |
|
|
| ThA |
Therapeutic anticoagulation necessary throughout pregnancy
and postpartum - very high risk (>20%). |
| |
|
| PrA |
Prophylaxis necessary throughout pregnancy and puerperium
- high risk (10%-20%). |
| |
|
| Negot |
Need for prophylaxis negotiable on a case-by-case basis
until further data become available - moderate risk (3%-10%). |
| |
|
| Nil |
Postpartum prophylaxis or no prophylaxis - low risk (3%). |
|
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5: Management during pregnancy of medical problems requiring anticoagulation therapy outside pregnancy (consensus levels are described in
Box 1)
- Women with mechanical heart valves require therapeutic doses of anticoagulant medication throughout pregnancy to prevent valve thrombosis or maternal thromboembolic events9 (C1).
- Women with mechanical heart valves should be managed under joint subspecialty care (C1).
- The maternal benefits of warfarin (prevention of valve occlusion and systemic embolism) must be balanced against hazards to the fetus (congenital anomalies, intracranial haemorrhage and fetal loss).29
- Unfractionated heparin (UH) and low molecular weight heparins (LMWH) are safe for the fetus, but there is still debate as to their therapeutic efficacy in the mother compared with that of warfarin.29-33
- UH is associated with higher rates of maternal thromboembolic complications, including fatal events.29,33
- There are limited data on the efficacy of LMWH in mechanical valves during pregnancy, but valve thrombosis may occur.34
- High rates of maternal valve thrombosis occur if subtherapeutic doses of UH or LMWH are used.9,30
- Women should participate in the choice of anticoagulation therapy (C2).
- In women with other diseases (eg, dilated cardiomyopathy) who require anticoagulation therapy to prevent thromboembolic complications, the use of therapeutic or prophylactic doses of LMWH will depend on the perceived
risk of thromboembolism (C1).
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