GUIDELINES FOR THERAPEUTIC ANTICOAGULATION IN

PREGNANCY

Key Words: therapeutic anticoagulation; dosage; management

Background

This guideline deals with pregnant women who are already on therapeutic
anticoagulation prior to pregnancy or who develop venous thromboembolism (VTE)
requiring therapeutic anticoagulation during pregnancy.

The guidelines are based on tinzaparin as the low molecular weight heparin (LMWH)
of choice as this is in current use for women presenting to the hospital with
thromboembolic disease. Note that no LMWH is licensed for use in pregnancy but
LMWH is as safe and efficacious as unfractionated heparin (also not licensed for use
in pregnancy). LMWHs are more effective than unfractionated heparin with a lower
mortality and fewer haemorrhagic complications in the initial treatment of DVT in non-
pregnant women. They are as effective as unfractionated heparin in the treatment of
pulmonary embolism. Like all anticoagulants, LMWH should be used with caution in
women with suspected bleeding disorders, thrombocytopaenia, liver and renal
disease.

Placental transfer

Warfarin crosses the placenta and may be associated with miscarriage, teratogenicity
and fetal intracranial haemorrhage. It should be avoided in the first trimester of
pregnancy and should not be used as delivery approaches. Heparin and LMWH do
not cross the placenta.

Breast milk transfer

Warfarin, heparin and LMWH are not detected in breast milk so there is no contra-
indication to breast feeding.

Therapeutic tinzaparin (please also refer to product literature)

Tinzaparin comes in fixed dose syringes and multi-dose vials. Only fixed-dose
syringes should be used for pregnant women. The concentration to use for
therapeutic tinzaparin is is 20 000iu/ml.

Women > 105kg (use pre-pregnancy or booking weight at approx. 16 weeks)

May need to use a combination of fixed dose syringes. The therapeutic dose is
usually given once daily but can be halved and given twice daily – adjust the syringes
accordingly

Dose
Use pre-pregnancy or booking weight at approximately 16 weeks, NOT the current
weight.
175 anti Xa UNITS per kg (the volume can be rounded to the nearest 0.05ml - use
the most appropriate syringe - see above)
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Dosage calculation

Injection volume (ml) = 7 x bodyweight (kg)

800

Syringe size weight (kg) injection vol prescribed dose

(tinzaparin) (ml) (anti Xa iu)
0.5ml 40 0.35 7000
45 0.40 7875
50 0.45 8750
55 0.50 9625
0.7ml 60 0.55 10500
65 0.55 11375
70 0.60 12250
75 0.65 13125
80 0.70 14000
0.9ml 85 0.75 14875
90 0.80 15750
95 0.85 16625
100 0.90 17500
105 0.90 18375
>105 combine doses
to reach weight
eg if 120kg use
2 x 60kg = 2 x
0.7ml syringes

Major side effects

Osteoporosis (up to 1%); thrombocytopenia; haemorrhage; hair loss; allergic

reactions

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Starting therapeutic tinzaparin

Women already on anticoagulation Suggested management

Previous VTE requiring long term Stop warfarin when pregnancy confirmed
anticoagulation/other thrombotic (there seems to be no teratogenic effect
condition requiring long term before 6 weeks); check platelets and
anticoagulation clotting screen; start therapeutic
tinzaparin according to pre-pregnancy/
booking weight; consider referral to
anticoagulant practitioners
Mechanical heart valves Discuss with consultant cardiologist
preferably before becoming pregnant
Women who start anticoagulation Suggested management
during pregnancy
Women who develop DVT/PE in current Check platelets and clotting screen; start
pregnancy therapeutic tinzaparin according to pre-
pregnancy/ booking weight; consider
referral to anticoagulant practitioners
Women who require anticoagulation for Check platelets and clotting screen; start
other reason e.g. atrial fibrillation/ therapeutic tinzaparin according to pre-
cerebral event occurring in pregnancy pregnancy booking weight; consider
referral to anticoagulant practitioners

Monitoring of therapeutic LMWH

LMWH is not usually monitored. LMWH does not affect the prothrombin time (PT) or
the INR; it can prolong the APTT in some women but the APTT is NOT useful for
monitoring. Anti Xa levels are not reliable and are not performed. Patients with
impaired renal function may accumulate LMWH – use with care.

Platelet counts

LMWH is much less likely to cause thrombocytopenia than unfractionated heparin.

Platelet counts should be checked prior to commencing treatment and 7 to 10 days
after commencing therapeutic heparin and monthly thereafter. They should also be
checked if unexpected bruising or bleeding occurs. LMWH rarely causes heparin-
induced thrombocytopenia/thrombosis (HIT).

Reversal of LMWH

Protamine reverses unfractionated heparin but only partially binds to LMWH.

A dose of 1mg protamine/100iu LMWH reverses 90% of anti lla and 60% of anti Xa
activity – the clinical effect of the residual anti Xa is not known. Both anti-lla and anti
Xa activity may return up to three hours after protamine reversal, possibly due to
release of additional LMWH from depot tissues.

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Duration of anticoagulation during pregnancy

• distal DVT: minimum of 12 weeks therapeutic anticoagulation

• proximal DVT or PE: minimum of 26 weeks therapeutic anticoagulation
• if this does not reach 38 weeks gestation ⇒ prophylactic anticoagulation to
delivery and for at least 6 weeks postpartum
• if this reaches delivery time ⇒ convert to prophylactic dose for delivery and
therapeutic dose for agreed total time ( 21 or 26 weeks).

Planning delivery on therapeutic tinzaparin

Labour
• Consider splitting therapeutic dose from daily to bd from 36 weeks to achieve
flexibility.
• Consider induction of labour at term to allow elective changes in dosing. If
suspicion of labour, or labour is established, no further therapeutic doses
should be given.
• The next dose should be 4500 units as prophylactic syringe. Regional
anaesthesia may be contraindicated for these women but each case should be
considered individually (refer to “Regional anaesthesia” below).

Patients with an increased risk of bleeding eg major haemorrhage, progressive

wound haematoma, suspected intra-abdominal bleeding, coagulopathy,who require
continued full dose anticoagulation may be better managed with iv heparin which has
a shorter half life.

Patients with mechanical heart valves - cardiological opinion is needed. If mother on

warfarin caesarean section should be considered to protect the fetus from haemorrhage.

• unless a patient has had a DVT or PE within 4 weeks prior to delivery OR has a
condition requiring therapeutic anticoagulation continuously eg mechanical heart
valve, the risks of bleeding at delivery should be reduced by switching the patient
to prophylactic heparin at time of delivery
• if suspicion of labour or labour is established, no further therapeutic doses should
be given
• Next dose should be a prophylactic dose of 4500 units tinzaparin in a fixed dose
prophylactic syringe
• Daily prophylactic doses should continue until delivered and haemostasis
achieved
• See post partum anticoagulation for continuation
• Some patients may require therapeutic anticoagulation throughout labour eg
mechanical heart valves or PE/DVT within 4 weeks; these patients need individual
management which should include discussion with consultant haematologist and
other appropriate staff eg consultant cardiologist. These patients may require iv
heparin throughout labour.

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Regional anaesthesia (see guideline CA2031)

• Regional anaesthesia is contra-indicated in women on therapeutic

anticoagulation unless 24 hours have elapsed since the last dose of tinzaparin
(whether once or twice daily dosing). It is contraindicated in women receiving iv
heparin unless it is safe to temporarily stop the infusion and the APTT becomes
normal (check 3h after stopping iv heparin).
• After a prophylactic dose regional anaesthesia should not be used for 12 hours.
• The next dose of tinzaparin should not be given until 4 hours after the epidural
catheter has been removed.

Post partum anticoagulation

• Recommence full dose therapeutic LMWH after delivery (bd or once daily dose if
no bleeding problems) and warfarinise.
• Women with increased risk of bleeding eg major haemorrhage, progressive
wound haematoma, suspected intra-abdominal bleeding, coagulopathy, who
require continued full dose anticoagulation may be better managed with iv heparin
which has a shorter half life until risk of bleeding reduced
• Target INR in most cases is 2.5 or 3.5 in some patients with mechanical heart
valves
• The duration of anticoagulation is dependent on the reason for anticoagulation
and other risk factors but is usually between 6 and 12 weeks post partum.
• Patients who sustain VTE in late pregnancy may need longer anticoagulation eg
PE at 26 weeks needs 14 weeks to term plus further 12 weeks of therapeutic
anticoagulation

Referral to anticoagulant nurse practitioners

The anticoagulant nurse practitioners (Bleep 0799) have taken over the anticoagulant
dosing of inpatients on the wards as well as receiving fast track outpatient DVT
referrals. There are special forms for both referrals, which are available on wards and
must be completed fully.

Referral to consultant haematologists

This should be done via usual hospital channels. The team is always happy to
discuss and advise on individual cases.

Acknowledgements:

The guideline was written in conjunction with Dr Gillian Turner, Consultant

Haematologist and Dr Debbie Browne, Consultant Anaesthetist.

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References:

Horlocker TT, Heit, JA: Low Molecular weight heparin: biochemistry, pharmacology,
perioperative prophylaxis regimes, and guidelines for regional anesthetic
management. Anesthesia and Analgesia 1997; 85: 874-85

www.rcog.org.uk: Thromboembolic disease in Obstetrics and Gynaecology: Acute

management February 2001

Thromboembolic disease in pregnancy and the puerperium: acute management April

2001. Greentop guideline number 28 Royal College of Obstetricians and
Gynaecologists

Greer I.A. Thrombosis in pregnancy.: Maternal and Fetal issues. Lancet 1999; 353:
1258-65.

ACOG Committee Opinion. Anticoagulation with LMWH during pregnancy.

International Journal of Obstetrics and Gynecology 1999; 65: 89-90.

McColl M.D., Walker I.D. and Greer I.A. The role of inherited thrombophilia in venous
thromboembolism associated with pregnancy. Brit J Obstet Gynaecol 1999; 106:
756-66.

RCW FdeB DIF KPS EPM FHH SM RS SAM

Approved by the Clinical Guidelines Assessment Panel 20 September 2006

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