In addition to these evidence-based recommendations, the guideline development group also identifies points of best clinical practice in the original guideline document.
Levels of evidence (Ia-IV) and grading of recommendations (A-C) are defined at the end of the "Major Recommendations" field.
Preconceptual Antenatal Risk Assessment
Risk Factors
C - All women should undergo an assessment of risk factors for venous thromboembolism (VTE) in early pregnancy or before pregnancy. This assessment should be repeated if the woman is admitted to hospital or develops other intercurrent problems.
See the table below for risk factors for venous thromboembolism in pregnancy and the puerperium.
| Risk factors for venous thromboembolism in pregnancy and the puerperium a |
| Pre-existing |
New onset or transientb |
- Previous VTE
- Thrombophilia
- Congenital
- Antithrombin deficiency
- Protein C deficiency
- Protein S deficiency
- Factor V Leiden
- Prothrombin gene variant
- Acquired (antiphospholipid syndrome)
- Lupus anticoagulant
- Anticardiolipin antibodies
- Age over 35 years
- Obesity (body mass index [BMI] >30 kg/m2) either pre-pregnancy or in early pregnancy
- Parity >4
- Gross varicose veins
- Paraplegia
- Sickle cell disease
- Inflammatory disorders (e.g., inflammatory bowel disease)
- Some medical disorders (e.g., nephrotic syndrome, certain cardiac diseases)
- Myeloproliferative disorders (e.g., essential thrombocythaemia, polycythaemia vera)
|
- Surgical procedure in pregnancy or puerperium (e.g., evacuation of retained products of conception, postpartum sterilisation)
- Hyperemesis
- Dehydration
- Ovarian hyperstimulation syndrome
- Severe infection (e.g., pyelonephritis)
- Immobility (>4 days bed rest)
- Pre-eclampsia
- Excessive blood loss
- Long-haul travel
- Prolonged labourc
- Midcavity instrumental deliveryc
- Immobility after deliveryc
|
a Although these are all accepted as thromboembolic risk factors, there are few data to support the degree of increased risk associated with many of them.
b These risk factors are potentially reversible and may develop at later stages in gestation than the initial risk assessment or may resolve; an ongoing individual risk assessment is important.
c Risk factors specific to postpartum VTE only
|
Investigation of Women with Previous VTE
B - Women with previous VTE should be screened for inherited and acquired thrombophilia ideally before pregnancy.
Thromboprophylaxis During Pregnancy and the Puerperium
Expert haematological advice or referral to a joint obstetric and haematology clinic should be sought in cases when the antenatal team is uncertain about thromboprophylaxis.
Women With a Previous VTE and No Thrombophilia
C - Women with previous VTE should be offered postpartum thromboprophylaxis with low molecular weight heparin (LMWH). It may be reasonable not to use antenatal thromboprophylaxis with heparin in women with a single previous VTE associated with a temporary risk factor that has now resolved.
C - Women with previous recurrent VTE or a previous VTE and a family history of VTE in a first-degree relative should be offered thromboprophylaxis with LMWH antenatally and for at least six weeks postpartum.
Women With a Previous VTE Who Have Inherited Thrombophilia
Expert haematological advice should be sought for women with symptomatic thrombophilia, as specific thrombophilias, particularly antithrombin (AT) deficiency, merit higher doses of LMWH (see Table 2 in the original guideline document) for thromboprophylaxis.
B - Women with previous VTE and thrombophilia should be offered thromboprophylaxis with LMWH antenatally and for at least six weeks postpartum.
Women With Inherited Thrombophilia Without Previous VTE
Women should be stratified according to the level of risk associated with their thrombophilia. Since the risk of VTE is lower in women with no history of VTE, antenatal thromboprophylaxis is not always necessary, except in those with combined defects, those homozygous for defects, or those with antithrombin deficiency. Women with antithrombin deficiency should always receive thromboprophylaxis in pregnancy and the puerperium.
Women with known inherited or acquired thrombophilia may qualify for LMWH or warfarin for six weeks following delivery, even if they were not receiving antenatal thromboprophylaxis if they have other risk factors (see table, above).
C - Women with asymptomatic inherited or acquired thrombophilia may qualify for antenatal or postnatal thromboprophylaxis, depending on the specific thrombophilia and the presence of other risk factors.
Women with Acquired Thrombophilia (Antiphospholipid Syndrome)
Women with antiphospholipid syndrome identified because of recurrent miscarriage may not require LMWH for six weeks postpartum but should receive LMWH for at least three to five days, especially if they have other risk factors.
Women Without Previous VTE or Thrombophilia
Clinical judgement is required with regard to the weighting of the above risk factors. There are circumstances where one or two risk factors alone may be sufficient to justify antenatal thromboprophylaxis with LMWH, for example, an extremely obese woman admitted to the antenatal ward.
The risk of VTE should be discussed with women at risk, and the reasons for individual recommendations explained.
Timing and Duration of Thromboprophylaxis
Antepartum
As VTE during pregnancy has an equal distribution throughout gestation, if a decision is made to initiate thromboprophylaxis antenatally, this should begin as early in pregnancy as practical. Once antenatal treatment is initiated, it should continue until delivery unless a specific risk factor is removed or disappears.
Women with ovarian hyperstimulation syndrome (OHSS) require thromboprophylaxis for at least the period of inpatient stay. Similarly, women with multiple risk factors for VTE and at risk of OHSS undergoing ovulation induction may also be considered for thromboprophylaxis. Advice for pregnant women travelling by air is available.
Postpartum
Postpartum thromboprophylaxis should be given as soon as possible after delivery, provided that there is no postpartum haemorrhage. Those with postpartum haemorrhage should be fitted with thromboembolic deterrent stockings. If the woman has been given regional analgesia, LMWH should be withheld until four hours after insertion or removal of the epidural catheter (or six hours if either insertion or removal were traumatic). The first postpartum dose can be given after insertion but before removal of the epidural catheter.
As the prothrombotic changes of pregnancy do not revert completely to normal until several weeks after delivery, postpartum thromboprophylaxis is normally continued for six weeks in high-risk women. In practice, this will mean women learning to inject themselves if they have not already commenced heparin antenatally. However, for women at lower risk, prophylaxis for three to five days is usually recommended, despite the lack of evidence in this area. Low risk includes those with two current or persisting risk factors as discussed in the table above and asymptomatic thrombophilias with low thrombotic risk (heterozygous factor V Leiden and prothrombin gene variant).The risk of VTE reduces when women are mobile postpartum but does not disappear. If the woman is discharged home early, her thromboprophylaxis should be continued at home, to complete the course of three to five days. The combined oral contraceptive pill should not be prescribed during the first three months postpartum for women with other risk factors for VTE.
Just as circumstances and risk factors can change antenatally so too may they in the puerperium. Therefore, puerperal women undergoing surgery for any reason or those who develop severe infection or who choose to travel long-haul are at increased risk of VTE even though they may have been discharged from hospital following vaginal delivery several weeks before.
B - Antenatal thromboprophylaxis should begin as early in pregnancy as practical. Postpartum prophylaxis should begin as soon as possible after delivery (but see precautions after use of regional anaesthesia).
Agents for Thromboprophylaxis
The different options for and types of treatment should be discussed with the mother.
Low Molecular Weight Heparin
B - Low molecular weight heparins are the agents of choice for antenatal thromboprophylaxis. They are as effective as and safer than unfractionated heparin in pregnancy.
See Table 2 of the original guideline document for suggested antenatal prophylactic and therapeutic doses of LMWH. Experience indicates that, provided that the woman has normal renal function, monitoring of anti-Xa levels is not required when LMWH is used for thromboprophylaxis. In antithrombin deficiency, anti-Xa monitoring is critical, higher doses of LMWH may be necessary, and these patients should be monitored by a haemostatic expert. Antithrombin concentrates may be required. Although the risk of heparin-induced thrombocytopenia is extremely low with LMWH and has never been reported in pregnancy, current guidelines still recommend checking the platelet count one week after starting LMWH.
Where antenatal thromboprophylaxis with LMWH is given to women who are normally on long-term oral anticoagulants, usually because of previous recurrent VTE and/or a thrombophilia, higher prophylactic doses or therapeutic doses of LMWH may be appropriate (see Table 2 of the original guideline document). Whether high prophylactic doses or therapeutic doses are required is controversial and there is some evidence from nonpregnant and pregnant data that the former may suffice. For postpartum thromboprophylaxis, LMWH is probably the agent of choice for women who had LMWH antenatally or for those requiring only three to five days of postpartum treatment. Experience of enoxaparin in the puerperium reports no adverse effects on the baby resulting from breastfeeding.
Low-Dose Aspirin
The use of low-dose aspirin (75 mg daily) may be appropriate in situations where the risk of VTE is increased but is not deemed high enough to warrant the use of antenatal LMWH; for example, in women with previous provoked VTE without thrombophilia. Women should be advised of the lack of evidence for benefit of aspirin use for thromboprophylaxis in pregnancy.
Warfarin
Warfarin is safe after delivery and for breastfeeding, although it requires close monitoring, frequent visits to an anticoagulant clinic, and carries an increased risk of postpartum haemorrhage and perineal haematoma compared with LMWH. It is not appropriate for women requiring only three to five days of postpartum prophylaxis.
If the woman chooses to commence warfarin postpartum, this can usually be initiated on the second or third postnatal day. LMWH should be continued until the international normalised ratio is greater than 2.0.The dosage regimens are the same as for women converting to warfarin postpartum following an acute VTE in pregnancy.
B - Warfarin should usually be avoided during pregnancy. It is safe after delivery and during breastfeeding.
Dextran
Dextran should not be used primarily because of the risk of anaphylaxis, which has killed fetuses by causing massive histamine release and uterine hypertonus.
Graduated Elastic Compression Stockings
Graduated elastic compression stockings may be used antenatally.
Class-I thromboelastic stockings are appropriate for hospital inpatients at increased risk of VTE and may be combined with LMWH. Their use is also recommended for pregnant women travelling by air.
Definitions:
Grading of Recommendations
Grade A - Requires at least one randomised controlled trial as part of a body of literature of overall good quality and consistency addressing the specific recommendation (evidence levels Ia, Ib)
Grade B - Requires the availability of well-conducted clinical studies but no randomised clinical trials on the topic of recommendations (evidence levels IIa, IIb, III)
Grade C - Requires evidence obtained from expert committee reports or opinions and/or clinical experience of respected authorities. Indicates an absence of directly applicable clinical studies of good quality (evidence level IV)
Levels of Evidence
Ia: Evidence obtained from meta-analysis of randomised controlled trials
Ib: Evidence obtained from at least one randomised controlled trial
IIa: Evidence obtained from at least one well-designed controlled study without randomisation
IIb: Evidence obtained from at least one other type of well-designed quasi-experimental study
III: Evidence obtained from well-designed non-experimental descriptive studies, such as comparative studies, correlation studies, and case studies
IV: Evidence obtained from expert committee reports or opinions and/or clinical experience of respected authorities
