Treatment of venous thromboembolism in pregnancy

Treatment of venous thromboembolism in pregnancy - technical

LMWH is the treatment of choice for venous thromboembolism in pregnancy in most cases. With massive pulmonary thromboembolism causing haemodynamic compromise there may be a place for management with intravenous UFH and thrombolysis. In women at risk of thrombosis and with concurrent high risk of haemorrhage, such as those with major antepartum haemorrhage, coagulopathy, progressive wound haematoma, suspected intra-abdominal bleeding, or postpartum haemorrhage, UFH is often preferred as it has a shorter half-life than LMWH and its activity is more completely reversed with protamine sulphate.

A large systematic review demonstrated a risk of recurrent venous thromboembolism of 1.15% when treatment doses of LMWH were used to manage venous thromboembolism in pregnancy, which compares favourably with recurrence rates of 5 to 8% reported in trials carried out in nonpregnant patients treated with LMWH or UFH followed by coumarin therapy who were followed up for 3 to 6 months.

In view of the increased renal excretion of dalteparin and enoxaparin during pregnancy, a twice daily dosage regimen for these LMWHs in the treatment of venous thromboembolism in pregnancy is currently recommended (enoxaparin 1 mg/kg twice daily; dalteparin 100 units/kg twice daily) for initial treatment (Table 1).

Table 1 Typical initial doses of LMWH used for treatment of acute venous thromboembolism in pregnancy.
Early pregnancy weight (kg) Initial dose of enoxaparin (mg, twice daily)
<50  40
50–69 kg  60
70–89 kg  80
≥90 kga 100

a In obese patients it is recommended that dose capping is not used.

Experience indicates that satisfactory anticoagulant effects are obtained using this weight-based regimen. Monitoring of anti-Xa to assess the effect of LMWH is not routinely required, particularly as there are concerns over the accuracy of such monitoring, but there is a case doing so at extremes of body weight or in the presence of renal impairment: the target therapeutic range is 0.5 to 1.2 units/ml for peak levels (around 3 h post injection). 

As warfarin is generally avoided for maintenance therapy in pregnancy, women with antenatal venous thromboembolism are usually managed with therapeutic subcutaneous LMWH for the remainder of the pregnancy. They should be taught to self-inject, appropriate arrangements should be made to allow safe disposal of needles and syringes, and they can then be managed as outpatients until delivery.

In order to avoid an unwanted anticoagulant effect during delivery, it is suggested that heparin be discontinued 24 h before elective induction of labour or caesarean section.

Anticoagulant therapy should be continued for at least 6 weeks postpartum, and longer if required to allow a total duration of treatment of 6 months. If the woman chooses to commence warfarin postpartum, this can usually be initiated on the third postnatal day. Switching from LMWH to warfarin can be associated with secondary postpartum haemmorrhage, hence warfarin administration should be delayed further in women with risk of postpartum haemmorrhage.

Massive pulmonary thromboembolism

Intravenous UFH remains the preferred treatment in massive pulmonary thromboembolism because of its rapid effect and extensive experience of its use in this situation. A loading dose of 5000 IU followed by continuous intravenous infusion of 1000 to 2000 IU/h adjusted by the activated partial thromboplastin time (APTT) (target APTT ratio usually 1.5–2.5) monitoring 6 h after the loading dose and then at least daily.

However, the APTT is unreliable in pregnancy and an apparent heparin resistance occurs due to the coagulation changes in pregnancy. Anti-Xa monitoring can be used in this situation (target 0.35–0.70 IU/ml—note that this is different for the target used with LMWH due to differences in action of UFH). Thrombolysis can be considered in severe cases.

Women receiving therapeutic-dose UFH should have their platelet count monitored (see above). Pregnant women who develop HIT and require ongoing anticoagulant therapy should be managed with the heparinoid danaparoid sodium, or possibly fondaparinux. Warfarin may also be justified in this situation.