After an initial fall in the number of maternal deaths caused by thrombotic disease following the issuance of national guidelines on thromboprophylaxis in pregnancy and the puerper- ium in 2004, thrombosis and thromboembolism feature again in recent Confidential Enquiries into Maternal Deaths (CEMD) reports as the leading cause of direct maternal deaths during pregnancy and in the first 6 weeks postpartum. There has been no significant change in mortality due to venous thromboembolism (VTE) since 2009. The condition is associated with a high morbidity and mortality rate; the latter is around 15% with untreated calf vein thrombosis and is even higher with iliofemoral thrombosis, which is more common in pregnancy. Untreated pulmonary embolus (PE) in pregnancy may recur and is associated with a mortality of 25%.
Problems and special considerations
Physiological changes in pregnancy favour coagulation, making pregnant women far more likely to develop VTE than non-pregnant women. In addition, obesity and the gravid uterus may cause venous stasis while lying down and encourage thrombus formation. Other risk factors include bed rest, dehydration, coincident thrombophilia, pre-eclampsia, greater maternal age, higher parity, patient/family history, smoking, and caesarean section (the last by up to eight times).
Diagnosis of deep-vein thrombosis (DVT) in pregnancy may be difficult; however, a high index of suspicion is required since mortality audits have identified patients with classic symptoms and signs who were not treated effectively. Not only is the diagnosis often not considered in pregnancy, but women may be denied appropriate investigation because of their pregnant state.
Management options
Treatment of thromboembolism in pregnancy
Suspected DVT in pregnancy should be investigated with duplex ultrasonography and venography if necessary. A raised concentration of D-dimers or other fibrin degradation products may not be helpful, as both may be raised in normal pregnancy; however, low levels make the diagnosis unlikely. Suspected PE in pregnancy should be investigated with chest radiography, arterial blood gas analysis and electrocardiography, followed by a ventilation-perfusion scan or computerised tomography pulmonary angiogram depending on local protocols and availability. Magnetic resonance imaging and specialized echocardiography have also been used to diagnose PE. Bilateral duplex lower limb ultrasonography should be performed if necessary.
Treatment of VTE is with heparin, which is preferred to warfarin because of the latter’s fetal effects. Intravenous unfractionated heparin has now largely been replaced by subcutaneous low-molecular-weight heparin, and this should not be delayed while awaiting investigation. Unfractionated heparin may be considered in patients with renal dysfunction, in situations where rapid reversibility of the anticoagulant action is required, and in the treatment of massive PE. Full anticoagulation precludes regional analgesia and anaesthesia (see Chapter 106, Coagulopathy) and can be a problem when pregnancy is complicated by ante- or postpartum bleeding.
In severe cases with cardiovascular instability, thrombolytic therapy may be required. The administration of potent intravenous fibrinolytic drugs in these women may result in massive obstetric haemorrhage or fetal bleeding. Some patients may require dispersion under radiological control or open embolectomy.
The use of vena caval filters in pregnancy has not been properly evaluated. Although there have been reports of the successful use of vena caval filters in pregnancy, many authors feel that their use is not justified because of the high risk of angulation and movement as a result of the pressure of the gravid uterus. However, they could be of use in women in whom anticoagulation is contraindicated or in those with recurrent VTE despite pharmacological treatment.
Thromboprophylaxis in pregnancy
Increasing numbers of women are being given prophylaxis against arterial or venous thrombosis in pregnancy. In the 2018 CEMD, one-third of deaths occurred in the antenatal period; it is therefore recommended that risk assessment for VTE should be undertaken at booking and repeated at any hospital admission, intrapartum or immediately postpartum and before discharge from hospital.
Some women have a hereditary or acquired thrombophilia or a past medical history of thrombosis. In addition, some obstetricians treat women with a history of stillbirth, intrauterine death and miscarriage with prophylactic doses of antithrombotics such as aspirin, heparin or both. Other women, for example those with prosthetic heart valves, require continuation of pre-pregnancy therapeutic doses of antithrombotics. Warfarin is teratogenic when used in the first trimester, and it is now rarely used in pregnancy. Women with metal heart valves are at particular risk of valve thrombosis and are therefore an exception (see Chapter 97, Valvular heart disease). Evaluation of women who may require anticoagulation should ideally be done before pregnancy.
Thromboprophylaxis following caesarean section
VTE occurs in around 1% of women following vaginal delivery and 2-3% following caesarean section. A significant proportion of fatal PE occurs 2-6 weeks postpartum. Guidance on the prophylaxis of VTE following caesarean section lists risk factors for which prophylactic low-molecular-weight heparin should be given. Many units prefer to treat all women as high-risk and give prophylaxis routinely unless there is a contraindication, in order to reduce the chance of omitting prophylaxis accidentally.
Increased doses of heparin are required in pregnancy and especially in obesity (Table 104.1). Neither warfarin nor heparin is excreted in breast milk.
Table 104.1 Recommended daily doses of low-molecular-weight heparin for thromboprophylaxis in pregnancy and the puerperium
|
Weight |
Enoxaparin |
Dalteparin |
Tinzaparin |
|
< 50 kg |
20 mg od |
2500 units od |
3500 units od |
|
50-90 kg a |
40 mg od |
5000 units od |
4500 units od |
|
91-130 kg |
60 mg od or 30 mg bd |
7500 units od |
7000 units od or 3500 units bd |
|
131-170 kg |
80 mg od or40 mg bd |
10,000 units od |
9000 units od or 4500 units bd |
|
> 170 kg |
0.6 mg/kg/day |
75 units/kg/day |
75 units/kg/day |
a bd if at particularly high risk.
Adapted with permission from RoyalCollege of Obstetricians and Gynaecologists. Reducing the Risk of Venous Thromboembolism during Pregnancy and the Puerperium. Green-top Guideline 37a. London: RCOG, 2015. www.rcog.org.uk/en/guidelines-research-services/guidelines/gtg37a.
Key points
• Venous thromboembolism (VTE) carries a high mortality if untreated.
• Low-molecular-weight heparin is the treatment of choice for VTE.
• Prophylaxis against VTE should be considered in all women undergoing caesarean section.
Further reading
Duran-Mendicuti A, Sodickson A. Imaging evaluation of the pregnant patient with suspected pulmonary embolism. Int J Obstet Anesth 2011; 20: 51-9.
Guimicheva B, Czuprynska J, Arya R. The prevention of pregnancy-related venous thromboembolism. Br J Haematol 2015; 168: 163-74.
Knight M, Bunch K, Tuffnell D, etal.; MBRRACE-UK. Saving Lives, Improving Mothers’ Care: Lessons learned to inform maternity care from the UK and Ireland Confidential Enquiries into Maternal Deaths and Morbidity 2014-16. Oxford: National Perinatal Epidemiology Unit, University of Oxford, 2018.
Nelson-Piercy C, on behalf of the MBRRACE-UK thrombosis and thromboembolism chapter writing group. Prevention and treatment of thrombosis and venous thromboembolism. In Knight M, Tuffnell D, Kenyon S, etal.; MBRRACE-UK. Saving Lives, Improving Mothers’ Care: Surveillance of maternal deaths in the UK 2011-13 and lessons learned to inform maternity care from the UK and Ireland Confidential Enquiries into Maternal Deaths and Morbidity 2009-13. Oxford: National Perinatal Epidemiology Unit, University of Oxford, 2015, pp. 42-52.
Royal College of Obstetricians and Gynaecologists. Reducing the Risk of Venous Thromboembolism during Pregnancy and the Puerperium. Green-top Guideline 37a. London: RCOG, 2015. www .rcog.org.uk/en/guidelines-research-services/guidelines/gtg37a (accessed December 2018).
Royal College of Obstetricians and Gynaecologists. Thromboembolic Disease in Pregnancy and the Puerperium: Acute Management. Green-top Guideline 37b. London: RCOG, 2015. www .rcog.org.uk/en/guidelines-research-services/guidelines/gtg37b (accessed December 2018).