Epidemiology, risk factors, and clinical features
Venous thromboembolism (VTE) is a leading cause of direct maternal mortality with a substantial number of deaths associated with inadequate approaches to prevention and management of this condition in pregnancy (1).
However, it is not just mortality that is important as there is significant morbidity from gestational VTE, due not only to thrombosis per se, but also haemorrhagic problems with therapeutic anticoagulation, and an impact on management of delivery for women with a recent VTE who are on therapeutic anticoagulation. Long-t erm sequelae include recurrent VTE and post-thrombotic syndrome, as well as an impact on use of hormonal contraception and hormone-replacement therapy in later life (2). Providing sound prophylaxis or management of VTE in pregnancy can impact outcome, with recent reports suggesting that it is associated with reduced mortality (1) and morbidity (3). In the United Kingdom's most recent report on maternal mortality, VTE was the most common cause of direct maternal death with an incidence of 1.08 (95% confidence interval (CI) 0.71-1.59) per 100,000 maternities (4). The overall reported incidence of gestational VTE varies considerably depending on the population studied, but ranges from 0.5 to 2.2 per 1000 (3, 5, 6). In relative terms, there is a 5- to 10-fold increase in the risk of VTE during pregnancy, increasing to a daily risk of 15-35-fold in the puerperium, compared with nonpregnant women of similar age (5). The risk of VTE appears greatest during the first 3 weeks following delivery when 80% of postpartum events occur (6, 7), then declines, although there may be a small increase in risk persisting for up to 12 weeks after delivery (8).Clinically, it is important to recognize that there are important considerations for VTE in pregnancy that set it apart from VTE in the non-pregnant. Deep venous thrombosis (DVT) in pregnancy is usually left sided (85% in pregnancy vs 55% in non-pregnant), and proximal (72% iliofemoral in pregnancy vs 9% in the non-pregnant) (9).
The latter point is important as there is greater potential for thromboembolism from proximal DVT, and also post-thrombotic problems are more likely. The majority of women with VTE in pregnancy have non-specific symptoms and signs, such as leg swelling or breathlessness. These can also occur with the physiological changes of pregnancy, so making clinical diagnosis unreliable and objective diagnosis is required (9, 10). Non-specific lower abdominal pain can occur with extension of thrombus into the pelvic veins or venous distension through the collateral circulation in the pelvis including around the ovary (10).The increase in risk of VTE in pregnancy is considered due to venous stasis, procoagulant changes, suppressed fibrinolysis, and endothelial injury in the course of delivery (9). Risk factors often exaggerate one or more of these components, and clinical events tend to occur when multiple risk factors coexist (10). The most commonly encountered risk factors are shown in Table 16.1 (see Table 16.2 for levels of risk). Previous VTE with a relative risk of over 20-fold (3, 13) is one of the most important risk factors. There are limited data on how these risks interact, but estimates suggest that the interaction leads to a high level of risk. For example, immobility with strict bedrest for at least 1 week in the antenatal period with a pre-pregnancy body mass index (BMI) of at least 25 kg/ m2 has been estimated to carry a 62-fold increase in VTE risk (5). These risk factors inform the use of thromboprophylaxis which is used where risk is considered to be significant as set out in various guidelines (5, 11, 14).
While heritable thrombophilia in general is a risk factor, the magnitude of risk varies with the type of heritable or acquired thrombophilia (11, 14). Furthermore, the absolute risk is often modest. For example, in non-familial studies of antithrombin and protein C and protein S deficiencies, the estimated absolute risk is less than 1%, and for heterozygous factor V Leiden and prothrombin G20210A is around 1%. The absolute risk is higher in homozygotes; however, estimates still place the risk at under 5% (5). There are data suggesting that a positive family history of VTE in women with thrombophilia is associated with a two- to fourfold higher risk of VTE (15, 16).