Venous thromboembolism (VTE), which may manifest as pulmonary embolism or deep vein thrombosis (DVT), is a leading cause of maternal morbidity and mortality in developed countries, such as the UK and United States. Though, its absolute rates are low. Up to now, there are a total of fifteen guidelines from 13 organizations worldwide focused on VTE prevention and treatment in pregnancy and puerperium; however, no Chinese guidelines developed yet. China is now experiencing disease profile changing. With the release of the two-child policy, more and more women in China enter pregnancy in an advanced age and high weight, with previous history of cesarean section or through assisted reproductive technology, such as in vitro fertilization (IVF). Thus, increasing consideration of DVT screening and therapy in pregnancy and developing documents to provide information regarding the risk factors, diagnosis, management, and prevention of VTE in pregnancy are essential in China. For this purpose, a round table meeting with delegates from five countries was held during the First International Forum on Chinese Maternal-Fetal Medicine, discussing DVT guidelines and expert opinions in pregnancy existing. The following is a brief overview of the discussion.
Evidence has shown that compared to non-pregnant women of comparable age, women during pregnancy have five- to ten-fold increased risk of VTE,1,2 and the VTE risk increases with gestational weeks, reaching a maximum just after delivery.2,3 That may be due to the reason that pregnancy and puerperium mean increased hypercoagulable states.2,4 Furthermore, additional risk factors, like pre-existing histories of VTE, pregnancy complications, and so on can contribute to increased pregnancy-related risk of VTE.2–4 A personal history of thrombosis is considered to be the most important individual risk factor for VTE in pregnancy, and the second risk factor is the presence of a thrombophilia. Besides, cesarean delivery, obesity, chronic hypertension, preeclampsia, autoimmune disease, heart disease, sickle cell disease, and multiple gestation also increase the risk of VTE. Thus, early clinical evaluation, preferably in peri-conceptional period, is crucial for VTE risk detection and prophylaxis decision making. Moreover, a risk re-assessment should always be taken into consideration due to the ongoing medical changes during pregnancy.2–4
Maternal morbidity surveys showed that VTE thromboprophylaxis brought significant advantages in pregnancy outcomes and maternal deaths. Antepartum and/or postpartum treatment or prophylaxis is indicated in women with: (1) personal and/or family history for VTE events; (2) well documented thrombophilia; (3) maternal-fetal conditions that imply higher VTE risk; (4) surgery in pregnancy or cesarean section (due to perioperative risks such as immobility, inflammatory state, infection, etc). Moreover, an emerging high risk group–IVF pregnancies should also be accounted.5 The antepartum risk of VTE in IVF pregnancies is considered to be doubled compared with the background pregnant population. Furthermore, studies confirmed that ovarian hyperstimulation in relation to IVF showed a 100-fold risk for VTE. Thus, though there is no unanimous consensus on VTE thromboprophylaxis in IVF pregnancies, experts recommend that IVF patients with ovarian hyperstimulation syndrome be prescribed low-molecular-weight heparin (LMWH) during the first trimester, whereas other IVF patients should be given thromboprophylaxis based on the same risk factors as other pregnant women.
Common pharmacological and mechanical forms of thromboprophylaxis includes heparin compounds, anti-embolic stockings and intermittent pneumatic compression devices.2–4 For heparin compounds, based on prediction models and expert opinions, most guidelines recommend LMWH as first line strategy,2–4 because LMWH has been associated with fewer adverse effects, such as fewer bleeding episodes and less bone mineral density loss. Furthermore, LMWH is considered to be more effective and easier to administer, and has a lower risk of heparin-induced thrombocytopenia and longer half-life. All women should undergo risk factor assessment for VTE in early pregnancy or in prepregnancy period, and the risk of VTE should be always discussed, especially at admission to the hospital or if a pregnancy complication develops. Then, by reviewing the available VTE risk assessment protocols and adopting and implementing proper thromboprophylaxis to reduce the incidence of VTE in pregnancy and the postpartum period. Moreover, patient's awareness, adherence, and compliance to medical instructions should also been assessed and considered during pregnancy and postpartum.
Current guidelines or expert opinions on VTE treatment or prophylaxis during pregnancy diverge significantly on the VTE diagnostic scores, risk stratification, evaluation of thromboprophylaxis indications, and dosages and duration of prophylaxis.6 For example, for identifying patients that should receive pharmacologic thromboprophylaxis post-cesarean, the American Congress of Obstetricians and Gynecologists (ACOG),3 the Royal College of Obstetricians and Gynecologists (RCOG),4 and the American College of Chest Physicians (CHEST)7 differ substantially. Under RCOG guidelines, 85.0% of patients would receive post-cesarean pharmacologic prophylaxis compared with 1.0% of patients under ACOG guidelines and 34.8% of patients under Chest guidelines. That is because, ACOG recommends postpartum pharmacologic prophylaxis for only women with a high-risk of thrombophilia, a prior VTE event, and/or a strong family history of VTE. Chest recommends no prophylaxis for low-risk women delivered by cesarean and recommends pharmacologic prophylaxis for women with risk factors such as infection, preeclampsia, and obesity. While, recommendations from RCOG are the most conservative and suggest pharmacologic prophylaxis for the largest proportion of patients, including women who are older than 35, obese (body mass index >30 kg/m2) or had a cesarean section. Thus, for China, developing its own strategies for screening, prevention, and treatment of VTE based on different guidelines existing is of great importance.
Conclusively, although our knowledge of risk factors for pregnancy-related VTE and the safe and effectiveness of anticoagulants used to prevent and treat VTE in pregnancy continues to increase, there are still important gaps and high quality research in this area should be a priority. The main conflicting recommendations were mainly at the anticoagulant choice for prevention during pregnancy and after cesarean section. The duration of VTE treatment in pregnant women was also controversial. In the interim, all women should be provided with the opportunity to participate in shared decision making regarding their management. To make the best decisions, absolute risks and potential benefits of VTE thromboprophylaxis should be evaluated. Moreover, guideline recommendations and patient values and preferences should all be taken into account.
Conflicts of Interest
. Bourjeily G, Paidas M, Khalil H, et al. Pulmonary embolism in pregnancy
. Lancet 2010;375(9713):500–512. doi:10.1016/S0140-6736(09)60996-X.
. Bates SM, Middeldorp S, Rodger M, et al. Guidance for the treatment and prevention of obstetric-associated venous thromboembolism
. J Thromb Thrombolysis 2016;41(1):92–128. doi:10.1007/s11239-015-1309-0.
. ACOG Practice Bulletin No. 196 Summary: Thromboembolism in pregnancy
. Obstet Gynecol
. Royal college of Obstetricians and Gynaecologists. Thromboembolic Disease in Pregnancy
and the Puerperium: Acute Management (Green-Top Guideline No.37b). 2015. Available at: https://www.rcog.org.uk/en/guidelines-research-services/guidelines/gtg37b/
. Rova K, Passmark H, Lindqvist PG. Venous thromboembolism
in relation to in vitro fertilization: an approach to determining the incidence and increase in risk in successful cycles. Fertil Steril 2012;97(1):95–100. doi:10.1016/j.fertnstert.2011.10.038.
. Palmerola KL, D’Alton ME, Brock CO, et al. A comparison of recommendations for pharmacologic thromboembolism prophylaxis
after caesarean delivery from three major guidelines. BJOG 2016;123(13):2157–2162. doi:10.1111/1471-0528.13706.
. Bates SM, Greer IA, Middeldorp S, et al. VTE, thrombophilia, antithrombotic therapy, and pregnancy
: antithrombotic therapy and prevention of thrombosis, 9th ed: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines. Chest 2012;141(2 Suppl):e691S–e736S. doi:10.1378/chest.11-2300.