Anticoagulants in pregnancy

The key consideration for anticoagulant treatment in pregnancy is the potential for any effect on the fetus, both in terms of impact on development and also any anticoagulant effect consequent upon placental transfer.

Warfarin and other vitamin K antagonists cross the placenta. These agents have a potential teratogenic effect, specifically warfarin embryopathy (midface hypoplasia, short proximal limbs, short phalanges, and scoliosis), which complicates a small number of pregnancies exposed to warfarin in the first trimester.

Table 16.1 Risk factors for gestational venous thromboembolism

Patient factors	I Pregnancy factors
Previous VTE****	Twin pregnancy**
Immobility***	Antepartum haemorrhage**
BMI>30 kg/m²***	Postpartum haemorrhage (>1 L)***
Weight >120 kg**	Caesarean section**
Smoking (10-30 cigarettes a day before or during pregnancy)**	Pre-eclampsia**
Weight gain >21 kg (vs 7-21 kg)*	Pre-eclampsia with fetal growth restriction***
Parity >1*	Assisted reproductive techniques/*
Age >35 years*	Blood transfusion**
Medical conditions,³ e.g. SLE, heart disease, anaemia, sickle cell disease, active infection, varicose veins	Hyperemesis**
Thrombophilia^b	Postpartum infection***

Typical estimates risk: odds ratios: **** >20; *** >4; ** >2; * >1.

^a Wide range of risk according to type and severity of medical condition (14).

^b See Table 16.2 for levels of risk.

Source data from Jacobsen AF, Skjeldestad FE, Sandset PM. Ante- and postnatal risk factors of venous thrombosis: a hospital-based case-control study. J Thromb Haemost 2008; 6(6):905-912, Greer IA. Thrombosis in pregnancy: updates in diagnosis and management. Hematology Am Soc Hematol Educ Program 2012;2012:203-7, Bates SM, Greer IA, Middeldorp S, Veenstra DL, Prabulos AM, Vandvik PO. VTE, Thrombophilia, Antithrombotic Therapy, and Pregnancy. Chest 2012;141(2)(Suppl):e691S-e736S, Robertson L, Wu O, Langhorne P, et al. Thrombosis Risk and Economic Assessment of Thrombophilia Screening (TREATS) Study. Thrombophilia in pregnancy: a systematic review. BrJ Haematol 2005;132 :171-96, James AH, Jamison MG, Brancazio LR, Myers ER. Venous thromboembolism during pregnancy and the postpartum period: incidence, risk factors, and mortality. AmJ Obstet Gynecol 2006;194:1311-15 and Royal College of Obstetricians and Gynaecologists. Green-top Guideline No. 37a. Reducing the risk of thrombosis and embolism during pregnancy and the puerperium (April 2015). https:// www.rcog.org.uk/en/guidelines-research-services/guidelines/gtg37a/. this situation, it is still best to avoid warfarin in the first trimester where possible. For women on long-term oral anticoagulation it is important to discontinue this (and replace with unfractionated heparin (UFH) or low-molecular-weight heparins (LMWHs)) where possible by 6 weeks' gestation to avoid the risk of embryopathy. However, as warfarin does not cross into breastmilk, it can be used postpartum (11). Outside of pregnancy, oral direct thrombin and factor Xa inhibitors are increasingly being used; however, their effects and risks in pregnancy have not been established (11, 17). Given the established safety of alternative established treatments (UFH and LMWH), these agents should generally be avoided in pregnancy.

Fondaparinux appears to cross the placenta in small quantities; however, adverse effects have not been described in the increasing number of reports describing its use in pregnancy, particularly in situations where LMWH cannot be used (17-19). It should be noted that most reports on fondaparinux relate to second- and third-trimester use.

In contrast to warfarin, UFH and LMWH do not cross the placenta and therefore do not pose a direct risk to the fetus (11). LMWH has a better safety profile than UFH (5, 9-11, 20, 21) in terms of bleeding complications, heparin-induced thrombocytopenia, and heparin-associated osteoporosis. A systematic review of 18 studies with 981 pregnant women with acute VTE reported a mean incidence of major antenatal bleeding of 1.41% (95% CI 0.60-2.41%), 1.90% (95% CI 0.80-3.60%) in the first 24 hours after delivery, 1.2% (95% CI 0.30-2.50%) for major postpartum bleeding after 24 hours, and 1.97% (95% CI 0.88-3.49%) for recurrent VTE in pregnancy (21). There is a risk of accumulation of LMWH in women with significant renal dysfunction, as these agents depend on renal excretion and dose adjustment may be required in this situation.

With discontinuation of vitamin K antagonists prior to 6 weeks' gestation, the risk of warfarin embryopathy is avoided (11). There are also associations with pregnancy loss and neurodevelopmental deficits (11), and risks from fetal anticoagulation. While generally warfarin should be avoided in pregnancy, there are some high-risk situations where, because of a high risk of maternal thrombosis that is thought to outweigh the fetal risk, warfarin can be considered. In

Table 16.2 Relative risk of gestational venous thromboembolism in asymptomatic women with heritable thrombophilia

Thrombophilia	Typical relative risk for non-familial studies Odds ratio (95% confidence interval)
Antithrombin deficiency	4.7(1.3-17.0)
Protein C deficiency	4.8(2.2-10.6)
Protein S deficiency	3.2(1.5-6.9)
Factor V Leiden, heterozygous	8.3 (5.4-12.7)
Factor V Leiden, homozygous	34.4 (9.9-120.1)
Prothrombin G20201A, heterozygous	6.8(2.5-18.8)
Prothrombin G20201A, homozygous	26.4 (1.2-559.3)

Source data from 12. Robertson L, Wu O, Langhorne P, et al. Thrombosis Risk and Economic Assessment of Thrombophilia Screening (TREATS) Study, Thrombophilia in pregnancy: a systematic review, BrJ Haemato12005;132(2):171-196.

<< | >>

↑

Source: Arulkumaran S., Ledger W., Denny L., Doumouchtsis S. (eds.). Oxford Textbook of Obstetrics and Gynaecology. Oxford University Press,2020. — 928 p.. 2020

More medical literature on Medic.Studio

Anticoagulants in pregnancy

More on the topic Anticoagulants in pregnancy: