Prophylaxis of venous thromboembolism
There is considerable variability between guidelines on the use of prophylactic anticoagulants for VTE. This is because of an insufficient evidence base to inform the estimated risk of gestational VTE and associated risk reduction with prophylaxis, the burdens of longterm (parenteral) anticoagulant therapy, and patient and physician values and preferences.
Guidelines are based on evidence obtained from a small number of trials, observational studies, or extrapolated from the non-pregnant situation. An individual risk-benefit assessment is needed when considering thromboprophylaxis with shared decision-making with the woman regarding her preferences and values. Underlining the need for better evidence, the most recent Cochrane systematic review of thromboprophylaxis in pregnancy and the puerperium concluded that the current available evidence is insufficient to make firm recommendations, based on 2592 women in 16 randomized trials (22). The common risk factors for VTE are set out in Tables 16.1 and 16.2. Lack of knowledge of how these interact, but an awareness that they do and that the interactions are not simply arithmetic, has led to a pragmatic approach in guidelines based on magnitude and number of risk factors. There is consistency, however, on a preference for long-term subcutaneous LMWH for prophylaxis. Table 16.3 summarizes existing guidance for thromboprophylaxis according to the clinical features (11, 14, 23). When prophylaxis with LMWH is used, there is also uncertainty regarding duration, particularly postpartum. Mechanical prophylaxisTable 16.3 Suggested prophylaxis of venous thromboembolism in pregnancy based on guidelines
| Patient group | Suggested’ period of prophylaxis | Suggested’ thromboprophylactic agent and management |
| All pregnant women with previous VTE | Postpartum prophylaxis for 6 weeks | Prophylactic or intermediate-dose LMWHb or vitamin K antagonists targeted at INRc 2.0 |
| Pregnant women at low risk of recurrent VTE (single previous VTE associated with a transient risk factor not related to pregnancy or use of oestrogen such as with the combined oral contraceptive pill) | NA | Clinical vigilance antepartum rather than antepartum prophylaxis (note that if multiple additional risk factors are present, these may lead to antepartum prophylaxis with prophylactic or intermediate-dose LMWH) |
| Pregnant women at moderate to high risk of recurrent VTE because of (a) previous single VTE that was unprovoked or pregnancy or oestrogen related; (b) multiple previous unprovoked VTE not receiving long-term anticoagulation | Antepartum from diagnosis of pregnancy | Prophylactic or intermediate-dose LMWHb |
| Pregnant women receiving long-term vitamin K antagonists | Antepartum from diagnosis of pregnancy (switching to LMWH before 6 weeks' gestation if possible to avoid embryopathy risk) | Therapeutic-dose LMWH or 75% of a therapeutic dose of LMWH followed by resumption of vitamin K antagonists postpartum |
| Pregnant women with (a) no previous VTE and (b) homozygous for factor V Leiden or the prothrombin 20210A mutation and (c) have a positive family history for VTE | Throughout the antepartum period from diagnosis of pregnancy and postpartum prophylaxis for 6 weeks | Antepartum: prophylactic- or intermediate-dose LMWH. Postpartum: prophylactic- or intermediate-dose LMWH or vitamin K antagonists targeted at INR 2.0-3.0 |
| Pregnant women with all other heritable thrombophilias and no prior VTE who have a positive family history for VTE | Postpartum prophylaxis for 6 weeks | Antepartum: clinical vigilance Postpartum: prophylaxis with prophylactic or intermediate-dose LMWH |
| Pregnant women with no previous VTE and known to be homozygous for factor V Leiden or the prothrombin 20210A mutation and who do not have a positive family history for VTE | Postpartum prophylaxis for 6 weeks | Antepartum: clinical vigilance Postpartum: prophylactic or intermediate-dose LMWH or vitamin K antagonists targeted at INR 2.0-3.0 |
| Pregnant women with all other thrombophilias and no previous VTE and no family history for VTE | NA | Antepartum and postpartum clinical vigilance rather than pharmacological prophylaxis |
| Women at increased risk of VTE after caesarean section because of the presence of one major or at least two minor risk factorsd | Postpartum while in hospital following delivery | Prophylactic LMWH or mechanical prophylaxis (elastic stockings or intermittent pneumatic compression) if heparin contraindicated. Elastic stockings may be combined with LMWH for those considered at very high risk for VTE |
| Women at high-risk because of significant risk factors persisting following delivery | Extended prophylaxis (up to 6 weeks following delivery) | Prophylactic LMWH. Elastic stockings may be combined with LMWH for those considered at very high risk for VTE |
| Women with multiple risk factors (≥3 antenatal or ≥2 postpartum) or with absolute risk considered >1% | Antepartum prophylaxis and postpartum prophylaxis for 6 weeks | Prophylactic LMWH. Elastic stockings may be combined with LMWH for those considered at very high risk for VTE |
a 'Suggested' rather than recommended due to lack of direct evidence.
b Prophylactic LMWH given subcutaneously once daily: examples—dalteparin 5000 units, enoxaparin 40 mg, tinzaparin 4500 units. (Note that at extremes of body weight, modification of dose may be required). Intermediate-dose LMWH: for example, dalteparin 5000 units or enoxaparin 40 mg subcutaneously twice daily, c INR: international normalized ratio
d Major risk factors (OR ≥6): the presence of at least one risk factor suggests a risk of postpartum VTE >3% following caesarean section: immobility, postpartum haemorrhage >1000 mL with surgery, previous VTE, pre-eclampsia with fetal growth restriction, thrombophilia (antithrombin deficiency, factor V Leiden (homozygous or heterozygous), prothrombin G20210A (homozygous or heterozygous)), medical conditions (systemic lupus erythematosus, heart disease, sickle cell disease, blood transfusion, postpartum infection. Minor risk factors (OR ≥6 when combined): the presence of at least two risk factors or one risk factor in the setting of emergency caesarean section suggests a risk of postpartum VTE >3% following caesarean section: BMI >30 kg/m2, multiple pregnancy, postpartum haemorrhage >1 L, smoking >10 cigarettes/day fetal growth restriction, thrombophilia (protein C deficiency, protein S deficiency), pre-eclampsia.
Source data from 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, 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.rcogThrg.uk/en/guidelinesThesearchTheMces/guidelines/gtg37a/, and Chan WS, Rey E, Kent NE; VTE in Pregnancy Guideline Working Group, Chan WS, Kent NE, Rey E, Corbett T, David M, Douglas MJ, Gibson PS, Magee L, Rodger M, Smith RE. Venous thromboembolism and antithrombotic therapy in pregnancy,J Obstet Gynaecol Can 2014;36(6):527-53.
with graduated elastic compression stockings is an alternative treatment where there are contraindications to the use of anticoagulants, or as additional prophylaxis in those women considered at high risk. Women considered at significant risk of VTE should be advised of the features of VTE so that they can seek specific medical assessment should such features arise.