Recommendations from guidelines for the prevention of venous thromboembolism in pregnant women with inherited thrombophilia.

Women with inherited thrombophilia represent more than 15% of the pregnant population. 20-50% of pregnancy-related venous thromboembolism (VTE) is associated with at least one inherited thrombophilia, which increases the risk of VTE up to 40-fold depending on the type of thrombophilia and the family history of VTE. Most societies consider homozygosity of factor V Leiden and the prothrombin gene mutation, compound heterozygosity of both, and severe deficiency of factor V Leiden and prothrombin gene mutation as "high risk" thrombophilia and heterozygous for factor V Leiden or the prothrombin gene mutation as "low risk" thrombophilia. Recommendations on pharmacological prophylaxis vary across international guidelines. According to expert consensus, pharmacological prophylaxis may be indicated if the risk threshold for VTE is > 3% balancing benefit against harm of heparin prophylaxis. In women with low-risk thrombophilia, guidelines recommend pharmacological prophylaxis ante- and postpartum only in cases with a positive family history of VTE or additional VTE risk factors. Most guidelines suggest heparin prophylaxis in women with homozygosity for factor V Leiden mutation or compound thrombophilia regardless of family history of VTE in the antenatal period and for 6 weeks after delivery. In women with protein S and protein C deficiencies, some guidelines advocate clinical surveillance rather than pharmacological prophylaxis antenatally, while postpartum pharmacological prophylaxis was recommended by all guidelines for women with a positive family history of VTE or with additional risk factors. Pharmacological prophylaxis in women with antithrombin deficiency remains a matter of debate and depends on the subtype and extent of antithrombin deficiency. There is yet no evidence from randomized, controlled trials that pharmacological prophylaxis significantly reduces the risk of VTE in women with inherited thrombophilia. Overestimation of the VTE risk and unnecessary use of heparin is an unsolved problem. Decision-making should also consider the increased risk of bleeding complications and wound hematoma associated with pharmacological thromboprophylaxis. Until there is more evidence for the benefit of pharmacological prophylaxis, the decision for or against prophylaxis remains a case-by-case decision taking into account the patient's individual risk profile and woman's preference.