Inherited antithrombin deficiency in pregnancy

Abstract

Inherited AntiThrombin Deficiency (ATD) is a rare and high-risk thrombophilia. It is associated with a high risk of venous thromboembolism, thrombosis, and the risk is escalated further in the prothrombotic state of pregnancy. Due to the thrombotic tendency it is also associated with placental dysfunction due to placental thrombosis. Untreated mothers with ATD have increased rates of second and third trimester loss, pre-eclampsia & eclampsia, placental abruption, and intra-uterine growth restriction resulting in small for gestational age babies.We have conducted a comprehensive review of the literature and guidelines & summarise the role of antithrombin, how to test for it, the evidence for its role in thrombosis and obstetric complications and how best to manage this. We also aim to present what we believe is best practise for managing ATD during pregnancy and therefore provide a much needed practical guide.Managing these women during pregnancy is designed to reduce their risk of thrombosis and late obstetric complications. Due to the rarity of the condition and the ethical difficulties surrounding clinical trials in pregnant women no randomised controlled trials or large observational studies have been conducted in this area; evidence is limited to small cohort studies, which are usually retrospective. Definitions such as ‘miscarriage’ and ‘fetal loss’ are also discordant between studies and associations which makes data comparison difficult. Thus there is limited guidance on the management of ATD in pregnancy. We recommend the use of low molecular weight heparin (LMWH) during pregnancy with regular anti- Xa monitoring to ensure that women receive adequate antithrombotic therapy. Due to the efficacy of LMWH working through potentiation of antithrombin, in those with ATD, high levels of LMWH are usually required. We discuss the use of antithrombin concentrates at times where the use of LMWH is contraindicated, such as during delivery.Emerging evidence suggests that the type of antithrombin deficiency is important in risk stratification along with the individual's own thrombotic risk factors, thrombosis history and family history.