Inherited antithrombin deficiency and pregnancy: Maternal and fetal outcomes Jordi Sabadell a, * , Manel Casellas a , Jaume Alijotas-Reig b , Eduardo Arellano-Rodrigo c , Luis Cabero a a High Risk Pregnancy Unit, Department of Obstetrics and Gynecology, Hospital Universitari Vall d’Hebron, Passeig Vall d’Hebron 119-129, E-08035 Barcelona, Spain b Systemic Autoimmune Disease Unit, Department of Internal Medicine, Hospital Universitari Vall d’Hebron, Passeig Vall d’Hebron 119-129, E-08035 Barcelona, Spain c Department of Haematology, Hospital Universitari Vall d’Hebron, Passeig Vall d’Hebron 119-129, E-08035 Barcelona, Spain 1. Introduction Antithrombin (AT),also known as antithrombin (AT)-III, is an important natural anticoagulant that is synthesized in the liver and endothelial cells. It is the main inhibitor of thrombin and also inhibits the activated clotting factors X, IX, XI, XII and tissue factor- bound VIIa. Its inhibitory activity is increased 5000–40,000-fold in the presence of heparin [1]. Antithrombin deficiency was the first inherited thrombophilia identified,and it is the most thrombo- genic among them. Its estimated prevalencein the general population is one in 600–1000. Lifetime risk of suffering a thromboembolic episode without treatment is thought to be over 70–90% [2,3]. In addition, pregnancy providesa procoagulant state that increases the risk of suffering a venous thromboembolism (VTE), and imposes a risk 4–5 times higher than women who are not pregnant [4]. Thrombotic risk is increased among women with AT deficiency,being globally 60% during pregnancy and 30% in the puerperium [3]. During the last decade severalreports have been published about the relation between inherited thrombophilias and adverse pregnancy outcomes [4–8]. However, published data about the influence of inherited AT deficiency on pregnancy outcome are limited and controversial.The main objective of this study is to describe the effect of inherited AT deficiency on pregnancy outcome. 2. Patients and methods A retrospective descriptive study was performed among women with known inherited AT deficiency and at least one pregnancy looked after in our tertiary reference hospital during 1991–2005.Women were looked after jointly by the Obstetrics and Haemostasis Departments ofthe Vall d’Hebron University Hospital of Barcelona, Spain.Relatives with known AT deficiency but no pregnancies looked after in our centre were excluded. Each pregnancy was considered as an independent episode. This study was approved by the Ethical Committee of the Vall d’Hebron Hospital. European Journal of Obstetrics & Gynecology and Reproductive Biology 149 (2010) 47–51 A R T I C L E I N F O Article history: Received 28 April 2009 Received in revised form 8 November 2009 Accepted 7 December 2009 Keywords: Inherited thrombophilia Antithrombin deficiency Pregnancy Venous thromboembolism Stillbirth A B S T R A C T Objective: To describe the outcome of pregnancy in women with inherited antithrombin (AT) deficiency. Study design: A descriptive retrospective study was performed. Medical records were reviewed in order to collect data about maternalthrombotic complications and pregnancy outcomes. All women with known inherited AT deficiency and at least one pregnancy looked after at the Vall d’Hebron University Hospital were included.Relatives with known AT deficiency but no pregnancies looked after in our institution were excluded. Eighteen pregnancies were registered among nine AT-deficient women during 1991–2005. This cohort included women without antithrombotic treatment because AT deficiency was not known at the time of their pregnancies. Results:In 12 pregnancies (66.7%) anticoagulant therapy with low-molecular weight heparin was given, while not in the other six (33.3%) because AT deficiency was not known at this time. Three episodes of venous thromboembolism were recorded (16.7%). Among all pregnancies 10 suffered an adverse outcome (55.6%),including miscarriage (11.1%),stillbirth (11.1%), intrauterine growth restriction (33.3%),placentalabruption (6.7%),preeclampsia (6.7%) and intrapartum fetal distress (23.1%).No relation between AT activity and pregnancy complications was found. A lower incidence of pregnancy complications was observed among women with antithrombotic treatment. Conclusions:Inherited antithrombin deficiency is associated with a high risk of venous thromboembo- lism during pregnancy and the puerperium.We also observed a high incidence ofpoor pregnancy outcome among AT-deficient women. ß 2009 Elsevier Ireland Ltd. All rights reserved. * Corresponding author. Tel.: +34 93 4893066; fax: +34 93 4893066. E-mail address: jsabadga@yahoo.es (J. Sabadell). Contents lists available at ScienceDirect European Journal of Obstetrics & Gynecology and Reproductive Biology j o u r n a l h o m e p a g e : w w w . e l s e v i e r . c o m / l o c a t e / e j o g r b 0301-2115/$ – see front matter ß 2009 Elsevier Ireland Ltd. All rights reserved. doi:10.1016/j.ejogrb.2009.12.004