Abstract

Background: During pregnancy untreated antithrombin deficiency is associated with up to a 50% risk of venous thromboembolism (VTE) and a relative risk of pregnancy loss of 2.1 with a 5-fold increase in stillbirths. Thus thromboprophylaxis is widely used, but little data is available to select type, dose & duration of anticoagulation.

Method: We performed a retrospective, single centre observational study of our antithrombin deficient pregnancies since 1996.

Results: There were 9 pregnancies in 8 women; median age at conception 33 (age-range 19–37). They separated into 3 groups (1) 4 asymptomatic patients diagnosed on family screening. They received unmonitored enoxaparin 40mg until 16 weeks then 40mg BD. (2) 2 with previous VTE, received intermediate dose enoxaparin (1mg/kg), increased to BD at 16 weeks. Monitoring was done to maintain an anti-Xa trough of <0.12 iu/ml and peak <0.8iu.ml. (3) 2 referred after presenting with VTE in pregnancy. They received enoxaparin 1mg/kg BD and the same monitoring These included a known antithrombin deficient woman, referred in her second pregnancy at 26weeks gestation with premature rupture of the membranes and an iliofemoral deep vein thrombosis which developed on enoxaparin 60mg OD. Enoxaparin was increased to 1mg/kg BD and an IVC filter inserted. Despite the filter however she had a pulmonary embolism. The filter was removed after Caesarean section at 31 weeks. Two had sagittal sinus thromboses in the first trimester associated with severe hyperemesis requiring IV fluids. One was our only thromboprophylaxis failure, receiving enoxaparin 40mg OD, she weighed 80Kg. The second presented at 11weeks gestation. She was intolerant of self injecting and so switched to warfarin at 15 weeks until 35 weeks as did one other mother. All mothers had close feto-maternal monitoring with uterine artery Doppler at 24 weeks if possible and then monthly growth scans thereafter.

Delivery: Thromboprophylaxis was stopped at labour initiation or 12hrs prior to Caesarean section (3 women) and 50iu/kg of antithrombin concentrate was given. Anticoagulation was restarted 24hrs after delivery. Six weeks enoxaparin post-partum thromboprophylaxis was given or the women converted back to warfarin. Estimated blood loss at delivery was a median of 200ml (range 200–500ml), no transfusions were required. There were no post partum VTEs. Nine births occurred at a median gestation of 38weeks (range 31–41), median birth weight 3045g (range 1420–4120g). One child has West’s syndrome.

Conclusion: This is the largest case series on the management of antithrombin deficiency in pregnancy. The combined use of enoxaparin in pregnancy and post partum combined with antithrombin concentrate during labour appears to improve pregnancy outcome and reduce the rate of VTE. Larger studies are required to confirm this finding.

Author notes

Disclosure:Financial Information: One of the authors has received grants from Sanofi to attend medical conferences. Off Label Use: Enoxaparin and warfarin are not licensed in pregnancy but are widely used. Low moleular weight heparins are the standard of care in the UK and internationally. Although unfractionated heparin is an alternative the more predictable pharmacokinetics of low molecular weight heparins is safer in pregnancy. Research in this area is very limited and is one of the major reasons for our abstract.