Severe antithrombin deficiency in pregnancy: Achieving adequate anticoagulation

Abstract

Antithrombin deficiency is identified as one of the most potent risk factors for venous thromboembolism during pregnancy. Therapeutic low molecular weight heparin is recommended, but it can be difficult to attain sufficient anticoagulation since low molecular weight heparin requires antithrombin to exert its anticoagulant effect. We carried out a multicentre case-series assessing the dose of low molecular weight heparin required to achieve therapeutic anti-activated factor X levels in pregnant women with antithrombin deficiency. We assessed 27 pregnancies in 18 women with severe antithrombin deficiency, which we defined as an antithrombin level of <0.55 IU/ml (with or without prior venous thromboembolism) or an antithrombin level < 0.8 IU/ml and a personal history of venous thromboembolism. Our data illustrate the need for high doses of low molecular weight heparin to achieve therapeutic anti-activated factor X levels (average 20,220 IU/day). All pregnancies ended in live birth (excluding one elective termination), although intrauterine growth restriction occurred in five (18%).

Pregnancy complicated with deficiency of antithrombin: Review of current literature

“…The hypercoagulatory state that normally exists during pregnancy increases 4-5 times the risk of venous thromboembolism [2,29]. The incidence of pregnancy-associated venous thromboembolism is estimated at 1 in 1000 in the overall population of pregnant women [17,19]. In a pregnancy complicated with AT de iciency the risk of a thromboembolic manifestation increases from 5-10 times than in general healthy population [30].…”

“…If the level of AT functional activity is reduced to 50% -60% or less the condition is con irmed. Nevertheless, some patients can have almost adequate AT activity [5,17]. Consequently, in case of clinically suspected AT de iciency and unconvincing laboratory analyses, genetic testing of patient and family members is recommended [7].…”

“…Consecutive monitoring of hemostatic molecular markers must be performed throughout the pregnancy, because the half-life of blood AT levels changes according to gestational age [6,26]. Studies of AT levels in healthy pregnant women proved that in majority of women there are no signi icant changes in AT activity during each trimester or during the postpartum period [17,25]. However, in women with AT de iciency functional activity of AT gradually decreases as pregnancy progresses, reaching the lowest percent four days after delivery [6,17,26].…”

“…Studies of AT levels in healthy pregnant women proved that in majority of women there are no signi icant changes in AT activity during each trimester or during the postpartum period [17,25]. However, in women with AT de iciency functional activity of AT gradually decreases as pregnancy progresses, reaching the lowest percent four days after delivery [6,17,26]. Reduced activity of AT also correlates with term preeclampsia, implying that women with AT de iciency need to check blood pressure and urine protein levels even more often than generally suggested [25,27,28].…”

“…Several reports have been published about the relationship between inherited thrombophilias and adverse pregnancy outcomes [13][14][15]. Although the association between different thrombophilias and pregnancy complications is well established and con irmed, data regarding the in luence of inherited AT de iciency on pregnancy outcome are still limited and controversial [16][17][18].…”