title: Adjusting enoxaparin dosage according to anti-FXa levels and pregnancy outcome in thrombophilic women. A randomised controlled trial.
abstract: Women with thrombophilias and previous placenta-mediated pregnancy complications (PMPC) have an increased risk of both recurrent PMPC and venous thromboembolism (VTE) during subsequent pregnancies. We aimed to examine whether enoxaparin dose adjusted according to anti-factor Xa levels compared to a fixed dose would reduce the risk of PMPC in subsequent pregnancies. In a randomised trial, conducted at a single teaching hospital, pregnant women with thrombophilia and previous PMPC were enrolled in a 1:1 ratio to either a fixed dose of 40 mg daily enoxaparin or adjusted dose according to anti-factor Xa plasma levels. The primary outcome was a composite that included any of the following: pregnancy loss after enrollment, pre-eclampsia, birthweight <10th percentile, placental abruption, or VTE. Overall, 144 women were needed to detect a decrease of 20 % in the incidence of the composite outcome among the adjusted dose group. Between 2009 and 2015, 144 women consented; four in the fixed-dose group were excluded. Overall, 66 and 74 in the fixed- and adjusted-dose groups, respectively, were included. Demographic and obstetric characteristics were comparable. Composite outcome occurred in 12 (18.2 %) and 20 (27.0 %) women in the fixed- and adjusted-dose groups, respectively (p=0.24). Gestational age at delivery, preterm births, and birthweights were similar between the two groups. In conclusion, dose of enoxaparin adjusted according to anti-factor Xa levels compared to fixed dose, does not reduce the risk of PMPC recurrence in thrombophilic women.
authors.affiliation: Raed Salim, MD, Department of Obstetrics and Gynecology, Emek Medical Center, Afula 18101, Israel, Tel.: +972 4 649 4031, E-mail: salim_ra@clalit.org.il.
authors.forename: Raed
authors.initials: R
authors.lastname: Salim
authors.forename: Zohar
authors.initials: Z
authors.lastname: Nachum
authors.forename: Israel
authors.initials: I
authors.lastname: Gavish
authors.forename: Shabtai
authors.initials: S
authors.lastname: Romano
authors.forename: Meirav
authors.initials: M
authors.lastname: Braverman
authors.forename: Gali
authors.initials: G
authors.lastname: Garmi
mesh_terms: D000328:Adult; D000925:Anticoagulants; D001724:Birth Weight; D017984:Enoxaparin / Q000008:administration & dosage*; D065427:Factor Xa Inhibitors / Q000097:blood*; D005260:Female; D006801:Humans; D007231:Infant, Newborn; D011225:Pre-Eclampsia; D011247:Pregnancy; D011250:Pregnancy Complications, Hematologic / Q000188:drug therapy*; D011256:Pregnancy Outcome; D011725:Pyridines; D019851:Thrombophilia / Q000188:drug therapy*; D054556:Venous Thromboembolism
chemical_list: D000925:Anticoagulants; D017984:Enoxaparin; D065427:Factor Xa Inhibitors; D011725:Pyridines; C108850:V 10367
keywords: Anti-factor Xa; low-molecular-weight heparin; placenta-mediated pregnancy complications; thrombophilia