Dalteparin for the prevention of recurrence of placental-mediated complications of pregnancy in women without thrombophilia: a pilot randomized controlled trial

Abstract

Summary. Background: The role of anticoagulants for the prevention of placental-mediated pregnancy complications is uncertain. Objectives: Our aim was to investigate the effectiveness of dalteparin, a low-molecular-weight heparin, in preventing the recurrence of these complications in women without thrombophilia. Patients/methods: Between August 1 2000 and June 20 2007, 116 pregnant women with: (i) £ 16 weeksÕ gestation, (ii) no detectable thrombophilia, (iii) previous severe pre-eclampsia, newborn weight £ 5th percentile, unexplained intrauterine death or abruptio placentae were randomized to either a prophylactic daily dose of dalteparin (n = 58) or no dalteparin (n = 58). The primary outcome was a composite of one or more of: severe pre-eclampsia, newborn weight £ 5th percentile or major abruptio placentae. Secondary outcomes included non-severe pre-eclampsia, newborn weight at the 6-10th percentile and gestational age at delivery. Analyses were by intention to treat. P < 0.05 was considered to be significant. This study is registered as an International Standard Randomized Controlled Trial, number ISRCTN78732833. Results: Among the 110 women included in the final analysis, dalteparin was associated with a lower rate of the primary outcome [5.5% (n = 3/55) vs. 23.6% (n = 13/55), adjusted odds ratio (OR) 0.15, 95% confidence interval (CI) 0.03-0.70]. Secondary outcomes were not statistically different between the groups. Bleeding problems or thrombocytopenia did not occur. Conclusion: In this pilot study, dalteparin is effective in decreasing the recurrence of placental-mediated complications in women without thrombophilia. Our results require confirmation in further randomized trials.

Prophylactic Low Molecular Weight Heparin Improving Perinatal Outcome in Non-thrombophilic Placental-Mediated Complications

“…There was no statistical difference in the mean gestational age of delivery between the two groups in the present study (38.05 ± 2.02 vs. 37.58 ± 2.06 weeks). Similarly, Rey et al [8] in his study did not find any difference in gestational age between cases and controls. However, Mello et al [15] observed gestational age of delivery to be 37 weeks.…”

“…These complications occur due to placental vascular thrombosis which decreases placental perfusion [5][6][7]. Several studies have reported these placental-mediated complications even in patients without thrombophilia [8].…”

How to assess and manage hypertension during and after pregnancy

“…Low-molecular-weight heparin acts as an anticoagulant by inactivating thrombin and other proteases involved in hemostasis. An improvement in pregnancy outcome has been noted in women with a history of severe pre-eclampsia if low-molecular-weight heparin was administered [61]. However, so far, routine use of low-molecular-weight heparin as a preventive agent has not been implemented in clinical practice.…”

Low molecular weight heparin for the prevention of severe preeclampsia: where next?

“…Multiple clinical trials have reported that LMWH reduced the incidence of preeclampsia, as well as newborn weight < 5th percentile, FGR, major placental abruption or fetal loss after 20 weeks' gestation [20][21][22][23][24][25][26][27]; however, other trials of similar design have demonstrated no treatment effect with LMWH [28][29][30]. Most recently, the large, well-designed HEPEPE and EPPI trials reported that enoxaparin with ASA does not significantly reduce placental-mediated complications, including preeclampsia, when compared to aspirin alone [31,32].…”