Low-molecular-weight heparin added to aspirin in the prevention of recurrent early-onset pre-eclampsia in women with inheritable thrombophilia: the FRUIT-RCT

FRUIT Investigators, Marc Spaanderman

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Early-onset hypertensive disorders (HD) of pregnancy and small-for-gestational age infants (SGA) are associated with placental vascular thrombosis, these often recur and are also associated with inheritable thrombophilia. Aspirin reduces the recurrence risk.Adding low-molecular-weight heparin (LMWH) to aspirin at <12 weeks gestation reduces the recurrence of HD in women with previous early-onset HD (pre-eclampsia, hemolysis, elevated liver enzymes and low platelets [HELLP] syndrome and eclampsia) and/or SGA, in the context of inheritable thrombophilia without antiphospholipid antibodies.In a multicenter randomized control trial (RCT), 139 women included were<12 weeks gestation.previous delivery<34 weeks gestation with HD and/or SGA; inheritable thrombophilia (protein C deficiency, protein S deficiency, activated protein C resistance, factor V Leiden heterozygosity and prothrombin gene G20210A mutation heterozygosity); and no antiphospholipid antibodies detected.either daily LMWH (dalteparin, 5000 IU weight-adjusted dosage) with aspirin 80 mg or aspirin 80 mg alone.recurrent HD onset (i) <34 weeks gestation and (ii) irrespective of gestational age.recurrent SGA, preterm birth, maternal/neonatal hospitalization, spontaneous abortion and individual HD. Analysis by intention-to-treat.Low-molecular-weight heparin with aspirin reduced recurrent HD onset <34 weeks gestation (risk difference [RD] 8.7%: confidence interval [CI] of RD 1.9?15.5%; P = 0.012; number needed to treat [NNT] 12). Recurrent HD irrespective of gestational age was not different between the arms. No women withdrew as a result of adverse effects.http://www.isrctn.org) (isrctn87325378).Adding LMWH to aspirin at <12 weeks gestation reduces recurrent HD onset <34 weeks gestation in women with inheritable thrombophilia and prior delivery for HD/SGA
Original languageEnglish
Pages (from-to)64-72
JournalJournal of Thrombosis and Haemostasis
Issue number1
Publication statusPublished - Jan 2012


  • aspirin
  • low-molecular-weight heparin
  • pre-eclampsia
  • randomized controlled trial
  • thrombophilia

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