• Johanna I P de Vries, M G van Pampus, W M Hague, P D Bezemer, J H Joosten, and FRUIT Investigators.
• Department of Obstetrics and Gynaecology, VU University Medical Center, Amsterdam, the Netherlands. jip.devries@vumc.nl
• J. Thromb. Haemost. 2012 Jan 1; 10 (1): 64-72.

BackgroundEarly-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.ObjectivesAdding 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.Patients/MethodsIn a multicenter randomized control trial (RCT), 139 women included were< 12 weeks gestation.Inclusion Criteriaprevious 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.Interventioneither daily LMWH (dalteparin, 5000 IU weight-adjusted dosage) with aspirin 80 mg or aspirin 80 mg alone.Main Outcome MeasuresPrimary Outcomesrecurrent HD onset (i) < 34 weeks gestation and (ii) irrespective of gestational age.Secondary Outcomesrecurrent SGA, preterm birth, maternal/neonatal hospitalization, spontaneous abortion and individual HD. Analysis by intention-to-treat.ResultsLow-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.Trial Registrationhttp://www.isrctn.org) (isrctn87325378).ConclusionsAdding 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 <34 weeks. However, close monitoring of the mother and fetus remains important throughout pregnancy.

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