European Journal of Obstetrics & Gynecology and Reproductive Biology 80 (1998) 49–54 Low-molecular-weight heparin combined with aspirin in pregnant women with thrombophilia and a history of preeclampsia or fetal growth restriction: a preliminary study a a a b Naghmeh Riyazi , Michal Leeda , Johanna I.P. deVries , Peter C. Huijgens , Herman P. van a a, * Geijn , Gustaaf A. Dekker a Division of Maternal –Fetal Medicine, Department of Obstetrics and Gynecology, Free University Hospital, De Boelelaan 1117, 1081 HV Amsterdam, The Netherlands b Division of Maternal –Fetal Medicine, Department of Hematology, Free University Hospital, Amsterdam, The Netherlands Received 13 November 1997; received in revised form 26 February 1998; accepted 26 March 1998 Abstract Objective: To assess the prevalence of haemostatic abnormalities in patients with an obstetric history of preeclampsia and / or fetal growth restriction and documented thrombophilia, and to evaluate the effects of low-molecular-weight heparin (LMWH) and aspirin on pregnancy outcome. Method: A total of 276 patients with a history of preeclampsia and / or fetal growth restriction were tested for the presence of coagulation abnormalities and anticardiolipin antibodies (ACA). Ninety patients with preeclampsia and 15 patients with isolated fetal growth restriction had haemostatic abnormalities. Twenty-six patients with coagulation abnormalities: protein S-deficiency, activated protein C (APC) resistance and / or $15 ACA GPL and / or MPL had a subsequent pregnancy and were treated with aspirin in combination with LMWH. Their pregnancy outcome was compared with all patients having a subsequent pregnancy from the same cohort without abnormalities, or ,15 ACA GPL and / or MPL who received aspirin ( n519). Results: In subsequent pregnancies birth weight of babies born to patients with an unequivocal coagulation abnormality (i.e., protein S-deficiency, APC resistance, or ACA titres $15 GPL and/or MPL), were higher than in the group with no disorders or ,15 ACA GPL and/or MPL (P50.019). Conclusions: In this preliminary study, LMWH appears to have a favourable effect on the pregnancy outcome of women with a history of preeclampsia and / or fetal growth restriction and documented thrombophilia. Randomised trials are required  1998 Elsevier Science Ireland Ltd Keywords: Uteroplacental insufficiency; Thrombophilia; Heparin; Anticardiolipin antibodies 1. Introduction preeclampsia have a high recurrence rate of preeclampsia in subsequent pregnancies, rates up to 65% being reported. Hypertensive disorders of pregnancy are the leading Low-dose aspirin reduces, to some extent, the incidence of cause of maternal and perinatal mortality and morbidity in recurrent preeclampsia in subsequent pregnancies [5]. The developing and developed countries [1]. The aetiology of management of patients with uteroplacental insufficiency, preeclampsia remains unknown. However, Dekker et al. i.e., preeclampsia and fetal growth restriction in the [2] recently demonstrated that severe preeclampsia is obstetric history, and documented thrombophilia is still frequently associated with underlying metabolic and / or undefined [6,7]. We, therefore, initiated this retrospective haemostatic abnormalities. Several studies [3,4] have study, in order to confirm: (a) in a large group of more than demonstrated, that patients with early onset and severe 205 women, the earlier findings [2]; (b) to assess if haemostatic abnormalities are also involved in patients * with an obstetric history of isolated fetal growth restric- Corresponding author. Tel.: 131 20 4444444*98104; Fax: 131 20 4444645. tion; and finally (c) to evaluate the effect of a combination 0301-2115 / 98 / $19.00  1998 Elsevier Science Ireland Ltd All rights reserved. PII: S0301-2115(98)00083-9