BACKGROUND AND OBJECTIVES: The aim of the present study was to evaluate inherited thrombophilic factor V Leiden and factor II A20210 mutations in women presenting with abruption of a normally implanted placenta. DESIGN AND METHODS: In a multi-center, case-control study, 50 consecutive women requiring immediate delivery because of abruption of the placenta were enrolled. Inclusion criteria were: abruptio placentae requiring immediate delivery, normally implanted placenta, Caucasian ethnic background, parity <3, delivery performed at Institutions. Exclusion criteria were: history of thromboembolism, history of 2 or more spontaneous abortions, uterine leiomyomas with a diameter >5 cm, illicit drug abuse, premature rupture of membranes, multiple pregnancy. One hundred Caucasian women with uneventful pregnancies carried to term, matched for parity and age, served as controls. RESULTS: Heterozygotes were found to be significantly more prevalent among women with abruptio placentae than among controls. The carriership of the FV Leiden mutation confers a OR of 9.12 (95% C.I.: 2.18-31.7; p=0.0005). Women carrying F II A20210 mutation have a OR of 12.25 (95% C.I.: 2.36-29.6; p=0.0004). No homozygotes or double heterozygotes were found. Twenty-three patients (46%) also met the criteria for a diagnosis of pre-eclampsia (PE). In such cases the prevalence of mutations (factor V: 6 cases, 26.1%; factor II: 5 cases, 21.7%) was similar to that in women without pre-eclampsia (factor V: 5 cases, 18.7%; factor II: 5 cases, 18.5%). INTERPRETATION AND CONCLUSIONS: The presence of either of the above reported thrombophilic mutations represents a relevant risk factor for the occurrence of placental abruption in Caucasians. This risk is independent of the development of pre-eclampsia. Patients who have had dramatic abruption of a normally implanted placenta should undergo evaluation for the presence of genetic mutations of coagulation factors V and II.