Adverse effects of lupus anticoagulant positive blood sera on placental viability can be prevented by heparin in vitro

Objective: Lupus anticoagulant poses a significant risk factor for obstetric complications, whereas heparin improves live birth rates in those pregnancies. Pathophysiology of antiphospholipid antibodies on placental function involves coagulopathies and thrombosis but also dysregulated trophoblast turnover. Study design: With the use of placental explant cultures, we assessed the effect of lupus anticoagulant positive sera (LA(+) sera) on apoptosis, mitosis, and invasion of trophoblast and determined the role of unfractionated heparin in regulating these functions. Results: LA(+) sera were associated with increased placental apoptosis (TUNEL, M30 formation, DNA laddering). LA(+) sera decreased villous trophoblast proliferation and reduced extravillous trophoblast invasion through matrigel. Heparin attenuated LA(+) sera-induced apoptosis and facilitated trophoblast invasion. Conclusion: Lupus anticoagulant may impair placentation by increasing apoptosis, attenuating mitosis and reducing invasion of the trophoblast. The direct effects on trophoblast viability by heparin demonstrate an alternative biologic function for this anticoagulant and raise the possibility that anomalous trophoblast development may be therapeutically regulated. (C) 2004 Elsevier Inc. All rights reserved.