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.


METHODS
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.


CONCLUSIONS
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.
Bose
Patrick
P
Department of Anatomy, University Hospital, Aachen, Germany.
Black
Simon
S
Kadyrov
Mamed
M
Bartz
Clemens
C
Shlebak
Abdul
A
Regan
Lesley
L
Huppertz
Berthold
B
D000022:Abortion, Spontaneous; D000328:Adult; D017152:Antibodies, Antiphospholipid / Q000276:immunology*; D017209:Apoptosis / Q000187:drug effects / Q000502:physiology*; D015153:Blotting, Western; D053938:DNA Fragmentation; D005260:Female; D006493:Heparin / Q000494:pharmacology*; D006801:Humans; D007150:Immunohistochemistry; D020287:In Situ Nick-End Labeling; D008180:Lupus Erythematosus, Systemic / Q000097:blood* / Q000276:immunology; D008875:Middle Aged; D008938:Mitosis / Q000502:physiology; D010920:Placenta / Q000166:cytology / Q000187:drug effects; D011247:Pregnancy; D011261:Pregnancy Trimester, First; D012016:Reference Values; D012680:Sensitivity and Specificity; D046509:Tissue Culture Techniques; D014327:Trophoblasts / Q000187:drug effects* / Q000276:immunology
D017152:Antibodies, Antiphospholipid; D006493:Heparin