טכניון מכון טכנולוגי לישראל
הטכניון מכון טכנולוגי לישראל - בית הספר ללימודי מוסמכים  
Ph.D Thesis
Ph.D StudentAharon Anat
SubjectProcoagulant and Anticoagulant Mechanisms in Human Placenta
DepartmentDepartment of Medicine
Supervisor Professor Benjamin Brenner


Abstract

PROCOAGULANT AND ANTICOAGULANT MECHANISMS IN HUMAN PLACENTA


Abstract

The placenta is a highly vascularized organ with unique blood supply from both fetal and maternal circulation. Local placental haemostatic mechanisms maintain blood fluidity through balance between activators and inhibitors, which may be disturbed by physiological stimuli such as inflammation.

Aims of research

1.         Evaluating the local procoagulant and anticoagulant proteins  (TF, TFPI, TFPI-2, TM, EPCR) in human placenta.

2.         Establishing an in-vitro model of primary trophoblast cultures and characterize their cellular procoagulant / anticoagulant properties.

3.         Determine the effect of inflammatory cytokines as a model of stress in pregnancy on trophoblasts as compared to endothelial cells (HUVEC).

Results:

Human placenta: TFPI level (protein and mRNA) was significantly low in women with gestational vascular complications (GVC). TFPI level in thrombophilic women with previous Pregnancy loss (PL) that were treated with low molecular weight heparin (LMWH) was comparable to healthy women, indicating possible effect of therapy. No significant difference in levels of TF, TM and EPCR was documented.

Cell culture: Primary cell cultures of syncytiotrophoblasts were established and characterized by vascular and hormonal markers. High level of TF was demonstrated in trophoblasts as compared to the low level in HUVEC. Nevertheless, low level of TFPI in trophoblasts was demonstrated as compared to high TFPI level in HUVEC, pointing to the prothrombotic character of trophoblasts. EPCR was first demonstrated in trophoblasts. The trhophoblasts in culture respond to inflammation stimuli of cytokines IL1a, TNFa and the LPS, which intensify their procoagulant character.  

Conclusions

Human placentae express local haemostatic proteins. Trophoblasts are procoagulant and HUVEC are anticoagulant by nature. This haemostatic balance may be critical for placenta function. The balance of procoagulant and anticoagulant proteins in the placenta may determine gestational outcome, and the antithrombotic treatment (LMWH) can modulate the haemostatic balance, and improve gestational outcome.