טכניון מכון טכנולוגי לישראל
הטכניון מכון טכנולוגי לישראל - בית הספר ללימודי מוסמכים  
M.Sc Thesis
M.Sc StudentKatzenell Sarah
SubjectMicroparticles Involvement in Gestational Vascular
Complications Characterized by Excess
Coagulability
DepartmentDepartment of Medicine
Supervisors Professor Benjamin Brenner
Assistant Professor Anat Aharon
Full Thesis textFull thesis text - English Version


Abstract

Introduction: Pregnancy is a state of increased coagulability. Some gestational vascular complications (GVC), such as preeclampsia, are associated with further increases in coagulability, increased risk of maternal thrombotic events, placental pathology and adverse pregnancy outcome. Tissue factor (TF, the main initiator of the clotting cascade) and tissue factor pathway inhibitor (TFPI) have been implicated in the etiology of GVC. Microparticles (MPs) are membrane vesicles which bud from apoptotic or activated cells. MPs may carry TF, and are known to contribute to clot formation. Study Aims: We hypothesized that MPs contribute to gestational coagulation, and are involved in the progression of GVC. Our aim was to characterize MPs from healthy and GVC pregnancies in several aspects: cellular origin, coagulation potential, angiogenic potential, and their effects on endothelial and placental trophoblast coagulation potential. Results: We found that GVC is characterized by changes in the MPs cellular origin which indicate vascular damage. Furthermore, MPs from GVC pregnancies have a perturbed balance of TF and TFPI both on their surface and in their “cytosol”. Surprisingly, MPs from healthy non-pregnant women had a TF-mitigating effect on endothelial cells. MPs from healthy pregnancies had a similar effect on placental trophoblasts. This effect may be part of the MPs role in healthy physiology. Lastly, we found that MPs from GVC induced significantly more trophoblast apoptosis than did MPs from healthy pregnancies. Conclusions: We conclude that MPs both reflect and affect the hemostatic balance in healthy pregnancies and in GVC. MPs contribute to the excess coagulability which characterizes GVC, and may exacerbate its progression by causing placental trophoblast damage.