Syncytiotrophoblast microvesicles released from pre-eclampsia placentae exhibit increased tissue factor activity.
BACKGROUND
Pre-eclampsia is a complication of pregnancy associated with activation of coagulation. It is caused by the placenta, which sheds increased amounts of syncytiotrophoblast microvesicles (STBM) into the maternal circulation. We hypothesized that STBM could contribute to the haemostatic activation observed in pre-eclampsia.


RESULTS
STBM were collected by perfusion of the maternal side of placentae from healthy pregnant women and women with pre-eclampsia at caesarean section. Calibrated automated thrombography was used to assess thrombin generation triggered by STBM-borne tissue factor in platelet poor plasma (PPP). No thrombin was detected in PPP alone but the addition of STBM initiated thrombin generation in 14/16 cases. Pre-eclampsia STBM significantly shortened the lag time (LagT, P = 0.01) and time to peak thrombin generation (TTP, P = 0.005) when compared to normal STBM. Blockade of tissue factor eliminated thrombin generation, while inhibition of tissue factor pathway inhibitor significantly shortened LagT (p = 0.01) and TTP (P<0.0001), with a concomitant increase in endogenous thrombin potential.


CONCLUSIONS
STBM triggered thrombin generation in normal plasma in a tissue factor dependent manner, indicating that TF activity is expressed by STBM. This is more pronounced in STBM shed from pre-eclampsia placentae. As more STBM are shed in pre-eclampsia these observations give insight into the disordered haemostasis observed in this condition.
Nuffield Department of Obstetrics and Gynaecology, University of Oxford, Level 3, Women's Centre, John Radcliffe Hospital, Oxford, United Kingdom. chris.gardiner@obs-gyn.ox.ac.uk
Chris
C
Gardiner
Dionne S
DS
Tannetta
Carol A
CA
Simms
Paul
P
Harrison
Christopher W G
CW
Redman
Ian L
IL
Sargent
D000328:Adult; D005260:Female; D006801:Humans; D011225:Pre-Eclampsia / Q000097:blood / Q000378:metabolism* / Q000473:pathology; D011247:Pregnancy; D011994:Recombinant Proteins / Q000494:pharmacology; D013917:Thrombin / Q000378:metabolism; D013925:Thromboplastin / Q000378:metabolism*; D014327:Trophoblasts / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology
D011994:Recombinant Proteins; D013925:Thromboplastin; D013917:Thrombin