Syncytiotrophoblast Microvesicles Released from Pre-Eclampsia Placentae Exhibit Increased Tissue Factor Activity

被引:71
作者
Gardiner, Chris [1 ]
Tannetta, Dionne S. [1 ]
Simms, Carol A. [1 ]
Harrison, Paul [2 ]
Redman, Christopher W. G. [1 ]
Sargent, Ian L. [1 ]
机构
[1] Univ Oxford, John Radcliffe Hosp, Nuffield Dept Obstet & Gynaecol, Womens Ctr, Oxford OX3 9DU, England
[2] Churchill Hosp, Oxford Haemophilia & Thrombosis Ctr, Oxford OX3 7LJ, England
来源
PLOS ONE | 2011年 / 6卷 / 10期
基金
英国惠康基金;
关键词
AUTOMATED THROMBIN GENERATION; FACTOR PATHWAY INHIBITOR; HORMONE MESSENGER-RNA; NORMAL-PREGNANCY; TROPHOBLAST CELLS; FIBRINOPEPTIDE-A; MATERNAL PLASMA; PRE-ECLAMPSIA; WHOLE-BLOOD; MICROPARTICLES;
D O I
10.1371/journal.pone.0026313
中图分类号
O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];
学科分类号
07 ; 0710 ; 09 ;
摘要
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. Methodology/Principal Findings: 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/Significance: 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.
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页数:7
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