Evidence of maternal platelet activation, excessive thrombin generation, and high amniotic fluid tissue factor immunoreactivity and functional activity in patients with fetal death

Offer Erez*, Francesca Gotsch, Shali Mazaki-Tovi, Edi Vaisbuch, Juan Pedro Kusanovic, Chong Jai Kim, Tinnakorn Chaiworapongsa, Deborah Hoppensteadt, Jawed Fareed, Nandor G. Than, Chia Ling Nhan-Chang, Lami Yeo, Percy Pacora, Moshe Mazor, Sonia S. Hassan, Pooja Mittal, Roberto Romero

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

Abstract

Objective. Fetal death can lead to disseminated intravascular coagulation or fetal death syndrome. However, currently it is not clear what are the changes in the coagulation system in patients with a fetal death without the fetal death syndrome. This study was undertaken to determine: 1 whether fetal death in the absence of fetal death syndrome is associated with changes in hemostatic markers in maternal plasma and amniotic fluid; and 2 whether maternal hypertension or placental abruption are associated with further changes in the hemostatic profile of these patients. Methods. A cross-sectional study included the following: 1 determination of changes in markers of coagulation and platelet activation in patients with a normal pregnancy n 71 and patients with fetal demise FD without disseminated intravascular coagulation n 65; 2 determination of the amniotic fluid AFtissue factor concentration and activity, as well as the concentrations of thrombinantithrombin III TAT complexes in patients with a normal pregnancy n 25 and those with a FD n 36 who underwent amniocentesis. Plasma and AF concentrations of TAT complexes and TF an index of thrombin generation, as well as maternal plasma concentrations of sCD40L a marker of platelet activation, tissue factor pathway inhibitor TFPI and prothrombin fragments PF 1 2 also an indicator of in vivo thrombin generation were measured by ELISA. TF and TFPI activity were measured using chromogenic assays. Results. 1 patients with FD without hypertension had a higher median maternal plasma sCD40L concentration than normal pregnant women P < 0.001; 2 patients with FD had a higher median maternal plasma TAT III complexes than women with a normal pregnancy P < 0.001; 3 the median AFTF concentration and activity were higher in the FD group than in the normal pregnancy group P < 0.001 for both; 4 patients with preeclampsia and FD had a higher median maternal plasma immunoreactive TF concentration than both normotensive patients with FD and women with normal pregnancies P < 0.001 and P 0.001, respectively; 5 the median plasma TF activity was higher in patients with preeclampsia and FD than that of women with normal pregnancies P 0.003; 6 among patients with a FD, those with placental abruption had a higher median AFTAT complexes concentration than those without abruption P 0.0004. Conclusions. Our findings indicate that: 1 mothers with a FD have evidence of increased in vivo thrombin generation and platelet activation than women with normal pregnancies; 2 patients with a FD and hypertension had a higher degree of TF activation than those with fetal death but without hypertension; 3 the AF of women with a FD had a higher median TF concentration and activity than that of normal pregnant women. AF can be a potential source for tissue factor and it participates in the development of fetal death syndrome in patients with a retained dead fetus.

Original languageEnglish
Pages (from-to)672-687
Number of pages16
JournalJournal of Maternal-Fetal and Neonatal Medicine
Volume22
Issue number8
DOIs
StatePublished - 2009
Externally publishedYes

Funding

FundersFunder number
National Institutes of Health
U.S. Department of Health and Human Services
Eunice Kennedy Shriver National Institute of Child Health and Human Development

    Keywords

    • Abruption
    • Preeclampsia
    • Pregnancy
    • Prothrombin fragments 1 2
    • Soluble CD40L
    • Thrombinantithrombin complexes

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