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

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 (AF)-tissue factor concentration and activity, as well as the concentrations of thrombin-antithrombin 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 AF-TF 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 AF-TAT 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.

• Authors: 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
• Journal: The journal of maternal-fetal & neonatal medicine : the official journal of the European Association of Perinatal Medicine, the Federation of Asia and Oceania Perinatal Societies, the International Society of Perinatal Obstetricians (J Matern Fetal Neonatal Med) Vol. 22 Issue 8 Pg. 672-87 (Aug 2009) ISSN: 1476-4954 [Electronic] England
• PMID: 19736615 (Publication Type: Journal Article, Research Support, N.I.H., Intramural)

Chemical References

• Lipoproteins
• Peptide Fragments
• Protein Precursors
• antithrombin III-protease complex
• lipoprotein-associated coagulation inhibitor
• CD40 Ligand
• prothrombin fragment 1
• prothrombin fragment 2
• Antithrombin III
• Prothrombin
• Thromboplastin
• Peptide Hydrolases
• Thrombin

Topics

• Adult
• Amniotic Fluid (chemistry)
• Antithrombin III (analysis)
• CD40 Ligand (blood)
• Cross-Sectional Studies
• Female
• Fetal Death (blood)
• Humans
• Lipoproteins (blood)
• Peptide Fragments (blood)
• Peptide Hydrolases (analysis)
• Platelet Activation
• Pre-Eclampsia (blood)
• Pregnancy
• Protein Precursors (blood)
• Prothrombin
• Thrombin (analysis)
• Thromboplastin (analysis, physiology)