Procoagulant extracellular vesicles in amniotic fluid.

Abstract

Embolization of amniotic fluid (AF) into the blood circulation leads to disseminated intravascular coagulation (DIC). Procoagulant phosphatidylserine (PS)- and tissue factor (TF)-exposing extracellular vesicles (EVs) might play an important role in AF embolism-induced DIC. It was the aim of the present study to perform analyses of the procoagulant properties of AF with a panel of functional coagulation assays and flow cytometry. We applied a prothrombinase assay (that quantifies PS exposure on EVs), an EV-associated TF activity assay, a fibrin generation assay, a thrombin generation assay, a whole blood clotting model, and flow cytometry in AF and control plasma. We found that PS exposure on EVs was 21-fold increased in AF compared with plasma. Also, EV-associated TF activity was highly increased in AF compared with plasma. AF-derived EVs activated the blood coagulation cascade via PS and TF in the fibrin and thrombin generation assays. In a whole blood clotting model, AF-derived EVs significantly shortened the clotting time from 734 ± 139 seconds in the presence to 232 ± 139 seconds in the absence of an anti-TF antibody. The contact activation pathway via factor XII (FXII) was not affected. Applying flow cytometry, a subpopulation of PS+ and TF+ EVs was identified in AF but not in control plasma. In conclusion, we investigated the effect of AF on blood coagulation and found that PS+ and TF+ EVs determine their procoagulant potential. Taken together, our data further delineate the pathomechanisms underlying AF-induced coagulopathy.

• Authors: Lena Hell, Lukas Wisgrill, Cihan Ay, Andreas Spittler, Michael Schwameis, Bernd Jilma, Ingrid Pabinger, Peter Altevogt, Johannes Thaler
• Journal: Translational research : the journal of laboratory and clinical medicine (Transl Res) Vol. 184 Pg. 12-20.e1 (06 2017) ISSN: 1878-1810 [Electronic] United States
• PMID: 28236427 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2017 Elsevier Inc. All rights reserved.

Chemical References

• Phosphatidylserines
• Fibrin
• Thromboplastin
• Thrombin

Topics

• Amniotic Fluid (cytology, metabolism)
• Disseminated Intravascular Coagulation (blood, pathology)
• Embolism, Amniotic Fluid (pathology)
• Extracellular Vesicles
• Female
• Fibrin (metabolism)
• Flow Cytometry
• Humans
• Phosphatidylserines (metabolism)
• Pregnancy
• Thrombin (metabolism)
• Thromboplastin (metabolism)
• Thrombosis