title: Amniotic fluid contains tissue factor, a potent initiator of coagulation.
abstract: A primary clinical manifestation of amniotic fluid embolism is coagulopathy. Prior studies have identified a poorly characterized yet potent procoagulant property in amniotic fluid that increases with gestational age. One possible source of procoagulant activity is tissue factor, a primary biologic initiator of coagulation. We used sensitive immunoassays and functional assays to identify substantial quantities of tissue factor antigen and tissue factor-specific procoagulant activity in amniotic fluid, which increased with gestational age. Moreover, tissue factor accounted for virtually all of the coagulant potential of amniotic fluid. Amniotic tissue factor appeared intact and membrane bound and, when reconstituted into synthetic microvesicles of optimal phospholipid content, displayed nearly full activity. Calcium chelation and sonication experiments suggested that the presence of inhibitors and the physical configuration of membrane-bound tissue factor in amniotic fluid might explain the modest reduction in tissue factor procoagulant activity relative to total antigen levels observed in vivo. We postulate that the substantial quantities of functionally active tissue factor in amniotic fluid account for the coagulation changes accompanying amniotic fluid embolism and could indirectly contribute to the characteristic hemodynamic derangements of amniotic fluid embolism.
authors.affiliation: Department of Obstetrics, Gynecology and Reproductive Science, Mount Sinai School of Medicine, New York, NY 10029-6574.
authors.forename: C J
authors.initials: CJ
authors.lastname: Lockwood
authors.forename: R
authors.initials: R
authors.lastname: Bach
authors.forename: A
authors.initials: A
authors.lastname: Guha
authors.forename: X D
authors.initials: XD
authors.lastname: Zhou
authors.forename: W A
authors.initials: WA
authors.lastname: Miller
authors.forename: Y
authors.initials: Y
authors.lastname: Nemerson
mesh_terms: D000650:Amnion / Q000737:chemistry; D000653:Amniotic Fluid / Q000737:chemistry*; D015153:Blotting, Western; D004619:Embolism, Amniotic Fluid / Q000503:physiopathology; D004797:Enzyme-Linked Immunosorbent Assay; D005167:Factor VII / Q000032:analysis / Q000037:antagonists & inhibitors; D015951:Factor Xa / Q000032:analysis; D005260:Female; D006801:Humans; D008074:Lipoproteins / Q000032:analysis; D010743:Phospholipids / Q000032:analysis; D011247:Pregnancy; D011480:Protease Inhibitors / Q000032:analysis; D011516:Prothrombin / Q000032:analysis; D011517:Prothrombin Time; D013010:Sonication; D013925:Thromboplastin / Q000032:analysis* / Q000037:antagonists & inhibitors; D014461:Ultracentrifugation
chemical_list: D008074:Lipoproteins; D010743:Phospholipids; D011480:Protease Inhibitors; C051928:lipoprotein-associated coagulation inhibitor; D005167:Factor VII; D011516:Prothrombin; C025337:Factor IIa; D013925:Thromboplastin; D015951:Factor Xa