Download PDF
Semin Thromb Hemost 2011; 37(2): 165-174
DOI: 10.1055/s-0030-1270345
© Thieme Medical Publishers

Coagulation and Fibrinolysis in Amniotic Fluid: Physiology and Observations on Amniotic Fluid Embolism, Preterm Fetal Membrane Rupture, and Pre-Eclampsia

Mieczysław Uszyński1 , Waldemar Uszyński2
  • 1Department of Propedeutics of Medicine, Collegium Medicum in Bydgoszcz, Nicolaus Copernicus University in Toruń, Poland
  • 2Regional Hospital in Włocławek, Poland
Further Information

Publication History

Publication Date:
02 March 2011 (online)

    Permissions and Reprints

ABSTRACT

Two dangerous obstetric complications, amniotic fluid embolism and preterm prelabor rupture of membranes (PROM), can be caused by amniotic fluid (AF) constituents. Disseminated intravascular coagulation (DIC) is related to the former complication, whereas local thrombin/plasmin-dependent collagenolysis in the decidua and fetal membranes is associated with the latter. In AF, most proteins of the coagulation and fibrinolysis system, known as plasma constituents, have been identified based on the activity and/or presence of antigen. The AF levels of most of these proteins are low (< 2 to 5% of the respective maternal plasma levels). However, there are some exceptions: tissue factor (TF), urokinase plasminogen activator (uPA) and its receptor (uPAR), as well as plasminogen activator inhibitors. The AF level of fetal fibrinogen is trace, which is a particular exception. The key enzymes of coagulation and fibrinolysis, thrombin and plasmin, are generated in AF. Thrombin generation is four- to fivefold higher than in maternal plasma as measured by the concentration of the prothrombin fragments 1 + 2 (F 1 + 2) and thrombin-antithrombin complexes, whereas plasmin generation is relatively low as measured by the plasmin–α-2-antiplasmin complexes. Phosphatidylserine, a phospholipid, and thrombin-activatable fibrinolysis inhibitor (TAFI) are novel components of AF. Phosphatidylserine contributes to DIC in AF embolism; TAFI is considered a link between coagulation and fibrinolysis. uPA and uPAR are the factors contributing to PROM via plasmin-dependent proteolysis. Intriguing is the assumption that TF and its inhibitor can be risk factors for PROM through thrombin-dependent activation of matrix prometalloproteinases in the decidua and fetal membranes. It is unknown whether the amniotic pool of hemostatic components is involved in pre-eclampsia pathogenesis.

KEYWORDS

Amniotic fluid - procoagulants - anticoagulants - fibrinolysis - PROM

REFERENCES

  • 1 Albrechtsen O K, Trolle D. A fibrinolytic system in human amniotic fluid.  Acta Haematol. 1955;  14 (6) 376-382
    CrossrefPubMedGoogle Scholar
  • 2 Uszyński M, Maciejewski K, Uszyński W, Kuczyński J. Placenta and myometrium—the two main sources of fibrinolytic components during pregnancy.  Gynecol Obstet Invest. 2001;  52 (3) 189-193
    CrossrefPubMedGoogle Scholar
  • 3 Lockwood C J, Krikun G, Rahman M, Caze R, Buchwalder L, Schatz F. The role of decidualization in regulating endometrial hemostasis during the menstrual cycle, gestation, and in pathological states.  Semin Thromb Hemost. 2007;  33 (1) 111-117
    Article in Thieme ConnectPubMedGoogle Scholar
  • 4 Watanabe T, Araki M, Mimuro J, Tamada T, Sakata Y. Fibrinolytic components in fetal membranes and amniotic fluid.  Am J Obstet Gynecol. 1993;  168 (4) 1283-1289
    PubMedGoogle Scholar
  • 5 Gulbis B, Jauniaux E, Jurkovic D, Thiry P, Campbell S, Ooms H A. Determination of protein pattern in embryonic cavities of human early pregnancies: a means to understand materno-embryonic exchanges.  Hum Reprod. 1992;  7 (6) 886-889
    PubMedGoogle Scholar
  • 6 Michel P E, Crettaz D, Morier P et al. Proteome analysis of human plasma and amniotic fluid by Off-Gel isoelectric focusing followed by nano-LC-MS/MS.  Electrophoresis. 2006;  27 (5–6) 1169-1181
    CrossrefPubMedGoogle Scholar
  • 7 Mavrou A, Anagnostopoulos A K, Kolialexi A et al. Proteomic analysis of amniotic fluid in pregnancies with Turner syndrome fetuses.  J Proteome Res. 2008;  7 (5) 1862-1866
    CrossrefPubMedGoogle Scholar
  • 8 Tisi D K, Emard J J, Koski K G. Total protein concentration in human amniotic fluid is negatively associated with infant birth weight.  J Nutr. 2004;  134 (7) 1754-1758
    PubMedGoogle Scholar
  • 9 Cade J F, Hirsh J, Martin M. Placental barrier to coagulation factors: its relevance to the coagulation defect at birth and to haemorrhage in the newborn.  BMJ. 1969;  2 (5652) 281-283
    CrossrefPubMedGoogle Scholar
  • 10 Brace R A. Physiology of amniotic fluid volume regulation. In: Rao K A, Ross M G, eds. Amniotic Fluid. Bangalore, India: Prism Books; 1999: 110-132
    Google Scholar
  • 11 Köttgen E, Hell B, Müller C, Tauber R. Demonstration of glycosylation variants of human fibrinogen, using the new technique of glycoprotein lectin immunosorbent assay (GLIA).  Biol Chem Hoppe Seyler. 1988;  369 (10) 1157-1166
    CrossrefPubMedGoogle Scholar
  • 12 Kimball M E, Milunsky A, Giannusa P, Carvalho A C. Amniotic fluid fibrinogen degradation products in the prenatal diagnosis of neural tube defects.  Am J Obstet Gynecol. 1977;  128 (3) 294-299
    PubMedGoogle Scholar
  • 13 Lockwood C J, Bach R, Guha A, Zhou X D, Miller W A, Nemerson Y. Amniotic fluid contains tissue factor, a potent initiator of coagulation.  Am J Obstet Gynecol. 1991;  165 (5 Pt 1) 1335-1341
    PubMedGoogle Scholar
  • 14 Erez O, Gotsch F, Mazaki-Tovi S et al. Evidence of maternal platelet activation, excessive thrombin generation, and high amniotic fluid tissue factor immunoreactivity and functional activity in patients with fetal death.  J Matern Fetal Neonatal Med. 2009;  22 (8) 672-687
    CrossrefPubMedGoogle Scholar
  • 15 Uszyński M, Żekanowska E, Uszyński W, Kuczyński J. Tissue factor (TF) and tissue factor pathway inhibitor (TFPI) in amniotic fluid and blood plasma: implications for the mechanism of amniotic fluid embolism.  Eur J Obstet Gynecol Reprod Biol. 2001;  95 (2) 163-166
    CrossrefPubMedGoogle Scholar
  • 16 González-Quintero V H, Jiménez J J, Jy W et al. Elevated plasma endothelial microparticles in preeclampsia.  Am J Obstet Gynecol. 2003;  189 (2) 589-593
    CrossrefPubMedGoogle Scholar
  • 17 Thompson A R. Factor IX and prothrombin in amniotic fluid and fetal plasma: constraints on prenatal diagnosis of hemophilia B and evidence of proteolysis.  Blood. 1984;  64 (4) 867-874
    PubMedGoogle Scholar
  • 18 Ludwig H, Metzger H. Das uterine Placentarbett post partum in Rasterelektronenmikroskop, zugleich ein Beitrag zur Frage der extravasalen Fibrinbildung.  Arch Gynakol. 1971;  210 251-266
    CrossrefPubMedGoogle Scholar
  • 19 McVey J H. Tissue factor pathway.  Baillieres Clin Haematol. 1999;  12 361-372
    PubMedGoogle Scholar
  • 20 Zhou J, Liu S, Ma M et al. Procoagulant activity and phosphatidylserine of amniotic fluid cells.  Thromb Haemost. 2009;  101 (5) 845-851
    PubMedGoogle Scholar
  • 21 Steiner P E, Lushbaugh C C. Maternal pulmonary embolism by amniotic fluid as a cause of obstetric shock and unexpected deaths in obstetrics.  JAMA. 1941;  117 1245-1254
    CrossrefPubMedGoogle Scholar
  • 22 Uszyński W, Uszyński M, Zekanowska E. Thrombin markers in pregnant women: measurements of prothrombin fragments F 1 + 2 and thrombin-antithrombin III complexes (TAT) in the cord blood, the mother's blood and in amniotic fluid.  [in Polish] Ginekol Pol. 2004;  75 (8) 595-602
    PubMedGoogle Scholar
  • 23 Uszyński M, Zekanowska E, Kotzbach M, Uszyński W, Kotzbach R. Protein C, protein S, and thrombomodulin in amniotic fluid. A preliminary study.  J Perinat Med. 2006;  34 (4) 289-292
    CrossrefPubMedGoogle Scholar
  • 24 Uszyński W, Zekanowska E, Uszyński M, Rystok D. Concentration of annezin in gestational tissues: placenta, fetal membranes, myometrium, and amniotic fluid.  [in Polish] Gin Pol. 2006;  77 603-610
    PubMedGoogle Scholar
  • 25 Uszyński M, Kłyszejko A, Zekanowska E. Plasminogen, α(2)-antiplasmin and complexes of plasmin-α(2)-antiplasmin (PAP) in amniotic fluid and blood plasma of parturient women.  Eur J Obstet Gynecol Reprod Biol. 2000;  93 (2) 167-171
    CrossrefPubMedGoogle Scholar
  • 26 Uszyński M, Perlik M, Uszyński W, Zekanowska E. Urokinase plasminogen activator (uPA) and its receptor (uPAR) in gestational tissues; measurements and clinical implications.  Eur J Obstet Gynecol Reprod Biol. 2004;  114 (1) 54-58
    CrossrefPubMedGoogle Scholar
  • 27 Hajjar K A. Cellular receptors in the regulation of plasmin generation.  Thromb Haemost. 1995;  74 (1) 294-301
    PubMedGoogle Scholar
  • 28 Uszyński W, Uszyński M, Zekanowska E. Thrombin activatable fibrinolysis inhibitor (TAFI) in human amniotic fluid. A preliminary study.  Thromb Res. 2007;  119 (2) 241-245
    CrossrefPubMedGoogle Scholar
  • 29 Nesheim M, Wang W, Boffa M, Nagashima M, Morser J, Bajzar L. Thrombin, thrombomodulin and TAFI in the molecular link between coagulation and fibrinolysis.  Thromb Haemost. 1997;  78 (1) 386-391
    PubMedGoogle Scholar
  • 30 Wang W, Boffa M B, Bajzar L, Walker J B, Nesheim M E. A study of the mechanism of fibrynolysis by activated thrombin-activatable inhibitor.  J Biol Chem. 1998;  273 27176-27181
    CrossrefPubMedGoogle Scholar
  • 31 Gris J C, Neveu S, Tailland M L, Courtieu C, Marès P, Schved J F. Use of a low-molecular weight heparin (enoxaparin) or of a phenformin-like substance (moroxydine chloride) in primary early recurrent aborters with an impaired fibrinolytic capacity.  Thromb Haemost. 1995;  73 (3) 362-367
    PubMedGoogle Scholar
  • 32 Vassalli J D. The urokinase receptor.  Fibrinolysis. 1994;  8 172-181
    PubMedGoogle Scholar
  • 33 Vadillo-Ortega F, Hernandez A, Gonzalez-Avila G, Bermejo L, Iwata K, Strauss III JF. Increased matrix metalloproteinase activity and reduced tissue inhibitor of metalloproteinases-1 levels in amniotic fluids from pregnancies complicated by premature rupture of membranes.  Am J Obstet Gynecol. 1996;  174 (4) 1371-1376
    CrossrefPubMedGoogle Scholar
  • 34 Lijnen H R. Plasmin and matrix metalloproteinases in vascular remodeling.  Thromb Haemost. 2001;  86 (1) 324-333
    Article in Thieme ConnectPubMedGoogle Scholar
  • 35 Erez O, Espinoza J, Chaiworapongsa T et al. A link between a hemostatic disorder and preterm PROM: a role for tissue factor and tissue factor pathway inhibitor.  J Matern Fetal Neonatal Med. 2008;  21 (10) 732-744
    CrossrefPubMedGoogle Scholar
  • 36 Stephenson C D, Lockwood C J, Ma Y, Guller S. Thrombin-dependent regulation of matrix metalloproteinase (MMP)-9 levels in human fetal membranes.  J Matern Fetal Neonatal Med. 2005;  18 (1) 17-22
    CrossrefPubMedGoogle Scholar
  • 37 Adachi T, Nakabayashi M, Sakwra M, Ando K. Involvement of fibrinolytic factors in mid trimester amniotic fluid with development of severe early-onset preeclampsia.  Semin Thromb Hemost. 1999;  25 (5) 447-450
    Article in Thieme ConnectPubMedGoogle Scholar
  • 38 Tanjung M, Siddik H Z, Hariman H et al.. Coagulation and fibrinolysis in preeclampsia and neometes.  Clin Appl Thromb/Hemost. 2005;  11 (4) 467-473
    CrossrefPubMedGoogle Scholar
  • 39 Hathaway W, Corrigan J. Report of Scientific and Standardization Subcommitee on Neonatal Hemostasis.  Thromb Haemost. 1991;  65 323-325
    PubMedGoogle Scholar

Mieczysław UszyńskiM.D. 

Professor, Department of Propedeutics of Medicine, Collegium Medicum in Bydgoszcz

Nicolaus Copernicus University in Toruń, Poland

Email: kizproped@amb.bydgoszcz.pl

      >