RESUMO
INTRODUCTION: Classical reference data concerning the coagulation system and fibrinolysis in fetuses and newborns date back to the 1990 s. Since that time a number of methodological or other improvements have been implemented, which may cast some doubt on timeliness of the data. The study objective was to measure the levels of Contact Activation System (CAS) components by antigen, i.e. factors XII and XI (FXII, FXI), prekallikrein (PK) and high molecular weight kininogen (HMWK) in cord blood and maternal blood. MATERIAL AND METHODS: The study group consisted of 35 healthy parturient women with an uneventful pregnancy and birth. The samples of cord blood and maternal blood were obtained immediately after delivery, before clumping the umbilical cord. The CAS components were measured by immunoenzymatic method (ELISA). RESULTS: The median concentrations of CAS components in cord blood plasma and mother's plasma were as follow: FXII: 1.02 (0.60- 2.58) ng/mg protein vs. 0.94 (0.66-1.86) ng/mg protein (p>0.05); FXI: 2.71(0.03-8.0) ng/mg protein vs. 0.92 (0.03-10.44) ng/mg protein (p>0.05); PK: 168.78 (104.28-261.16) pg/mg protein vs. 113.44 (79.94-146.70) pg/mg protein (p>0.05); HMWK: 2169.45 (1530.64- 2539.83) ng/mg protein vs. 2857.96 (2541.52-3161.04) ng/mg protein (p<0.001). CONCLUSIONS: 1. The antigen levels of the three contact factors, i.e. FXII, FXI and PK in the cord blood of full-term and healthy fetuses were similar to those observed in mother's blood immediately after delivery. Only high molecular weight kininogen was found to be lower (accounting for 84% of the values noted in mothers). 2. Based on our measurements, we claim that the cited reference data concerning the contact factors in full-term and healthy newborns are underestimated; hence, new reference values need to be determined for each antigen and activity contact factor level.
Assuntos
Sangue Fetal/metabolismo , Gravidez/sangue , Adulto , Feminino , Sangue Fetal/citologia , Humanos , Projetos Piloto , Adulto JovemRESUMO
BACKGROUND/AIM: It is believed that the amniotic fluid-derived TF, in the case of amniotic fluid embolism (AFE), contributes to acute disseminated intravascular coagulation (DIC) and obstetric shock in the mother. However, the role of amniotic fluid-derived contact phase coagulation factors that irrupt into the bloodstream simultaneously with TF is still unknown. Our study objective was to identify and measure the concentrations of CAS components and TF in amniotic fluid. MATERIAL AND METHODS: The study group consisted of 30 healthy parturients with uneventful pregnancy and birth. Amniotic fluid (AF) and maternal blood were sampled at the end of the first stage of labor. The components of ACS, i.e. factors XII and XI (FXII, FXI), prekallikrein (PK), high molecular weight kininogen (HMWK), and tissue factor (TF) were measured by immunoenzymatic method (ELISA). RESULTS: All ACS components were detected in AF; their levels were higher in AF than in the maternal plasma: FXII--29.17 ng/mg protein vs. 0.94 ng/mg protein (medians); FXI--27.28 ng/mg protein vs. 0.92 ng/mg protein (medians); PK--88442.04 ng/mg protein vs. 113.44 ng/mg protein (medians); HMWK--4253.82 ng/mg protein vs. 2857.96 ng/mg protein (medians). The concentration of TF in amniotic fluid was 39.46 pg/mg protein (median) vs. 0.41 pg/mg protein (median) in blood plasma. CONCLUSIONS: 1.The ACS components, i.e. FXII, FXI, PK and HMWK, are the constituents of amniotic fluid. 2.The concentrations of the amniotic fluid-derived factors having a coagulation initiation potential, i.e. TF and contact phase coagulation factors, are higher in amniotic fluid than in mother's blood plasma.
Assuntos
Coagulação Sanguínea/fisiologia , Embolia Amniótica/fisiopatologia , Adulto , Ativação Enzimática , Feminino , Humanos , GravidezRESUMO
INTRODUCTION: Microparticles (MPs) are submicron fragments of the cell membrane affecting many biological processes, e.g. coagulation. The aim of the study was to determine (i) MPs and (ii) tissue factor bearing MPs (MPs-TF) in the amniotic fluid and in blood plasma of parturient women, as well as to assess (iii) TF and TFPI. MATERIAL AND METHODS: The study group consisted of 38 women laboring at term, whereas the control group included 20 non-pregnant women. ELISA method was used to evaluate MPs, MPs-TF, TF and TFPI. RESULTS: The levels of MPs and MPs-TF were significantly higher in the amniotic fluid than in blood plasma of parturient women: the level of MPs was 41.08 times higher (medians: 246.48 nM PS vs. 6.00 nM PS, respectively, p<0.001), and the level of MPs-TF was 18.59 times higher (medians: 90.16pg/ml vs. 4.85pg/ml, respectively) (p<0.001). CONCLUSIONS: 1. Microparticles (MPs) and tissue factor-bearing MPs (MPs-TF) are constituent components of amniotic fluid. 2. It is reasonable to assume that these components together with tissue factor (TF) and its inhibitor (TFPI) can participate in life-threatening coagulation disturbances in amniotic fluid embolism, and to take into consideration their impact on fetal development.
Assuntos
Líquido Amniótico/química , Micropartículas Derivadas de Células/química , Tromboplastina/análise , Líquido Amniótico/metabolismo , Micropartículas Derivadas de Células/metabolismo , Feminino , Sangue Fetal/química , Humanos , GravidezRESUMO
OBJECTIVES: In the working hypothesis we assumed that the procoagulant activity of microparticles (MPs) is associated with the concentration of tissue factor (TF) and its inhibitor (TFPI), and that these three components together affect fetal hemostasis. The aim of the study was to check whether MPs are present in the cord blood, to compare their concentration with that in the maternal blood, as well as to measure the concentrations of TF antigen and TFPI antigen in the cord blood and maternal blood. STUDY DESIGN: The study group consisted of 28 healthy parturient women who gave normal delivery, and their 28 babies. Blood from the umbilical vein was collected immediately after delivery, still prior to omphalotomy, whereas mother's blood was obtained from the antecubital vein. The concentration of MPs as well as TF antigen and TFPI antigen were measured using ELISA method. RESULTS: The level of MPs in cord blood plasma was found to be 6.25 times higher than in the mother's blood plasma (median: 26.76 nM PS; range: 22.90-34.41 nM PS vs. median: 4.26 nM PS; range: 2.68-5.37 nM PS respectively, p=0.0022), whereas the level of TF antigen was 1.94 times higher in the fetus than in the mother (median: 238.03 pg/ml; range: 192.25-283.10 pg/ml vs. median: 122.4 pg/ml, range: 52.71-176.74 pg/ml, respectively, p=0.0012). On the other hand, the level of TFPI antigen was lower in cord blood plasma than in maternal blood plasma, accounting for 33.95% of the value noted in the mother (median: 30.04 ng/ml, range: 24.84-35.12 ng/ml vs. median: 88.48 ng/ml; range: 78.64-107.20 ng/ml, respectively, p<0.0001). There was no correlation between MP concentration and the levels of TF as well as TFPI in fetal blood and maternal blood. CONCLUSIONS: Microparticles (MPs) are constituent components of cord blood plasma; their concentration is significantly higher than that in mother's blood plasma. In the fetus, MPs may play a role of a powerful procoagulant, thus facilitating thrombin generation (TF-dependent thrombin generation, which may take place on their surface); this hypothesis is based on literature data and our own evidence.
Assuntos
Micropartículas Derivadas de Células/metabolismo , Sangue Fetal/metabolismo , Lipoproteínas/sangue , Tromboplastina/metabolismo , Adulto , Feminino , Humanos , Projetos Piloto , Gravidez , Adulto JovemRESUMO
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.
Assuntos
Líquido Amniótico/fisiologia , Embolia Amniótica/etiologia , Ruptura Prematura de Membranas Fetais/etiologia , Pré-Eclâmpsia/sangue , Líquido Amniótico/química , Coagulação Sanguínea , Feminino , Fibrinolisina/metabolismo , Fibrinólise/fisiologia , Humanos , Fosfatidilserinas/fisiologia , Gravidez , Trombina/metabolismo , Tromboplastina/fisiologiaRESUMO
Activated protein C (APC) is an important anticoagulant which plays a role in pathophysiology of pregnancy, e.g. in maintenance of the uteroplacental circulation and development of the fetus as well as in pathogenesis of preeclampsia. The study objective was to compare the levels of the respective components of the protein C system (protein C, PC; protein S, PS; thrombomodulin, TM) as well as thrombin activatable fibrinolysis inhibitor - TAFI in mother's blood, cord blood and amniotic fluid. The study group consisted of 136 healthy parturients at term, divided into subgroups of 30-35. The immunoenzymatic method (ELISA) was used to measure the antigens of the components studied. The concentrations of PC and PS antigens were the highest in the mother's blood plasma (135.11+/-1.05% and 92.0+/-13.24%, respectively), lower in cord blood plasma (57.60+/-10.32% and 33.19+/-4.96%, respectively) and the lowest in amniotic fluid (6.75+/-3.50% and 2.40+/-1.64%, respectively); the differences between the levels of that of mother, fetus and amniotic fluid were statistically significant (p< or =0.0001). The TM and TAFI antigen concentrations were the highest in cord blood plasma (11.35+/-3.71 ng/ml and 91.50 (median; range: 71.76-160.77) ng/ml, respectively) and lower in maternal plasma (4.51+/-0.71 ng/ml and 55.46 - median; range: 39.77-68.54 ng/ml, respectively); the differences between the levels of that of cord blood plasma and maternal plasma were statistically significant (p< or =0.0001). Of the three protein C system components, PC and PS occur in relatively high concentrations in maternal blood, being lower in fetal blood and the lowest in amniotic fluid. On the other hand, as an exception, the concentrations of TM and TAFI are the highest in fetus blood.
Assuntos
Líquido Amniótico/metabolismo , Sangue Fetal/metabolismo , Gravidez/sangue , Proteína C/metabolismo , Adulto , Ensaio de Imunoadsorção Enzimática , Feminino , Humanos , Trabalho de Parto/sangue , Proteína S/metabolismo , Adulto JovemRESUMO
In intrauterine life, hemostasis is maintained by the same components as in extrauterine life (blood platelets, coagulation and fibrinolysis systems, involvement of the vascular wall); in the fetus, however, these components show significant differences of a quantitative/qualitative nature. In the present study, we surveyed the literature on the coagulation system in the fetus. We focused on the velocity of development of the coagulation system, being reflected in the increased concentration of all procoagulants and anticoagulants (a rise from approximately 20% in the middle of pregnancy to about 60% or more in the period of labor; exceptions: factors V, VIII and XIII which in the labor period reach the adult level) and screening test results (prothrombin time, aPTT - activated prothrombin time, and thrombin time). Reference values were given for the 19-38 weeks of pregnancy and the labor term. Biochemical features of fetal fibrinogen and PIVKA factors were also discussed. The role of activated protein C (APC) in the maintenance of balance between procoagulants and anticoagulants was postulated as well as the role of APC in the formation of thrombin activatable fibrinolysis inhibitor (TAFI).
Assuntos
Anticoagulantes/sangue , Fatores de Coagulação Sanguínea/metabolismo , Sangue Fetal/metabolismo , Adulto , Feminino , Idade Gestacional , Hemostasia/fisiologia , Humanos , Gravidez , Proteína C/metabolismo , Trombina/metabolismoRESUMO
AIM: P-selectin is a member of selectin family (E, L- and P-selectins) which plays a crucial role in reproduction and hemostasis as well as in pathogenesis of preeclampsia. There are no regular studies on P-selectin in placenta and it is not clear whether it is present in gestational myometrium. In the present study, we have asked whether P-selectin is present in placenta and myometrium and in what concentration. MATERIAL AND METHODS: The study group consisted of 33 healthy pregnant women at term and/or at the beginning of labor who delivered by cesarean section because of fetal distress or elective reasons. Strips of placenta and myometrium as well as venous blood were obtained during the operation. P-selectin was measured in tissue extracts and plasma with the use of immunoenzymatic assays (ELISA). RESULTS: The median of the level of P-selectin in placenta was 31.65 ng/mg P (total protein), quartiles (Q1-Q3): 24.54-43.35 ng/mg P, and in myometrium 25.54 ng/mg P, quartiles (Q1-Q3): 21.83-35.65 ng/mg P, whereas the median and quartiles (Q1-Q3) of soluble P-selectin in the mother's plasma was 1.14: 0.76-1.63 ng/mg P. The plasma/tissue ratio for placenta was 1:30, and for myometrium -1:25. CONCLUSIONS: P-selectin is present in placenta and gestational myometrium; its concentration is relatively high - respectively 30- and 25-times higher than in plasma. On the basis of our studies, we hypothesize about the role of placental and myometrial P-selectin in hemostasis of placental bed after labor.
Assuntos
Miométrio/química , Selectina-P/análise , Placenta/química , Adulto , Cesárea , Estudos de Coortes , Feminino , Hemostasia/fisiologia , Humanos , Selectina-P/fisiologia , GravidezRESUMO
Thrombin activatable fibrinolysis inhibitor (TAFI) is a plasma zymogene (procarboxypeptidase B) which can decrease fibrinolysis and thus act as a haemostatic factor. TAFI is now extensively studied in many complications as well as in physiological and complicated pregnancy. The question we posed in the present study was whether TAFI antigen is present in cord blood plasma. The study group consisted of 38 parturient women, 26 primiparous and 12 multiparous with normal course of pregnancy and delivery. The cord blood was sampled from the cord vein, and the mother's blood from the antecubital vein. 3.2% sodium citrate was used as an anticoagulant. TAFIa/ai antigen was measured by ELISA method. TAFIa/ai antigen was identified in all samples of cord blood plasma. Its level was 91.50 ng/ml (range: 71.76 - 160.77 ng/ml) vs. 55.46 ng/ml (range: 39.77 - 68.54 ng/ml ) in the mother's blood, which means that the level of TAFIa/ai antigen was significantly higher in fetal blood than in maternal blood (p<0.00001). TAFIa/ai antigen is an integral component of cord blood plasma. The concentration of TAFIa/ai antigen is about two times higher in fetal blood than in maternal blood.
Assuntos
Carboxipeptidase B2/sangue , Sangue Fetal/enzimologia , Adulto , Feminino , Sangue Fetal/metabolismo , Humanos , Parto/sangue , GravidezRESUMO
Thrombin activatable fibrinolysis inhibitor (TAFI) has been studied in normal and complicated pregnancies by a number of investigators, but there is no information on TAFI in amniotic fluid. In our study we asked two questions: (i) whether TAFI is present in amniotic fluid and in what concentration, (ii) whether its concentration is comparable to that in the blood. The study group consisted of 68 parturient women in the first stage of labour. 20 age-matched non-pregnant women constituted the control group. TAFI antigen was measured by immunoenzymatic method (ELISA) and TAFI activity with Actichrome Plasma TAFI Activity Kit by American Diagnostica. The concentration of TAFI antigen in amniotic fluid was 53.25 ng/ml (median) (range: 44.58-76.20 ng/ml) and in mothers' plasma it was 55.46 ng/ml (median) (range: 39.77-68.54 ng/ml); the difference was not statistically significant (p>0.3388). TAFI activity in amniotic fluid was relatively low (median: 3.00 microg/ml, range 0.50-5.45 microg/ml), while the activity in the mothers' plasma was more than three times higher (median 10.50 microg/ml; range: 7.60-13.50 microg/ml) (p<0.0004). TAFI antigen and TAFI activity in plasma of non-pregnant women were as high as in plasma of delivering women. We have concluded that TAFI is a physiological constituent of amniotic fluid. It is possible that TAFI is partially accountable for the antifibrinolytic potential of amniotic fluid.
Assuntos
Líquido Amniótico/química , Carboxipeptidase B2/análise , Adolescente , Adulto , Carboxipeptidase B2/sangue , Estudos de Casos e Controles , Feminino , Humanos , Trabalho de Parto/sangue , Parto/sangue , GravidezRESUMO
UNLABELLED: THE BACKGROUND: It is believed that annexin V, an anticoagulant protein abundant in trophoblast, prevents circulating blood in the intervillous space from hypercoagulability and fibrin deposition. Distribution and the role of annexin V localized in other gestational tissues like myometrium and fetal membranes, as well as in amniotic fluid is unknown. The aim of this study was to determine the concentration of annexin V in the tissues under consideration. STUDY DESIGN: The study group consisted of 40 healthy women at the 1st stage of labour, 16 of whom delivered by cesarean section. The strips of myometrium, placenta and fetal membranes, as well as the samples of amniotic fluid and the venous blood, were collected during surgery. Homogenates were prepared from the tissues. Annexin V was measured by immunoenzymatic method (ELISA). RESULTS: Concentration of annexin V in the placenta was 122.65 +/- 33,14 ng/mg protein, in fetal membranes 136.31 +/- 49.30 ng/mg protein and in myometrium 65.40 +/- 30.72 ng/mg protein. There was a statistical difference between the concentrations in placenta and fetal membranes vs. myometrium (p<0.05). In amniotic fluid annexin V was found to be in low concentration (4.46 +/- 2.59 ng/ml, i.e., 1.60 +/- 1.21 ng/mg protein) while in blood plasma it was extremely low, over 6000 times lower than in placenta. CONCLUSION: Annexin V is present not only in placenta, but also in fetal membranes and myometrium. Its concentration in fetal membranes is similar to that in placenta, while in myometrium it is 50% lower. Annexin V found in newly discovered sites probably plays a similar role like placental annexin V.
Assuntos
Líquido Amniótico/química , Anexina A5/análise , Membranas Extraembrionárias/química , Miométrio/química , Placenta/química , Adulto , Ensaio de Imunoadsorção Enzimática , Feminino , Humanos , Paridade , Gravidez/metabolismo , Valores de ReferênciaRESUMO
OBJECTIVES: The main components of protein C anticoagulant system are protein C (PC), protein S (PS) and thrombomodulin (TM); the system plays a protective role in pregnancy, mainly because it prevents the utero-placental circulation from local thrombosis. It is unknown whether the protein C anticoagulant pathway exists in amniotic fluid. The aim of the present study is to find out whether these three components are present in amniotic fluid. STUDY DESIGN: The study group consisted of 50 parturients with an uneventful pregnancy and birth and 25 non-pregnant controls. Amniotic fluid and blood were sampled at the end of the 1st stage of labor. PC, PS and TM were measured by immunoenzymatic method. RESULTS: All the samples of amniotic fluid contained measurable amounts of antigens of PC, PS and TM, although their concentrations were significantly lower than in the mother's blood: (i) The concentration of PC in amniotic fluid was 6.24+/-3.50% and PS 2.40+/-1.64%, while in the mothers' plasma it was 138.26+/-12.38% and 93.15+/-13.24%, respectively (P<0.0001). (ii) TM concentration in amniotic fluid constituted 63.92% of the concentration in the mother's blood (2.71+/-1.21 ng/mL vs. 4.24+/-0.88 ng/mL, P<0.001). CONCLUSION: Protein C, protein S and thrombomodulin are physiological constituents of the amniotic fluid. As their concentrations are low, it is reasonable to assume that they cannot counterbalance the procoagulant activity of amniotic fluid.
Assuntos
Líquido Amniótico/química , Proteína C/análise , Proteína S/análise , Trombomodulina/análise , Adulto , Coagulação Sanguínea/fisiologia , Estudos de Casos e Controles , Feminino , Humanos , Primeira Fase do Trabalho de Parto/sangue , Primeira Fase do Trabalho de Parto/metabolismo , Gravidez , Trombomodulina/sangueRESUMO
OBJECTIVES: Hypercoagulability is a well known feature of pregnancy, while hypocoagulability is attributed to newborns. The level of thrombin markers in the blood reflects the relations in coagulation system. We have measured two markers of thrombin generation, e.i prothrombin fragments F 1+2 and thrombin-antithrombin III complexes (TAT), in the cord blood and the mother's blood, as well as in amniotic fluid. MATERIAL AND METHODS: The study group consisted of 33 parturient women, 24.2 +/- 3.6 years old, 20 primiparas and 13 multiparas with normal course of pregnancy. The level of F 1+2 and the level of TAT were estimated by ELISA method. RESULTS: The highest level of F 1+2 and TAT was in amniotic fluid, e.i. 29.99 (9.15 - 50.75) nmol/l vs. 519.62 +/- 270.51 microg/l. In the blood cord the level of F 1+2 was 7.15 (5.05 - 22.05) nmol/l, and the level of TAT was 151.57 +/- 134.17 microg/l. In the mother's blood plasma the levels of F 1+2 and TAT were significantly lower than in cord blood (5.15, range 3.50 - 6.05 nmol/l vs. 36.30 +/- 18.65 microg/l respectively, p < 0.001). CONCLUSION: Increased generation of thrombin in foetal blood which is reflected in increased levels of F 1+2 and TAT, is one of the features of "foetal phenomenon" concerning foetal coagulation system. High concentration of F 1+2 and TAT in amniotic fluid can be consider to be a result of increased thrombin generation or the lowered metabolism of F 1+2 and TAT.
Assuntos
Líquido Amniótico/metabolismo , Antitrombina III/análise , Sangue Fetal/metabolismo , Fragmentos de Peptídeos/análise , Peptídeo Hidrolases/análise , Protrombina/análise , Adulto , Biomarcadores/análise , Estudos de Casos e Controles , Ensaio de Imunoadsorção Enzimática , Feminino , Humanos , Gravidez/sangue , Estatísticas não ParamétricasRESUMO
BACKGROUND: Urokinase plasminogen activator (uPA) and urokinase plasminogen activator receptor (uPAR) are central molecules for uPA/uPAR/plasmin-dependent proteolysis, which is thought to play a significant role in the development of pregnancy, as well as its many complications. OBJECTIVE: To measure the levels of uPA and uPAR in the placenta and myometrium, as well as in the foetal membranes and amniotic fluid. STUDY DESIGN: The study group consisted of 35 women with normal course of pregnancy, but with complications arising during delivery, which led to Caesarean section. Samples of placenta, myometrium, foetal membranes, amniotic fluid and blood were obtained at the time of operation. Tissue extracts were prepared. Measurements were made by the ELISA method. RESULTS: uPA and uPAR concentration in gestational tissues, including amniotic fluid, is 100-200 times higher than in plasma. Among tissues, the highest uPA level was found in placenta ( 1.32 +/- 0.48 ng/mg of protein), and the highest uPAR level in foetal membranes (3.33 +/- 1.20 ng/mg of protein). CONCLUSIONS: uPA and uPAR are present in all gestational tissues, in some in relatively high concentrations. Our results support the modern clinical hypothesis that fibrinolytic system can participate in mechanisms of such obstetric complications as pre-term pre-mature rupture of foetal membranes and placental abruption.
Assuntos
Placenta/metabolismo , Gravidez/metabolismo , Receptores de Superfície Celular/metabolismo , Ativador de Plasminogênio Tipo Uroquinase/metabolismo , Adulto , Líquido Amniótico/metabolismo , Estudos de Casos e Controles , Ensaio de Imunoadsorção Enzimática , Membranas Extraembrionárias/metabolismo , Feminino , Humanos , Miométrio/metabolismo , Paridade , Receptores de Ativador de Plasminogênio Tipo UroquinaseRESUMO
OBJECTIVE: To develop the hypothesis on biochemical mechanism of the placenta accreta and to review the epidemiological information on that complication. STUDY DESIGN: Data collected in 1995-2002 in the Medline System were the main source of analyzed literature. RESULTS: Placenta accreta occurs in approximately 1 of 2500 deliveries, however among women with placenta praevia, the incidence is nearly 10%. Independent risk factors for placenta accreta are previous cesarean delivery and maternal age > or =35 years. Postpartum hemorrhage is the main cause of maternal mortality. Hysterectomy is often performed to save the life of the mother. Ligation of internal pelvic arteries is considered to be ineffective procedure in about 50%. An another option in management of hemorrhage is embolisation of pelvic arteries. Recombinant factor VIIa is recommended is a new agent in pharmacological therapy. Our hypothesis is as follows: The complex of uPA/uPAR (urokinase plasminogen activator/receptor of urokinase plasminogen activator complex) plays crucial role in the generation of plasmin-dependent proteolysis, which takes place in the surface of trophoblast. Penetration of the villi into the tissues is controlled by plasminogen activator inhibitors--plasminogen activator inhibitor 1 (PAI-1) and plasminogen activator inhibitor 2 (PAI-2), mainly by PAI-2. PAI-2 inactivates uPA/uPAR complexes forming triplicate complexes. If the PAI-2 concentration in placenta and myometrium is low, the invasion of placenta villi is excessive. CONCLUSION: Disturbance of balance between plasminogen activator and their inhibitors (PAI-1 and PAI-2) in placenta and myometrium can lead to the formation of placenta accreta.
Assuntos
Placenta Acreta/epidemiologia , Placenta Acreta/metabolismo , Ativadores de Plasminogênio/metabolismo , Inativadores de Plasminogênio/metabolismo , Ativador de Plasminogênio Tipo Uroquinase/metabolismo , Adulto , Cesárea/efeitos adversos , Feminino , Humanos , Histerectomia , Incidência , Placenta Prévia/epidemiologia , Placenta Prévia/metabolismo , Inibidor 1 de Ativador de Plasminogênio/metabolismo , Inibidor 2 de Ativador de Plasminogênio/metabolismo , Hemorragia Pós-Parto/etiologia , Gravidez , Receptores de Superfície Celular/metabolismo , Receptores de Ativador de Plasminogênio Tipo Uroquinase , Fatores de RiscoRESUMO
UNLABELLED: The concentration of TAFI in cord blood plasma has not been studied yet. We have measured its activity in plasma both in cord blood and mother's blood during labour. The study group consisted of 26 parturient women, 18 primiparas and 9 multiparas with normal course of pregnancy and delivery. Activity of TAFI was evaluated by chromogenic method (Actichrome Plasma TAFI Activity Kit). The level of TAFI in cord blood plasma was 4.20, range 3.80-6.40 micrograms/ml and in mother's blood 10.50, range 7.60-13.50 micrograms/ml, thus it was significantly lower (p < 0.0001). CONCLUSION: TAFI is present in the cord blood plasma but its concentration is about 50% of that in the mother's blood.
Assuntos
Carboxipeptidase B2/sangue , Sangue Fetal/metabolismo , Trabalho de Parto/sangue , Período Pós-Parto/sangue , Adulto , Estudos de Casos e Controles , Feminino , Humanos , Recém-Nascido , Gravidez , Valores de ReferênciaRESUMO
The study gives a survey of literature on obstetric aspects of hereditary thrombophilias e.i. factor V Leiden, prothrombin gene 20210A mutation, antithrombin III deficiency, protein C/protein S deficiency, and hyperhomocysteinemia. All types of thrombophilia cause similar pathomorphological changes in placenta and decidua (high number of infarcts and microclots, decidual vasculopathia) as well as insufficient invasion of cytotrophoblast in spiral arteries. The study also discusses prophylactic rules: application of low molecular weight heparin and non-fractionated heparin in prophylaxis and in hyperhomocysteinemia application of folic acid.
Assuntos
Mutação , Complicações do Trabalho de Parto/etiologia , Complicações do Trabalho de Parto/prevenção & controle , Trombofilia/complicações , Trombofilia/tratamento farmacológico , Aborto Habitual/etiologia , Aborto Habitual/prevenção & controle , Anticoagulantes/uso terapêutico , Antitrombina III/genética , Deficiência de Antitrombina III/complicações , Deficiência de Antitrombina III/tratamento farmacológico , Coagulação Sanguínea/efeitos dos fármacos , Fator V/genética , Feminino , Fibrinolíticos/uso terapêutico , Humanos , Hiper-Homocisteinemia/complicações , Hiper-Homocisteinemia/tratamento farmacológico , Complicações do Trabalho de Parto/epidemiologia , Gravidez , Proteína C/genética , Deficiência de Proteína C/complicações , Deficiência de Proteína C/tratamento farmacológico , Proteína S/genética , Deficiência de Proteína S/complicações , Deficiência de Proteína S/tratamento farmacológico , Protrombina/genética , Trombofilia/epidemiologia , Trombofilia/genéticaRESUMO
The paper is a survey of literature on the two hypotheses about preeclampsia: a) one according to which the endothelium injury is a key complication; b) another one according to which the injury is a side effect of inflammation and adhesive reaction. Those reactions consist in the activation of the endothelium and activation of blood platelets, as well as activation of neutrophils and monocytes/macrophages. That complex activation is induced by cytokines and integrins from the placenta, deported cytotrophoblast and procoagulant debris of the trophoblast. The two hypotheses are complementary rather than competitive.
Assuntos
Endotélio Vascular/metabolismo , Pré-Eclâmpsia/metabolismo , Plaquetas/metabolismo , Endotélio Vascular/imunologia , Feminino , Humanos , Macrófagos/metabolismo , Monócitos/metabolismo , Ativação de Neutrófilo , Placenta/metabolismo , Ativação Plaquetária , Pré-Eclâmpsia/imunologia , GravidezRESUMO
BACKGROUND: Placental abruption is mainly due to the rupture of the uterine spiral arteries, but adjacent tissues are also damaged and substances derived from disintegrated placenta and myometrium probably cause coagulation disturbances, such as hypofibrinogenemia and disseminated intravascular coagulation (DIC). AIM: To measure whether placenta and myometrium are significant sources of tissue factor (TF) and tissue factor pathway inhibitor (TFPI), the components of key role in the initiation of coagulation. MATERIALS AND METHODS: Strips of placenta and myometrium were obtained from 48 women delivered by cesarean section at term. TF and TFPI concentrations were measured by immunoenzymatic method (ELISA) in tissue homogenates. MAIN RESULTS: Concentration of TF in placenta and myometrium was 31 (25-37) and 7.4 (4.9-11.4) ng/mg of total protein, respectively. In the plasma of the same women, it was 0.004ng/mg of total protein. TFPI concentration was 13 (10-17) ng/mg of total protein in placenta, 4.5 (3.1-7.3) ng/mg in myometrium, and 0.70 (0.50-0.80) ng/mg in blood plasma protein. CONCLUSION: The levels of TF in placenta and myometrium, over TF in blood plasma may be clinically significant in obstetrics, for instance, in the etiology of DIC in placental abruption. The concentration of TFPI-natural inhibitor of TF-seems to be too low to prevent initiation of coagulation.