The Contact Activation System (CAS) in cord blood: Measurement of CAS components and comparison with mother's blood. A pilot study.

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.

Activation contact system (ACS) and tissue factor (TF) in human amniotic fluid: measurements of ACS components and TF, and some implications on the pathophysiology of amniotic fluid embolism.

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.

New observations on procoagulant properties of amniotic fluid: microparticles (MPs) and tissue factor-bearing MPs (MPs-TF), comparison with maternal blood plasma.

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.

Microparticles (MPs), tissue factor (TF) and tissue factor inhibitor (TFPI) in cord blood plasma. A preliminary study and literature survey of procoagulant properties of MPs.

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.

Coagulation and fibrinolysis in amniotic fluid: physiology and observations on amniotic fluid embolism, preterm fetal membrane rupture, and pre-eclampsia.

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.

A comparative study of the protein C system in mother's blood, cord blood and amniotic fluid.

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.

Procoagulants and anticoagulants in fetal blood. A literature survey.

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).

P-selectin in placenta and gestational myometrium: its measurements and hypothetical role in hemostasis of placental bed after labor.

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.

Thrombin activatable fibrinolysis inhibitor (TAFI) in cord blood.

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.

Thrombin activatable fibrinolysis inhibitor (TAFI) in human amniotic fluid. A preliminary study.

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.

[Concentration of annexin V in gestational tissues: placenta, fetal membranes, myometrium and amniotic fluid]. / Stezenie aneksyny V w tkankach polozniczych: lozysko, blony plodowe i myometrium oraz plyn owodniowy.

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.

Protein C, protein S, and thrombomodulin in amniotic fluid. A preliminary study.

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.

[Novel treatment for severe sepsis: recombinant human protein C (RHAPC)]. / Rekombinowane bialko C--nowy lek do leczenia ciezkich infekcji, perspektywy stosowania w poloznictwie.

STUDY DESIGN: Review of literature on novel therapy for severe sepsis within recombinant human protein C (rhAPC). DATA SELECTION: MEDLINE and Polska Bibliografia Lekarska (2000-2003) were the main sources of the reviewed articles. DATA SYNTHESIS: Despite advances in critical care the rate of death from severe sepsis ranges from 30 to 50 percent (data related to patients with this complication treated in the intensive care units in the United States). In Poland about one third (27.3%) of all maternal deaths in 1991-2000 were from severe sepsis. Since the introduction of antibiotics, the first significant progress in effective therapy for severe sepsis was achieved due to the novel therapy within rhAPC. In 2001 Bernard et al. reported results of multi-center, placebo-controlled, randomized trial, in which the administration of rhAPC at 24 microgram/kg/h/96 hrs increased the survival in patients with severe sepsis by 6.1% (mortality rate was 24.7% for rhAPC group, while 30.8% for placebo group). There was an insignificant tendency for more bleeding in rhAPC patients (3.5% vs. 2.0% with placebo). In 2003 Dhainaut et al. described the pharmacological effects of rhAPC on severe sepsis. Fifteen biomarkers of inflammation or thrombosis/fibrinolysis were monitored. It was established that rhAPC decreases host response to infection resulting in lowering the levels of all inflammatory cytokines (TNFalfa, IL-1, IL-6 and IL-8), as well as lowering procoagulant markers, mainly D-dimers. CONCLUSION: Sufficient data are available to approve rhAPC for treatment of patients with severe sepsis. Both anticoagulant and antiinflammatory properties of rhAPC, as well as profibrinolytic activity, are the rationale for the use of rhAPC.

[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]. / Markery trombiny u kobiety rodzacej: pomiary stezenia fragmentów protrombiny 1+2 (F 1+2) i kompleksów trombina-antytrombina III (TAT) we krwi matki i krwi pepowinowej oraz plynie owodniowym.

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.

[Problems of recurrent loss of pregnancy: are procoagulant microparticles a risk factor for pregnancy outcome?]. / Problemy powtarzajacej sie utraty ciazy: czy krazacy prokoagulant komórkowy stanowi ryzyko utraty ciazy?

BACKGROUND: Circulating procoagulant microparticles (PM) are a novel risk factor for pregnancy outcome. They derive from cytosol and membranes of the cells undergoing apoptosis or pathological activation. Tissue factor and phospholipids are the active components of PM responsible for "placental thrombosis" and pregnancy loss. STUDY DESIGN: The paper is a survey of the literature on the pathological role of PM in complicated pregnancy. RESULTS AND CONCLUSIONS: The published studies suggest that PM play a role of a pathogenic factor in women with repeated pregnancy loss. Prophylaxis within low-molecular heparin is a promising clinical procedure.

Urokinase plasminogen activator (uPA) and its receptor (uPAR) in gestational tissues; Measurements and clinical implications.

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.

[Placenta accreta: epidemiology, molecular mechanism (hypothesis) and some clinical remarks]. / Lozysko wrosniete: informacje epidemiologiczne, molekularny mechanizm powiklania i uwagi o postipowaniu klinicznym.

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.

[Concentration of thrombin activatable fibrinolysis inhibitor (TAFI) in cord blood and maternal blood during labor]. / Trombinowy inhibitor fibrynolizy (TAFI) we krwi pepowinowej plodu i krwi matki.

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.