The relation between the concentration of placental specific proteins in retroplacental and peripheral blood.

Concentrations of four placental proteins: human placental lactogen (hPL), placental protein 5 (PP5), pregnancy specific beta 1 glycoprotein (SP1) and human chorionic gonadotrophin (hCG), and a normal serum component, alpha 2 macroglobulin, were measured in the peripheral circulation and in blood obtained from the retroplacental space in 20 women at term delivery. Levels of hPL and PP5 were higher in the retroplacental blood than in the peripheral circulation in all patients. By contrast, levels of SP1 and hCG were consistently lower in retroplacental blood than in the peripheral circulation. Similarly, levels of alpha 2 macroglobulin were lower in the retroplacental blood. It is suggested that this 'reverse' gradient is a technical arterfact. These findings are discussed in relation to synthesis of placental proteins in a site distal to the retroplacental space, and the introduction of a technical artefact in the collection of samples.     

血清可溶性血管内皮生长因子受体与子痫前期发病的关系

目的探讨血清中可溶性血管内皮生长因子受体1(sFlt-1)的变化及其与子痫前期发病的关系。方法(1)应用半定量RT-PCR技术检测10例重度子痫前期患者(子痫前期组)及10例足月正常妊娠妇女(正常妊娠组)的胎盘组织中sFlt-1mRNA表达水平。(2)应用酶联免疫吸附试验(ELISA)法测定35例重度子痫前期患者(子痫前期1组)及35例正常足月妊娠妇女(正常妊娠1组)外周血中sFlt-1水平。(3)ELISA测定20例重度子痫前期患者(子痫前期2组)及20例正常足月妊娠妇女(正常妊娠2组)胎盘附着处子宫静脉血中sFlt-1水平。(4)ELISA测定10例早孕(早孕组)及10例中孕(中孕组)妇女外周血中sFlt-1水平。结果(1)子痫前期组胎盘组织中sFlt-1mRNA表达水平为0.95±0.04,明显高于正常妊娠组的0.64±0.15,两组比较,差异有统计学意义(P<0.01)。(2)子痫前期1组孕妇外周血清中sFlt-1水平为(5640±3191)ng/L,明显高于正常妊娠1组的(2194±635)ng/L,两组比较,差异有统计学意义(P<0.01)。(3)子痫前期2组孕妇子宫静脉血清中sFlt-1水平为(7673±2296)ng/L,明显高于正常妊娠2组的(3057±785)ng/L,两组比较,差异有统计学意义(P<0.01)。(4)早、中孕组孕妇外周血清中sFlt-1水平分别为(32±20)ng/L及(994±302)ng/L。结论(1)子痫前期患者外周血中sFlt-1水平明显增高;(2)血清中sFlt-1水平随孕周增加而升高,并可能与子痫前期的发病有关。     

Protein S and protein C levels in Chinese women during pregnancy, delivery and the puerperium

Summary. The plasma levels of protein S and protein C related antigens were determined in a group of normal pregnant Chinese women and a group of normal non-pregnant controls, using the sandwich technique of enzyme immunoassay with commercial kits. Compared with non-pregnant controls, plasma protein S levels were significantly lower during pregnancy, labour, parturition and the early puerperium. There was no significant difference in protein S levels between pregnancy, labour and puerperium. On the other hand, maternal plasma protein C levels during pregnancy and before delivery were similar to those in controls, but a significant increase was found during the third stage of labour. This increase did not persist into the early puerperium. The observed increase in protein C level immediately after delivery in our study may represent a physiological response to counter the tendency towards venous thrombosis in the parturient women, and may help to explain the almost negligible occurrence of thromboembolism in Chinese obstetric patients.     

Protein S and protein C levels in Chinese women during pregnancy, delivery and the puerperium

The plasma levels of protein S and protein C related antigens were determined in a group of normal pregnant Chinese women and a group of normal non-pregnant controls, using the sandwich technique of enzyme immunoassay with commercial kits. Compared with non-pregnant controls, plasma protein S levels were significantly lower during pregnancy, labour, parturition and the early puerperium. There was no significant difference in protein S levels between pregnancy, labour and puerperium. On the other hand, maternal plasma protein C levels during pregnancy and before delivery were similar to those in controls, but a significant increase was found during the third stage of labour. This increase did not persist into the early puerperium. The observed increase in protein C level immediately after delivery in our study may represent a physiological response to counter the tendency towards venous thrombosis in the parturient women, and may help to explain the almost negligible occurrence of thromboembolism in Chinese obstetric patients.     

Studies on pregnancy-associated plasma protein A in the third trimester of pregnancy.

The plasma concentration of pregnancy-associated plasma protein A (PAPP-A) was measured in 34 women during the last 10 weeks of pregnancy. From 30 to 36 weeks the concentration of this protein increased steadily. Thereafter the concentration of PAPP-A rose more steeply, the highest amounts being found in early labour. The concentration of PAPP-A in peripheral venous blood and in the uterine vein was much the same. It was less in the retroplacental blood and a great deal less in the peritoneal fluid. The day-to-day variation was small; the coefficient of variation at 38 weeks was only 7.3 per cent. After delivery, the concentration of PAPP-A fell more slowly than other placental proteins and steroids, the average half-life being 51 hours. Although there is no doubt that PAPP-A is a product of the syncytiotrophoblast, our findings suggest that it is not simply secreted by the chorionic villi directly into the intervillous space but makes its way into the maternal circulation by a more circuitous route.     

Coagulation inhibitors in preeclamptic pregnant women

Objective Our objective was to detect clinical evaluation of coagulation inhibitors in preeclamptic and normotensive pregnant women and to determine their important role in pathogenesis of preeclampsia.Methods A total of 20 mild, 20 severe preeclamptic and 45 normotensive pregnant women were included in this study. The plasma value of antithrombin III (AT-III) activity, proteins C and S activity, PT, PTT, fibrinogen and platelet counts were determined.Results The values AT-III were lower in women with severe preeclampsia than in controls (p<0.05). In all groups, there was no significantly difference in the concentration of protein C activity, protein S and fibrinogen (p>0.05). The plasma thrombocyte counts were significantly lower in severe preeclamptic women than in normotensive women (p<0.05). There was no significant difference in the prothrombin time value in all groups, but a significantly difference with regard to partial thromboplastin time between severe preeclamptic and the control group (p<0.0001). It was longer than the control.Conclusion The markers of hemostasis activation such as protein S, protein C activity together with fibrinogen levels are not useful tools but the reduction of AT-III and platelet counts would seem useful in different pathological situations in pregnancy to predict and monitor the severity of the condition.     

血液动力学指标预测胎儿缺氧及酸中毒的价值

目的：评价血液动力学指标预测胎儿缺氧及酸中毒的价值。方法：用彩色多普勒超声检测了４６例正常晚期妊娠（正常组）和３２例高危妊娠（高危组）妇女子宫动脉（ＵｔＡ）和胎儿脐动脉（ＵｍＡ）、大脑中动脉（ＭＣＡ）、肾动脉（ＲＡ）的血流速度波型，并且测定高危组脐动脉血气。结果：高危组ＵｔＡ、ＵｍＡ、ＲＡ的阻力指数（ＲＩ）、搏动指数（ＰＩ）及收缩期最大血流速度（Ｓ）与舒张末期血流速度（Ｄ）的比值（Ｓ／Ｄ值）均高于正常组，而ＭＣＡ的ＰＩ及Ｓ／Ｄ值均明显低于正常组（Ｐ＜０．０５）。与ＵｍＡＰＯ２＞２．５ｋＰａ的高危妊娠病例比较，ＵｍＡＰＯ２≤２．５ｋＰａ者ＵｔＡ的Ｓ／Ｄ值、ＵｍＡ的ＰＩ、Ｓ／Ｄ值以及ＲＡ的ＲＩ、ＰＩ、Ｓ／Ｄ值均明显增高，ＭＣＡ的ＰＩ明显降低（Ｐ＜０．０５）。ＵｍＡ及ＲＡ的ＰＩ与ＵｍＡＰＯ２和ｐＨ值呈负相关，与ＰＣＯ２呈正相关；ＭＣＡ的ＰＩ与ＵｍＡ的ｐＨ、ＰＯ２呈正相关，与ＰＣＯ２呈负相关。结论：高危妊娠胎儿缺氧时ＭＣＡ血流阻力降低，而周围血管，特别是肾血管血流阻力明显升高；胎儿血液动力学变化与缺氧及酸碱平衡失调呈良好相关性，可预测胎儿缺氧及酸中毒的程度。     

Changes in the plasma activities of protein C and protein S during pregnancy

The objective of the study was to determine the changes in the plasma activities of protein C and protein S that occur during normal pregnancy In this prospective cross-sectional study, plasma activities of protein C and protein S were measured in 32 normal pregnant women in the first, second and third trimester and 6 weeks after delivery There was a significant fall in protein C and protein S activities during normal pregnancy compared with the post-puerperal period. The activities of protein C and protein S also gradually decreased throughout pregnancy (p < 0.01). Increasing plasma volume during normal pregnancy and its dilutional effect might play some role in the low activities of protein S observed. The normal falls in protein S and protein C activities make it difficult to diagnose protein S and C deficiency during pregnancy. Based on our findings, if a woman has a thromboembolic event during pregnancy, testing for a definitive diagnosis of protein C or protein S deficiency or functional failure should be delayed until at least 6 weeks postpartum.     

Relation of obstetric parameters to the concentrations of four pregnancy-associated plasma proteins at term in normal gestation.

The relations between normal obstetric parameters and the maternal levels of four pregnancy-associated plasma proteins (PAPP) were studied, with the use of plasma samples taken from 187 normal pregnant women within seven days before delivery. PAPP-A levels were correlated with placental and newborn weights. The levels of this pregnancy protein was higher in primigravid women and in groups with higher diastolic blood pressure than in other groups. Women with extremely high PAPP-A concentrations were likely to have extremely large placental weight was not necessarily associated with a high PAPP-A level. PAPP-C was not correlated with placental or newborn weight. The relationship between PAPP-C and maternal age, as well as maternal weight, was significant by one but not in the other three statistical analyses employed. The pregnancy zone protein was found to be correlated with parity. In primigravid women, this protein additionally showed an inverse correlation with the placental weight. Human chorionic somatomammotropin was significantly related to placental weight and inversely related to maternal weight. Its relationship with newborn weight was best seen in primigravid subjects. Other parameters (systolic blood pressure, one- and five-minute Apgar scores, weeks of gestation, days before delivery, newborn sex, and newborn bilirubin level) were not related to any of these pregnancy proteins.     

Intravascular Coagulation in Uterine Venous Blood of Toxemic Patients

Coagulation profile was investigated in blood drawn from the uterine vein of 12 patients undergoing cesarean section for moderate to moderately severe preeclampsia, and blood drawn peripherally at the same time. An identical study was made in a control group of 12 nontoxemic patients undergoing routine repeat cesarean section. In the control group, platelet counts and fibrinogen levels were always within normal limits, and there was no major difference between peripheral and uterine vein blood; fibrin degradation products (FDP) were uniformly absent. Compared to control patients, the preeclamptic patients showed in the peripheral blood drops in the platelet counts of 17 percent and in fibrinogen level of 5 percent, and in the uterine venous blood drops in the platelet counts of 43 percent and in fibrinogen level of 18 percent. FDP were present once in the peripheral blood and three times in the uterine venous blood. It appears that when blood passes through the toxemic placenta first there is consumption of thrombocytes, second fibrinogen to fibrin conversion, and then FDP formation.     

Blood coagulation and fibrinolytic studies in patients with toxemia of pregnancy

In this study, blood coagulation and fibrinolytic parameters were measured in maternal blood and fetal umbilical cord blood in 200 normal pregnant women and in 46 with severe toxemia of pregnancy (Toxemia), and the relationships between fetal growth and concentrations protein C (PC), antithrombin-III (AT-III) and alpha 2-plasmin inhibitor (alpha 2-PI) were studied. 1. Significant increases in fibrin degradation products (FDP) and in plasminogen (Plg), AT-III and PC were found in maternal blood of Toxemia. A significant increase in AT-III and a decrease in alpha 2-PI and PC were observed in cord blood from these patients. 2. The platelet count (Pl) tended to be low in patients with Toxemia complicated by fetal growth retardation (IUGR). 3. Pl and fibrinogen (Fib) tended to be high in Toxemia complicated by normal fetal growth. 4. PC increased from early pregnancy, and a further increase was observed in the puerperium. 5. The PC concentration correlated with the AT-III but not with the alpha 2-PI concentration in maternal blood. 6. PC in cord blood was lower than that in maternal blood, and was correlated with AT-III and alpha 2-PI. 7. In patients with Toxemia, PC was reduced in both maternal and cord blood, and this correlated with AT-III as well as alpha 2-PI in maternal blood. 8. PC was low in Toxemia complicated by hypertension and proteinuria. These results suggest the involvement of FDP, AT-III, PC and Plg in the pathogenesis of Toxemia, and that the Pl, Fib, FDP and alpha 2-PI concentrations are related to fetal growth. Therefore, the PC and AT-III concentrations appeared to be a useful index for the blood coagulation and fibrinolysis in pregnant women and appeared to be important factors in the degree of Toxemia and IUGR.     

妊娠期及产褥期静脉血栓12例临床分析

目的 探讨妊娠期和产褥期静脉血栓的发生率,病因诊断,预防和治疗。方法 回顾性分析１９８４年１月至１９９７年１２月间,我院住院诊治的１２例妊娠期及产褥期深静脉血栓栓塞患者的临床资料,并对４例患者进行蛋白Ｃ、蛋白Ｓ、抗凝血酶Ⅲ活性和活化蛋白Ｃ抵抗（ＡＰＣ－Ｒ）的测定,同时进行凝血因子Ｖ（ＦＶ）１６９１位核苷酸基因变异（ＦＶ Ｌｅｉｄｅｎ变异）筛选。结果 ４例血栓发生在妊娠期,８例发生在产褥期;２例合并     

Factor V Leiden in pregnancies complicated by placental abruption

Objective Recent studies suggest an increased prevalence of obstetric complications in female carriers of hereditary or acquired thrombophilias. The aim of the study was to determine if carriership of the factor V (FV) Leiden mutation (activated protein C [APC] resistance) is higher in women who have had of placental abruption during pregnancy.
Design A retrospective case–control study.
Setting University Hospital MAS, Malmö, Sweden.
Methods A comparison of 102 women with placental abruption with 2371 prospectively collected controls. Carriership of FV Leiden was determined and the women were interviewed.
Main outcome measures Proportion of FV Leiden carriership, first degree heritage of thrombosis and previous placental abruption in cases and controls.
Results Carriage of FV Leiden was found in 15.7% of women who have had placental abruption as compared with 10.8% of controls (   P = 0.12, odds ratio [OR] = 1.5, 95% confidence interval [CI] = 0.9–2.7  ). Around 20% of women with placental abruption reported first degree heritage for venous thrombosis, as compared with 6.7% of controls (   P ≤ 0.001  ).
Conclusions FV Leiden carriership was not significantly different in women with placental abruption. However, there was an increased prevalence of first degree heritage for venous thrombosis in women with placental abruption, indicating a higher prevalence of thrombophilia among women with placental abruption.     

Preeclampsia: an imbalance in placental prostacyclin and thromboxane production

Preeclampsia is characterized by increased vasoconstriction frequently associated with increased platelet aggregation, reduced uteroplacental blood flow, and premature delivery. Because prostacyclin antagonizes the vasoconstrictor, platelet-aggregating, and uterine-activating actions of thromboxane, we considered the hypothesis that placental production of thromboxane was increased coincident with decreased production of prostacyclin in preeclampsia. Fresh human term placentas were obtained immediately after delivery from 11 normal and 10 preeclamptic pregnancies (blood pressure greater than or equal to 140/90 mm Hg, urinary protein greater than 0.3 gm/24 hr). Tissues (350 mg) were incubated sterilely in 6 ml of Dulbecco's Modified Eagle's Medium for 48 hours at 37 degrees C with 95% oxygen and 5% carbon dioxide in a metabolic shaker. Samples were collected at 8, 20, 32, and 48 hours and analyzed for thromboxane by radioimmunoassay of its stable metabolite, thromboxane B2, and for prostacyclin by radioimmunoassay of its stable metabolite, 6-keto prostaglandin F1 alpha. The production of thromboxane was significantly increased in preeclamptic versus normal placental tissue (22.9 +/- 4.7 versus 6.3 +/- 1.5 pg/mg/hr, mean +/- SE, p less than 0.01), whereas the production of prostacyclin was significantly decreased (3.0 +/- 0.3 versus 6.7 +/- 0.5 pg/mg/hr, p less than 0.001). In both normal and preeclamptic placentas, the production rates of thromboxane and prostacyclin were inhibited by indomethacin (5 mumol/L) and not affected (p greater than 0.50) by arachidonic acid (100 mumol/L). Therefore, during normal pregnancy, the placenta produces equivalent amounts of thromboxane and prostacyclin, so that their biologic actions on vascular tone, platelet aggregation, and uterine activity will be balanced. In preeclamptic pregnancy, however, the placenta produces seven times more thromboxane than prostacyclin.     

Childbirth and myoma treatment by uterine artery occlusion: do they share a common biology?

When the uterine arteries are bilaterally occluded, either by uterine artery embolization or by laparoscopic obstruction, women with myomas experience symptomatic relief. After the uterine arteries are occluded, most blood stops flowing in myometrial arteries and veins, and the uterus becomes ischemic. It is postulated that myomas are killed by the same process that kills trophoblasts: transient uterine ischemia. When the uterine arteries are bilaterally occluded, either by uterine artery embolization (UAE) or by laparoscopic obstruction, women with myomas experience symptomatic relief. After the uterine arteries are occluded, most blood stops flowing in myometrial arteries and veins, and the uterus becomes ischemic. Over time, stagnant blood in these arteries and veins clots. Then, tiny collateral arteries in the broad ligament (including communicating arteries from the ovarian arteries) open, causing clot within myometrium to lyse and the uterus to reperfuse. Myomas, however, do not survive this period of ischemia. This is unique organ response to clot formation and ischemia. What allows the uterus to survive a relatively long period of ischemia while myomas perish? Childbirth appears to be the predicate biology. Following placental separation, the uteroplacental arteries and the draining veins of the placenta are torn apart at their bases in the junctional zone of the myometrium and bleed directly into the uterine cavity. Left unchecked, every woman would bleed to death in less than 10 minutes after placental delivery. Most women do not bleed to death because vessels in the uterus clot after placental delivery. During pregnancy, clotting and lytic factors in blood increase many fold. Following delivery, uterine contractions continue, intermittently, periodically slowing the velocity of flowing blood through myometrium. The combination of slowed blood flow, elevated clotting proteins, and torn placental vessels (known as Virchow's triad) causes blood in myometrial arteries and veins to clot. Fibrinolytic enzymes later lyse clot in arteries and veins not associated with placenta perfusion, and the uterus is reperfused. Remnant placental tissue - primarily uteroplacental arteries and veins - does not survive this period of ischemia. Placental tissue dies and over weeks is sloughed into the uterine cavity. At the same time, residual endometrial tissue grows under the sloughing placental tissue thus re-establishing the endometrial lining. It is postulated that myomas are killed by the same process that kills trophoblasts - transient uterine ischemia.     

Effects of tibolone and continuous combined hormone replacement therapy on parameters in the clotting cascade: a multicenter, double-blind, randomized study

OBJECTIVE: To determine the effects of tibolone and continuous combined HRT (ccHRT) on parameters in the clotting cascade. DESIGN: Randomized, double-blind study. SETTING: Hemostasis unit of a university hospital clinic in Germany. PATIENT(S): Sixty healthy postmenopausal women. INTERVENTION(S): Twenty-nine subjects were treated with tibolone (2.5 mg/d) and 31 with oral ccHRT containing estradiol (2 mg/d) + estriol (1 mg/d) + norethindrone acetate (1 mg/d). MAIN OUTCOME MEASURE(S): Effects on parameters in the clotting cascade at baseline and after 12 and 24 weeks of treatment. RESULT(S): Tibolone increased fibrinolysis parameters without significantly altering coagulation parameters. Treatment with ccHRT resulted in a stimulating effect on parameters of both fibrinolysis and coagulation. Tibolone showed a stronger reduction of factor VII activity; less reduction of AT-III, protein C activity, and protein S activity; stronger increase of the activated partial thromboplastin time, plasminogen and plasminogen-antiplasminogen complexes; and less increase of D-Dimer than ccHRT. Both preparations similarly reduced climacteric complaints, whereas tibolone showed less breast complaints than ccHRT. CONCLUSION(S): This study confirms that tibolone, and to a lesser extent also ccHRT, changes hemostasis parameters toward a more fibrinolytic profile, which may diminish the risk of venous thrombosis.     

紧密连接在妊娠生理与病理生理中的作用

紧密连接（tight junction,TJ）主要由跨膜蛋白家族occludin,claudin以及膜周蛋白ZO家族等构成,存在于上皮细胞之间、上皮细胞与血管内皮细胞之间,负责调控细胞旁离子和溶质分子的跨膜运输及维持细胞极性状态,参与细胞分化增殖等重要生理功能,受到多种因素调节。研究显示,正常子宫内膜组织、胎盘组织以及黄体细胞中均有紧密连接结构和紧密连接相关因子的表达,紧密连接结构和功能异常可影响妊娠期子宫内膜容受性、胎盘植入及黄体功能,可能参与妊娠生理过程和妊娠病理生理的发生发展。因此,研究紧密连接在妊娠生理和病理中的作用具有重要的意义。     

Shedding of syncytiotrophoblast microvilli into the maternal circulation in pre-eclamptic pregnancies

Objective To investigate whether syncytiotrophoblast microvilli (STBM) are shed into the maternal circulation in increased amounts in pre-eclamptic pregnancies as a possible cause of maternal vascular endothelial dysfunction.
Design A time-resolved fluoroimmunoassay was developed to measure STBM levels in peripheral and uterine venous plasma from normal pregnant and pre-eclamptic women. Three colour flow cytometry was used to assess the microparticulate nature of the STBM in pregnancy plasma. The effects of these plasmas on endothelial cell proliferation was compared and a correlation with the levels of STBM detected was sought.
Setting A laboratory investigation using clinical samples obtained from an obstetric practice in a teaching hospital.
Samples Peripheral venous plasma from 20 women with established pre-eclampsia, 20 normal pregnant women matched for age, gestation and parity, and 10 nonpregnant women of reproductive age. Paired uterine and peripheral venous plasma taken at caesarean section from 10 women with pre-eclampsia and 10 unmatched normal pregnant women.
Results STBM were detected in the plasma of pregnant women by both flow cytometry and time-resolved fluoroimmunoassay. Significantly higher levels of STBM were found in women with established pre-eclampsia (   P = 0.01  ). STBM concentrations were higher in uterine venous plasma than in concurrently sampled peripheral venous plasma, confirming their placental origin. A significant correlation was found between the amount of STBM in the plasma and endothelial cell inhibitory activity.
Conclusions STBM are shed into the maternal circulation (microvillous deportation) and are present in significantly increased amounts in pre-eclamptic women. They may contribute to the endothelial dysfunction underlying the maternal syndrome of pre-eclampsia.     

Blood flow velocity waveforms in large maternal and uterine vessels throughout pregnancy and postpartum: a longitudinal study using Duplex sonography

Summary. Blood flow velocity waveforms in large maternal and uterine vessels were measured longitudinally from 16 weeks gestation onwards until 12 weeks postpartum in 21 singleton pregnancies by duplex sonography. In the maternal carotid artery, time average mean velocity (TAVmean) did not show significant changes. In both the femoral artery and vein, however, significant changes were observed. In the femoral artery, TAVmean and systolic maximum velocities decreased with advancing gestation. In the femoral vein, TAVmean remained constant throughout pregnancy and was lower than postpartum. The resistance index in the uterine arteries decreased with advancing gestation and increased after delivery. Among many factors contributing to femoral arterial blood flow velocity changes in pregnancy, we suggest that a major one is the increase in uterine blood flow. Reduction in venous femoral blood flow velocity and increase in the femoral vein diameter might be associated with the common occurrence of venous disorders in pregnancy.     

PIH is associated with an increase of trophoblasts circulating in maternal blood

One of the reason of PIH problems may be due to exposition to placental trophoblast. The objective of the work was to evaluate the number of trophoblast cells deported into maternal peripheral blood of patients with PIH (pregnancy induced hypertension) as compared to normal pregnancy. Trophoblasts have been detected, by cytofluorimetry, in peripheral maternal venous blood of hypertensive woman (15 cases) and normotensive pregnancy (16 cases). Women with PIH had statistically significant (p < 0.005) higher trophoblasts number than that found in normotensive pregnant women without PIH (16 cases). Our results indicate that the increased trophoblasts deportation into peripheral blood could be a marker of the maternal syndrome of PIH.