Excessive fibrinolysis detected with thromboelastography in a case of amniotic fluid embolism: fibrinolysis may precede coagulopathy

Journal of Thrombosis and Thrombolysis - Amniotic fluid embolism (AFE) is a catastrophic condition in the peripartum period and still remains as a leading cause of maternal death. Although over 80%...     

Unusual pulmonary embolism: septic pulmonary embolism and amniotic fluid embolism.

BACKGROUND: Septic and amniotic fluid emboli are rare sources of pulmonary embolism (PE), so the present study sought to elucidate the background of these cases. METHODS AND RESULTS: A total of 11,367 PE cases were identified from 396,982 postmortem examinations. The incidence of septic PE was 247 (2.2%) of the total. The origin of infection was found in 85.6% of the cases. Fungal embolus was detected more often than bacterial embolus. The most frequently detected fungus was aspergillus (20.8%). The primary disease associated with fungal embolus was leukemia (43.2%). The incidence of PE cases associated with pregnancy and/or delivery was 89 (0.8%) of the total PE cases. Among them, amniotic fluid embolism was found in 33 (73.3%) of 45 PE cases with vaginal delivery, and in 7 (21.2%) of 33 PE cases with cesarean delivery (p<0.0001). CONCLUSION: Fungal embolus was more frequent than bacterial embolus, and leukemia was most frequent as the primary disease in cases of fungal embolus. The main cause of PE in cesarean section cases was thrombotic embolism, and the main cause in vaginal delivery cases was amniotic fluid embolism.     

A case report of early application of veno-arterial extracorporeal membrane oxygenation in amniotic fluid embolism

Rationale:Amniotic fluid embolism (AFE) is a rare obstetrical complication and is a leading cause of maternal death in developed countries. Despite the development of supportive therapeutic measures, the mortality rate remains high.Patient concerns:A 38-year-old nulliparous pregnant woman, who underwent in vitro fertilization-embryo transfer, was admitted for labor at 37 weeks’ gestation. Approximately 30 minutes after delivery of the placenta, the puerpera developed postpartum hemorrhage with uterine atony. Soon after, the patient experienced hypotension, repeated cardiac arrest, refectory hypoxia, and disseminated intravascular coagulopathy.Diagnosis:AFE is diagnosed clinically. The pregnant woman in this case fulfilled the diagnostic criteria for AFE: acute hypotension, cardiac arrest, acute hypoxia, and coagulation disorders within approximately 30 minutes after delivery of the placenta.Interventions:The patient was intubated, connected to a ventilator, and was administered a high dose of vasoactive drugs to maintain blood pressure and underwent an emergency hysterectomy. Considering the risk for recurrent cardiac arrest and severe refractory hypoxia, venoarterial extracorporeal membrane oxygenation was initiated and discontinued as soon as cardiac function was restored based on serial bedside ultrasound assessment.Outcomes:The patient stabilized on day 7 in the intensive care unit and was transferred to the obstetrics ward and, 1 week later, was discharged with no complications. Two months later, follow-up revealed that the patient was in good condition.Lesson:Serial bedside ultrasound was crucial for assessing cardiac function and optimal weaning. Timely application of venoarterial extracorporeal membrane oxygenation and weaning was significant to avoid the occurrence of complications and improve long-term outcomes.     

Conjugated glucocorticoids in amniotic fluid and fetal lung maturation.

While recent studies suggest that cortisol plays a role in lung maturation, conflicting reports have recently appeared relating cortisol in amniotic fluid to indices of lung maturation. the variation in the levels and differences in correlation appear to be due to differences in methodology, principally with respect to cross-reactivity in the radioimmunoassays with the conjugates of cortisol and corticosterone. We have found that the glucocorticoid conjugates correlate better with lung maturation (rs = 0.79) than does cortisol itself (rs = 0.58). This is probably because the conjugates are derived exclusively from the fetal compartment whereas cortisol is also produced by the chorionic membrane. In anencephaly, conjugate levels were very low while cortisol levels were relatively normal. Conjugate levels (mainly sulfates) appear promising as an adjunct to tests of fetal maturation.     

Effect of intraamniotic fluid thyroxine injection on fetal serum and amniotic fluid iodothyronine concentrations.

Seven hundred micrograms of T4 were injected into the amniotic cavity 24 h before delivery of five pregnant women scheduled for elective cesarean section at term. T4, T3, and rT3 concentrations were measured by RIA in amniotic fluid obtained at the time of the injection and in amniotic fluid and cord serum samples collected at delivery. Iodothyronine concentrations also were determined on cord samples from 24 full term control infants. The geometric mean serum T4 concentration in the experimental infants was 27.2 micrograms/dl, almost 3 times that of the control population (10.3 micrograms/dl); serum rT3 concentrations were markedly elevated to a mean of 657 ng/dl, compared to 254 ng/dl in control infants. The mean serum T3 concentration was slightly but significantly increased to 61.3 ng/dl (control, 48.3 ng/dl; P less than 0.02). Amniotic fluid T4, T3, and rT3 concentrations all increased significantly. T4 injection into the amniotic fluid is an effective method of increasing fetal serum T4 concentrations. The preferential pathway of monodeiodination of the injected T4 in the human fetus is to rT3 rather than T3.     

Immunoassay of a somatomedin-binding protein from human amniotic fluid: levels in fetal, neonatal, and adult sera

We developed a specific RIA for a somatomedin (Sm)-binding protein, with an approximate mol wt of 35-40,000, purified from midgestational human amniotic fluid (AF) and termed AF-binding protein (AFBP). After Sephadex G-200 chromatography AFBP-RIA activity was found in fractions of fetal and cord serum only at a kav corresponding to a mol wt of +/- 40,000. Whole serum or plasma dilutions in a range of 1:20 to 1:600 showed parallelism with the standard curve. Sm-binding activity in fetal serum was found solely at a mol wt of 30-40,000; in cord serum additionally at a mol wt range of 150-200,000. AFBP serum or plasma concentrations determined by RIA were influenced by several factors: AFBP values in eight adults were highest in the morning (mean +/- SEM, 0.7 +/- 0.1 mu geq/ml) and lowest at night (0.3 +/- 0.1). AFBP values in pre- and postnatal serum showed a gradual decline with increasing age: fetal serum: mean +/- SEM, 36.7 +/- 15.7 (n = 17); adults: 0.6 +/- 0.07 mu geq/ml (n = 19). In serum from GH-deficient children AFBP concentrations were significantly higher than in an age-matched control group (P less than 0.05). Elevated values also were found in serum of children with end-stage renal failure and in serum of pregnant women at 36 weeks of gestation. AFBP was found in urine of preterm infants (mean +/- SEM, 0.04 +/- 0.005 mu geq/ml; n = 31). AFBP immunoreactivity was demonstrable in serum of three orangoutan mothers and their three children and in medium of a hepatoma cell line (PLC/PRF/5) but not in bovine, porcine, rabbit, or rat serum or in medium of cell cultures of (pre-)term placentae. We conclude that AFBP immunoreactivity is present in pre- and postnatal serum and has striking similarity to an unsaturated serum Sm-binding protein with a mol wt of +/- 40,000.     

Maternally administered melatonin differentially regulates lipopolysaccharide-induced proinflammatory and anti-inflammatory cytokines in maternal serum, amniotic fluid, fetal liver, and fetal brain

Lipopolysaccharide (LPS) has been associated with adverse developmental outcome, including intra-uterine fetal death and intra-uterine growth retardation. In the LPS model, tumor necrosis factor alpha (TNF-alpha) is the major mediator leading to intra-uterine fetal death and intra-uterine growth retardation. Interleukin (IL)-10 protects rodents against LPS-induced intra-uterine fetal death and intra-uterine growth retardation. Melatonin is an immunomodulator. In the present study, we investigated the effect of maternally administered melatonin on LPS-induced proinflammatory and anti-inflammatory cytokines in maternal serum, amniotic fluid, fetal liver and fetal brain. The time pregnant mice were injected with melatonin [5.0 mg/kg, intraperitoneal (i.p.)] 30 min before LPS (500 microg/kg, i.p.) on gestational day 17. As expected, TNF-alpha, IL-1beta, IL-6 and IL-10 were obviously increased in maternal serum and amniotic fluid in response to LPS. In addition, maternal LPS exposure significantly increased the levels of TNF-alpha, IL-1beta, IL-6 and IL-10 in fetal liver, and TNF-alpha and IL-10 in fetal brain. Melatonin pretreatment significantly attenuated LPS-evoked elevation of TNF-alpha in maternal serum. On the contrary, melatonin aggravated LPS-induced increase in IL-10 in maternal serum. Melatonin had no effect on LPS-evoked IL-1beta and IL-6 in maternal serum and amniotic fluid. Interestingly, maternally administered melatonin also significantly attenuated LPS-evoked elevation of TNF-alpha in fetal brain, whereas the indole aggravated LPS-induced increase in IL-10 in fetal liver. Taken together, these results indicate that maternally administered melatonin differentially regulates LPS-induced proinflammatory and anti-inflammatory cytokines in maternal serum, amniotic fluid, fetal liver, and fetal brain.     

羊水栓塞患者20例首发症状及母体结局的回顾性分析

目的探讨羊水栓塞患者首发症状与母体结局的关系。方法回顾分析2000-01~2014-08该院接诊的20例羊水栓塞患者的首发症状及母体结局的关系。结果 12例以剖宫产术中或产后弥散性血管内凝血为首发症状,其中3例死亡;5例以抽搐为首发症状,其中2例死亡;1例以昏迷为首发症状,死亡;2例以心跳骤停为首发症状患者均死亡。结论以心跳骤停、昏迷或抽搐为首发症状的羊水栓塞相对弥散性血管内凝血为首发症状的羊水栓塞更凶险,母体预后不良。     

Daily hormonal changes in the maternal, fetal, and amniotic fluid compartments before parturition in a primate species

The daily hormonal fluctuations that occur simultaneously in the fetus, mother, and amniotic fluid during late gestation and before preterm parturition were studied in long term catheterized rhesus macaques. Blood and amniotic fluid samples were collected twice daily and analyzed by RIA for estrone, estradiol, dehydroepiandrosterone sulfate (DHEAS), progesterone, cortisol, and prostaglandin F2 alpha metabolite (PGFM). Vaginal delivery in monkeys with live fetuses was preceded by rising concentrations of DHEAS in fetal, but not maternal, blood. Parallel increases in fetal plasma estrone, maternal plasma estrone and estradiol, and amniotic fluid estrone preceded the rise in amniotic fluid PGFM (P less than 0.005, by analysis of variance). Cortisol levels remained stable in maternal blood and amniotic fluid, but increased before delivery in fetal blood. Nocturnal progesterone peaks in both fetal and maternal blood increased progressively in magnitude in fetuses before parturition. Rising concentrations of fetal DHEAS, estrone, and progesterone indicated an increase in adrenal activity before parturition in the rhesus fetus. PG production, reflected in amniotic fluid PGFM concentrations, was temporally related to increasing amniotic fluid concentrations of estrone. Although progesterone withdrawal may occur at a local tissue level, parturition occurred without an apparent decrease in circulating maternal, circulating fetal, or amniotic fluid progesterone concentrations.     

Infection in pregnancy as a causal factor in premature membrane rupture and preterm labor

This article discusses recent evidence pointing to an infectious etiology of premature rupture of the membranes and preterm labor. We conclude that antepartum infection is strongly related to preterm labor, premature rupture of the membranes and perinatal morbidity and mortality.     

The effects of fetal energy depletion on amniotic fluid concentrations of amino acids,organic acids and related metabolites

Summary Concentrations of amino and organic acids, phosphate, sulphate, gluconic acid and gluconolactone were measured in amniotic fluid samples which contained either normal or raised hypoxanthine concentrations. In this way, the effect of mild fetal ATP depletion could be determined.The effects of this mild asphyxia were to raise concentrations of phenylalanine, tyrosine, lysine, glycine, phosphate, sulphate, gluconic acid and glucono-1,5-lactone. However, concentrations of a variety of other metabolites were unchanged; thus no diagnostic confusion should arise with organic acidurias in mild asphyxia in contrast to the biochemical mimickry produced by severe asphyxia. Since clinically normal parturition can produce changes in amniotic fluid, urine from newborn or cord blood may not reflect the metabolic balancein utero.     

Prenatal diagnosis of vitamin D-dependent rickets, type II: response to 1,25-dihydroxyvitamin D in amniotic fluid cells and fetal tissues

Vitamin D-dependent rickets type II (VDDR-II; hereditary resistance to 1,25-dihydroxyvitamin D3 [1,25(OH)2D3]), an autosomal recessive genetic disease that results from a failure to respond to 1,25-(OH)2D3, is characterized by severe rickets, hypocalcemia, growth retardation, and high prevalence of alopecia. We used amniotic fluid cells in the 17th week of gestation to detect VDDR-II in fetuses at risk for the defect. First, we demonstrated in cells obtained from 15 control pregnancies the presence of a specific high affinity 1,25-(OH)2D3 receptor (Kd = 0.3 x 10(-11) mol/L; maximal number of binding sites, 6.1 fmol/mg protein) and 1,25-(OH)2D3-induced 25-hydroxyvitamin D3-24-hydroxylase activity (up to 30-fold increase). Amniotic fluid cells from a woman who had already given birth to a child with VDDR-II contained receptors that bound [3H]1,25-(OH)2D3 normally and responded to 1,25-(OH)2D3 stimulation with a 10-fold increase in 24-hydroxylase activity. The fetus was, therefore, judged unaffected, and a normal baby girl was born. At the age of 16 months she did not demonstrate clinical or biochemical features of VDDR-II. Amniotic fluid cells from another mother of a child with VDDR-II were unable to bind [3H]1,25-(OH)2D3, and the hormone failed to stimulate 24-hydroxylase activity. VDDR-II in this fetus was confirmed after termination of pregnancy by the total inability of 1,25-(OH)2D3 to stimulate 24-hydroxylase activity in tissue explants and cell cultures prepared from the fetus's kidney and skin. In contrast, tissues from dead control fetuses responded to stimulation by 1,25-(OH)2D3 with a 3- to 10-fold increase in 24-hydroxylase activity. Fetal kidney and skin explants and cell cultures also synthesized a [3H]1,25-(OH)2D3-like metabolite from [3H]25-OHD3 as early as the 17th week of gestation. 1,25-(OH)2D3 (10 nM) decreased the in vitro synthesis of the [3H]1,25-(OH)2D3-like metabolite in tissues from dead control fetuses, but not from the affected fetus. Thus, human fetuses at midgestation already have the regulatory mechanisms responsive to 1,25-(OH)2D3 present postnatally. The prenatal diagnosis of VDDR-II is now possible and is indicated in a high risk family.     

Catheter-directed,ultrasound-facilitated fibrinolysis in obese patients with massive and submassive pulmonary embolism

Obesity is a well-established risk factor for pulmonary embolism (PE). However, treatment of PE in obese patients is challenging because of limited outcomes data, especially with advanced therapies such as catheter-based fibrinolysis. We assessed the efficacy and safety of ultrasound-facilitated, catheter-directed fibrinolysis in obese patients with submassive and massive PE enrolled in the SEATTLE II Trial. Eligible patients had a right ventricular-to-left ventricular (RV/LV) diameter ratio?≥?0.9 on chest computed tomography (CT). The primary efficacy outcome was the change in chest CT-measured RV/LV diameter ratio at 48 h after procedure initiation. The primary safety outcome was GUSTO major bleeding within 72 h. One-hundred and four patients were obese, as defined by a BMI?≥?30 kg/m², and 44 were non-obese. Mean RV/LV ratio was greater in obese patients at baseline compared with non-obese patients (1.60 vs. 1.43, p?=?0.02). Reduction in RV/LV diameter ratio at 48 h was greater in obese patients compared with non-obese patients (absolute reduction: ??0.47 vs. ??0.30, p?=?0.01; relative reduction: ??26 vs. ??18%, p?=?0.03). Major bleeding occurred in 12 (12%) of obese patients and in 3 (7%) in non-obese patients (p?=?0.55). In conclusion, ultrasound-facilitated, catheter-directed fibrinolysis shows promise in obese patients for whom advanced therapy for acute PE is warranted.     

Two immunoreactive binding proteins for insulin-like growth factors in human amniotic fluid: relationship to fetal maturity

A binding protein for insulin-like growth factors (IGFs) has been purified from human amniotic fluid by IGF-I affinity chromatography and high performance reverse phase chromatography. This protein, with an apparent molecular mass of 28K nonreduced and 34K reduced, had an identical amino-terminus to a previously purified binding protein from amniotic fluid and to placental protein 12. The purified preparation (BP-28) bound both IGFs with high affinity [Ka, 6.55 +/- 2.24 (+/- SD) L/nmol for IGF-I and 3.23 +/- 1.05 L/nmol for IGF-II], with approximately 0.5 mol binding sites/mol BP-28 for either ligand. A 53K IGF-binding protein purified from human plasma (BP-53) did not cross-react in a RIA for BP-28, and BP-28 had less than 0.1% molar cross-reactivity in a RIA for BP-53. Human amniotic fluid reacted strongly in both assays. Fractionation of amniotic fluid samples by reverse phase chromatography showed that BP-28 and BP-53 immunoreactivities were present on separate proteins. In 40 third trimester amniotic fluid samples selected to cover a wide range of lecithin to sphingomyelin ratios, the mean concentrations of BP-28 and BP-53 were 37.6 +/- 17.6 (+/- SD) and 4.6 +/- 1.6 mg/L, respectively. Significant negative correlations were found between the levels of both BP-28 and BP-53 and the lecithin to sphingomyelin ratio, suggesting an association between the levels of both proteins and the degree of fetal maturity. A significant positive association was also found between the levels of BP-28 and BP-53. We conclude that the 28K IGF-binding protein from amniotic fluid, like the previously purified 53K binding protein, has high affinity for both IGF-I and IGF-II, that it coexists in amniotic fluid with BP-53 or a related protein, and that the levels of both proteins decline with increasing fetal maturity.     

Factor IX and prothrombin in amniotic fluid and fetal plasma: constraints on prenatal diagnosis of hemophilia B and evidence of proteolysis

Potential limitations of prenatal diagnosis of hemophilia B, as compared to hemophilia A, include (1) occurrence of far more frequent defects with abnormal circulating antigen, (2) lower levels of factor IX in fetal plasma at 16 to 20 weeks gestation, and (3) the presence of factor IX antigen in amniotic fluid. In addition, proteolysis could occur, especially with amniotic fluid contamination of fetal plasma. A sensitive polyclonal immunoradiometric assay for factor IX antigen was used to characterize the range of levels in amniotic fluids and fetal plasma samples. To assess for altered forms, factor IX species were compared to those of a homologous clotting factor, prothrombin. Fourteen postmortem abortus blood samples from fetuses of 14 to 23 weeks gestation had factor IX antigen levels that averaged 5.1 U/dL and ranged from 1.7 to 15 U/dL. Amniotic fluid factor IX antigen averaged 2.9 U/dL, with a range from 1.4 to 8.5 U/dL in 19 separate amniocentesis samples. Thus, in a male fetus at risk of hemophilia B and with a low circulating level of gene product, mixture of fetal plasma with amniotic fluid could severely limit prenatal diagnosis, assuming that the amniotic fluid factor IX is of maternal origin. Despite rapid processing of amniotic fluid samples, the prothrombin was extensively cleaved, suggesting that it had been activated in vivo. On gel electrophoresis of amniotic fluid samples, however, factor IX was only minimally cleaved. In the postmortem fetal blood specimens, prothrombin was partially cleaved. On crossed-immunoelectrophoresis, fetal plasma prothrombin showed decreased migration in calcium, compared to EDTA, indicative of mature gamma-glutamyl carboxylation. The latter presumably resulted from fetal hepatic synthesis.