fibrin and Pre-Eclampsia

Preeclampsia is a devastating medical complication of pregnancy that can lead to significant maternal and fetal morbidity and mortality. It is currently believed that there is abnormal placentation in as early as the first trimester in women destined to develop preeclampsia. Although the etiology of the abnormal placentation is being debated, numerous epidemiologic and experimental studies suggest that imbalances in circulating angiogenic factors released from the placenta are responsible for the maternal signs and symptoms of preeclampsia. In particular, circulating levels of soluble fms-like tyrosine kinase 1, an antiangiogenic factor, are markedly increased in women with preeclampsia, whereas free levels of its ligand, placental, growth factor are markedly diminished. Alterations in these angiogenic factors precede the onset of clinical signs of preeclampsia and correlate with disease severity. Recently, the availability of automated assays for the measurement of angiogenic biomarkers in the plasma, serum, and urine has helped investigators worldwide to demonstrate a key role for these factors in the clinical diagnosis and prediction of preeclampsia. Numerous studies have reported that circulating angiogenic biomarkers have a very high negative predictive value to rule out clinical disease among women with suspected preeclampsia. These blood-based biomarkers have provided a valuable tool to clinicians to accelerate the time to clinical diagnosis and minimize maternal adverse outcomes in women with preeclampsia. Angiogenic biomarkers have also been useful to elucidate the pathogenesis of related disorders of abnormal placentation such as intrauterine growth restriction, intrauterine fetal death, twin-to-twin transfusion syndrome, and fetal hydrops. In summary, the discovery and characterization of angiogenic proteins of placental origin have provided clinicians a noninvasive blood-based tool to monitor placental function and health and for early detection of disorders of placentation. Uncovering the mechanisms of altered angiogenic factors in preeclampsia and related disorders of placentation may provide insights into novel preventive and therapeutic options.

Topics: Biomarkers; Bronchopulmonary Dysplasia; Cardiovascular Diseases; Female; Fetal Death; Fetofetal Transfusion; Fibrin; Humans; Hydrops Fetalis; Placenta Diseases; Placenta Growth Factor; Placentation; Pre-Eclampsia; Pregnancy; Prognosis; Puerperal Disorders; Up-Regulation; Vascular Endothelial Growth Factor A; Vascular Endothelial Growth Factor Receptor-1

Preeclampsia evolves in 2 stages: a placental problem that generates signals to the mother to cause a range of responses that comprise the second stage (preeclampsia syndrome). The first stage of early-onset preeclampsia is poor placentation, which we here call malplacentation. The spiral arteries are incompletely remodeled, leading to later placental malperfusion, relatively early in the second half of pregnancy. The long duration of the first stage (several months) is unsurprisingly associated with fetal growth restriction. The first stage of late-onset preeclampsia, approximately 80% of total cases, is shorter (several weeks) and part of a process that is common to all pregnancies. Placental function declines as it outgrows uterine capacity, with increasing chorionic villous packing, compression of the intervillous space, and fetal hypoxia, and causes late-onset clinical presentations such as "unexplained" stillbirths, late-onset fetal growth restriction, or preeclampsia. The second stages of early- and late-onset preeclampsia share syncytiotrophoblast stress as the most relevant feature that causes the maternal syndrome. Syncytiotrophoblast stress signals in the maternal circulation are probably the most specific biomarkers for preeclampsia. In addition, soluble fms-like tyrosine kinase-1 (mainly produced by syncytiotrophoblast) is the best-known biomarker and is routinely used in clinical practice in many locations. How the stress signals change over time in normal pregnancies indicates that syncytiotrophoblast stress begins on average at 30 to 32 weeks' gestation and progresses to term. At term, syncytiotrophoblast shows increasing markers of stress, including apoptosis, pyroptosis, autophagy, syncytial knots, and necrosis. We label this phenotype the "twilight placenta" and argue that it accounts for the clinical problems of postmature pregnancies. Senescence as a stress response differs in multinuclear syncytiotrophoblast from that of mononuclear cells. Syncytiotrophoblast irreversibly acquires part of the senescence phenotype (cell cycle arrest) when it is formed by cell fusion. The 2 pathways converge on the common pathologic endpoint, syncytiotrophoblast stress, and contribute to preeclampsia subtypes. We highlight that the well-known heterogeneity of the preeclampsia syndrome arises from different pathways to this common endpoint, influenced by maternal genetics, epigenetics, lifestyle, and environmental factors with different fetal and matern

Topics: Apoptosis; Autophagy; Cellular Senescence; Extracellular Vesicles; Female; Fibrin; Humans; Necrosis; Placentation; Pre-Eclampsia; Pregnancy; Stress, Physiological; Trophoblasts

Preeclampsia (PE) is a multi-system disorder of human pregnancy characterized by hypertension and proteinuria. Although its pathogenesis is not fully understood, predisposition to endothelial dysfunction is thought to play a crucial part. Normotensive pregnancy is associated with increases in coagulation factor levels and decreases in natural anticoagulation, leading to a hypercoagulable state. This state is thought to be part of a complex physiological adaptation, which ensures rapid and effective control of bleeding from the placental site at the time of placental separation. In PE, a more pronounced exacerbation of the hypercoagulable state is noticed, compared to normotensive pregnancy. Activation of coagulation in PE occurs at an early stage of the disease and often antedates the clinical symptoms. It is known that PE is associated with fibrin deposition in the kidney glomerulus, and in fatal cases, widespread fibrin deposition has been a prominent histological finding. Related to the fibrinolytic system in PE, the state of the art allows the assumption that blood coagulation overlaps the fibrinolytic regulatory mechanism, since fibrin deposition in maternal microcirculation is usually found in PE. However, there is still no consensus about its specific role. This review aims to discuss the fibrinolytic system in PE and its potential implications to the pathogenesis of this disease.

Topics: Female; Fibrin; Fibrinolysis; Humans; Kidney; Pre-Eclampsia; Pregnancy

In balance, available studies employing sophisticated coagulation assays demonstrate enhanced thrombin generation in women with preeclampsia. The etiology is unknown but likely stems from the damage of vascular endothelium. Although activation of the clotting cascade does not cause preeclampsia, it likely contributes to the manifestations by obstruction and trauma of the microvasculature. Markers of clotting cascade activation such as AT III may be useful in the hypertensive preterm patient in whom the diagnosis is unclear.

Topics: Antithrombin III; Blood Coagulation Disorders; Blood Platelets; Factor VIII; Female; Fetal Blood; Fibrin; Glycoproteins; Humans; Pre-Eclampsia; Pregnancy; Protein C; Protein S

Topics: Abortion, Habitual; Animals; Antibodies; Antigen-Antibody Complex; Antigens; Blood Vessels; Choriocarcinoma; Complement System Proteins; Female; Fetus; Fibrin; Fibrinogen; Histocompatibility; Histocytochemistry; HLA Antigens; Humans; Immunoglobulins; Placenta; Pre-Eclampsia; Pregnancy; Pregnancy Complications; Pregnancy in Diabetics; Uterine Neoplasms; Uterus

Ultrastructural study of the placental bed spiral arteries confirms that non-villous cytotrophoblast is involved in the development of the physiological changes occurring in these vessels during normal pregnancy. The changes observed in the myometrial segments of the spiral arteries before the time of arrival of endovascular trophoblast but after the invasion of the myometrium by migrating interstitial trophoblast, are characterised by widening of the lumen, oedema of the intima, disruption of the elastica and widening of the intercellular spaces of the media. This vascular distension could facilitate the subsequent retrograde migration of endovascular trophoblast. The fetal cells migrate in the vessel lumen and infiltrate the subendothelial space causing further disruption of the arterial intima and media. The altered intima is subsequently recovered by the endothelium. In this way, the cytotrophoblast is incorporated into the wall of the placental bed spiral arteries which are converted from small muscular arteries into distended hyalinized tubes. In pregnancies complicated by preeclampsia and in some pregnancies complicated by fetal growth retardation, these physiological changes are largely restricted to the decidual segments leaving the myometrial segments unaffected. The lesion of acute atherosis is characterised by thickening of the intima and necrosis of the media. The intimal thickening is due to deposition of fibrin and other plasma constituents and migration into the intima of macrophages and myointimal cells which accumulate fat in their cytoplasm to become foam cells. Clinical and experimental studies indicate that these lesions can be initiated by several factors which cause endothelial injury.

Topics: Arteries; Arteriosclerosis; Endothelium; Female; Fetal Growth Retardation; Fibrin; Humans; Microscopy, Electron; Placenta; Pre-Eclampsia; Pregnancy; Pregnancy Complications, Cardiovascular; Trophoblasts; Uterus

1. The lack of a general agreement on the definition of PE makes the interpretation of laboratory findings in different series of these patients difficult. 2. Thrombocytopenia is the most common hemostatic abnormality in patients with PE and is caused by platelet consumption. 3. There is little concrete evidence that thrombin mediates the thrombocytopenia in most of these patients. 4. Immune mechanisms or severe vasospasm with resultant endothelial damage may contribute to the thrombocytopenia in some patients.

Topics: Anemia, Hemolytic; Disseminated Intravascular Coagulation; Eclampsia; Epoprostenol; Factor VIII; Female; Fibrin; Fibrin Fibrinogen Degradation Products; Fibrinogen; Fibrinopeptide A; Humans; Hypertension; Platelet Count; Pre-Eclampsia; Pregnancy; Pregnancy Complications, Hematologic; Thrombin; Thrombocytopenia; Thromboxane A2

Topics: Arachidonic Acids; Arteriosclerosis; Aspirin; Blood Platelets; Calcium; Coronary Disease; Cyclic AMP; Diabetes Mellitus; Dietary Fats; Female; Fibrin; Humans; Myeloproliferative Disorders; Nephrotic Syndrome; Oxygenases; Platelet Adhesiveness; Platelet Aggregation; Pre-Eclampsia; Pregnancy; Prostaglandins; Thrombosis

Topics: Animals; Blood Cell Count; Blood Coagulation; Blood Coagulation Tests; Blood Platelets; Disseminated Intravascular Coagulation; Eclampsia; Female; Fibrin; Fibrin Fibrinogen Degradation Products; Fibrinogen; Fibrinolysis; Hemostasis; Heparin; Humans; Hypertension; Placental Insufficiency; Pre-Eclampsia; Pregnancy

Topics: Acute Kidney Injury; Animals; Blood Coagulation; Child; Disseminated Intravascular Coagulation; Female; Fibrin; Fibrinolysis; Glomerulonephritis; Graft Rejection; Hemolytic-Uremic Syndrome; Heparin; Humans; Kidney Diseases; Kidney Glomerulus; Kidney Transplantation; Mice; Phagocytosis; Pre-Eclampsia; Pregnancy; Rabbits; Transplantation, Homologous

Topics: Abruptio Placentae; Blood Coagulation; Blood Coagulation Disorders; Blood Coagulation Factors; Blood Coagulation Tests; Blood Platelet Disorders; Blood Transfusion; Disseminated Intravascular Coagulation; Embolism, Amniotic Fluid; Factor XIII Deficiency; Female; Fetal Death; Fetal Diseases; Fibrin; Fibrinogen; Fibrinolysis; Hemophilia A; Humans; Liver Diseases; Pre-Eclampsia; Pregnancy; Pregnancy Complications, Hematologic; Sepsis; Uterine Hemorrhage; Vitamin K

Topics: Animals; Blood Coagulation; Blood Coagulation Tests; Brain; Capillaries; Disseminated Intravascular Coagulation; Eclampsia; Female; Fibrin; Heparin; Humans; Kidney Cortex Necrosis; Kidney Glomerulus; Liver; Placenta; Platelet Adhesiveness; Pre-Eclampsia; Pregnancy; Pregnancy Complications, Hematologic

Topics: Acute Kidney Injury; Angiotensin II; Animals; Anticoagulants; Blood Coagulation; Blood Coagulation Disorders; Catecholamines; Disseminated Intravascular Coagulation; Female; Fibrin; Heparin; Humans; Hypertension, Renal; Kidney Diseases; Kidney Glomerulus; Pre-Eclampsia; Pregnancy; Renin; Thrombosis; Uremia

Topics: Abruptio Placentae; Adrenal Glands; Aminocaproates; Animals; Basement Membrane; Biopsy; Blood Coagulation Disorders; Blood Coagulation Factors; Blood Platelets; Brain; Female; Fibrin; Fibrinogen; Fibrinolysis; Fluorescent Antibody Technique; Hemorrhage; Hemorrhagic Disorders; Heparin; Humans; Hypertension, Malignant; Kidney Cortex Necrosis; Kidney Failure, Chronic; Kidney Glomerulus; Liver; Maternal Mortality; Microscopy, Electron; Myocardium; Placental Extracts; Pre-Eclampsia; Pregnancy; Rabbits; Shwartzman Phenomenon; Thromboplastin; Thrombosis

Topics: Autoimmune Diseases; Biopsy; Blood Coagulation Disorders; Blood Protein Electrophoresis; Diagnosis, Differential; Female; Fibrin; Fibrinogen; Fluorescent Antibody Technique; gamma-Globulins; Glomerulonephritis; Humans; Immunoelectrophoresis; Kidney; Kidney Diseases; Kidney Glomerulus; Pre-Eclampsia; Pregnancy

; Early-onset preeclampsia is a rare pregnancy-specific disorder associated with significantly increased maternal and fetal morbidity and mortality. Whilst it is known that even normotensive pregnancies are associated with changes in clot formation and dissolution, the nature of how these changes differ in those with early onset preeclampsia has not been well established. We sought to evaluate parameters of fibrin formation and fibrinolysis in individuals with early onset preeclampsia in comparison to both pregnant and non-pregnant controls. Furthermore, such parameters were correlated with markers of disease severity in this patient cohort, including the presence of multiorgan involvement, the rate of disease progression and the extent of the anti-angiogenic state in this condition.. ; Patients with early onset preeclampsia (N = 20) and both pregnant (N = 16) and non -pregnant (N = 16) controls were recruited from the cohort at a large urban maternity hospital which saw over 15,000 deliveries during the study period. Platelet poor plasma was prepared from collected whole blood and analysed for parameters of fibrin formation and fibrinolysis (lagtime to and rate of fibrin formation; PAI-1; PAI-2; D-dimer; plasmin-antiplasmin; tPA) in addition to markers of angiogenesis (sFLT-1; Endoglin) using commercially available specific immunoassays.. ; The maximum rate of fibrin formation as well as PAI-1, PAI-2 and D-dimer levels were all significantly increased in those with early onset preeclampsia and pregnant controls when compared to non-pregnant controls without significant differences between the 2 former groups. Plasmin-antiplasmin levels were significantly reduced in a similar manner. tPA levels were significantly elevated in EOP compared to both pregnant and non-pregnant controls. EOP was associated with significantly increased anti-angiogenic factors (sFLT-1; Endoglin) when compared to both pregnant and non-pregnant controls.. ; Markers of fibrin formation and fibrinolysis are significantly alerted in early onset preeclampsia; furthermore, certain markers correlate with disease severity in this patient cohort.

Topics: Adult; Case-Control Studies; Female; Fibrin; Fibrinolysis; Humans; Pre-Eclampsia; Pregnancy

Preeclampsia is a pregnancy-specific syndrome characterized by placental dysfunction and an angiogenic imbalance. Systemically, levels of thrombomodulin, an endothelium- and syncytiotrophoblast-bound protein that regulates coagulation, inflammation, apoptosis, and tissue remodeling, are increased. We aimed to investigate placental thrombomodulin dysregulation and consequent downstream effects in the pathogenesis of preeclampsia.. Placentas from 28 preeclampsia pregnancies, 30 uncomplicated pregnancies, and 21 pregnancies complicated by growth restriction as extra controls were included. Immunohistochemical staining of thrombomodulin, caspase-3, and fibrin was performed. Placental mRNA expression of thrombomodulin, inflammatory markers, matrix metalloproteinases 2 and 9, and soluble Flt-1 were measured with quantitative polymerase chain reaction. Thrombomodulin mRNA expression was determined in vascular endothelial growth factor-transfected trophoblast cell lines. Thrombomodulin protein and mRNA expression were decreased in preeclampsia as compared with both control groups (P=0.001). Thrombomodulin mRNA expression correlated with maternal body mass index (P<0.01) and diastolic blood pressure (P<0.05) in preeclampsia. An increase in placental apoptotic cells was associated with preeclampsia (P<0.001). Thrombomodulin expression correlated positively with matrix metalloproteinase expression (P<0.01) in preeclampsia, but not with fibrin deposits or inflammatory markers. Placental soluble Flt-1 expression correlated with decreased thrombomodulin expression. Vascular endothelial growth factor induced upregulation of thrombomodulin expression in trophoblast cells.. Decreased thrombomodulin expression in preeclampsia may play a role in placental dysfunction in preeclampsia and is possibly caused by an angiogenic imbalance. Hypertension and obesity are associated with thrombomodulin downregulation. These results set the stage for further basic and clinical research on thrombomodulin in the pathogenesis of preeclampsia and other syndromes characterized by endothelial dysfunction.

Topics: Adult; Apoptosis; Caspase 3; Cell Line; Down-Regulation; Female; Fibrin; Humans; Inflammation Mediators; Matrix Metalloproteinases; Placenta; Pre-Eclampsia; Pregnancy; RNA, Messenger; Signal Transduction; Thrombomodulin; Transfection; Trophoblasts; Vascular Endothelial Growth Factor A; Vascular Endothelial Growth Factor Receptor-1

We present a case of a 39-year-old, gravida 3 para 2, Chinese female with a history of inherited type 1 Antithrombin deficiency and multiple prior episodes of venous thromboembolism. She presented at 29+4 weeks' gestation with severe pre-eclampsia complicated by haemolysis, elevated liver enzymes and low platelet (HELLP) syndrome. She subsequently underwent an emergency caesarean section for non-reassuring fetal status, which was complicated by postpartum haemorrhage secondary to uterine atony, requiring a B-Lynch suture intraoperatively.

Topics: Adult; Cesarean Section; China; Female; Fibrin; HELLP Syndrome; Humans; Pre-Eclampsia; Pregnancy; Uterine Inertia; Venous Thromboembolism

In the setting of preeclampsia (PE), decidual vasculopathy (DV) can be seen along the free membranes.. We describe DV using stains for CD31, CD34, Cd42b, CD68, desmin, fibrin and Masson's trichrome in patients with preeclampsia and fetal growth restriction.. We first examined the "membrane roll" sections from the placentas of six patients with preeclampsia. Affected vessels showed endothelial proliferation with detachment. Remodeling of the media was characterized by smooth muscle loss with variable degrees of fibrin deposition. CD31 and CD34 highlighted the prominent endothelium and showed striking particulate staining throughout the media. All of these findings infer a sequence of endothelial injury, fragmentation and repair with incorporation of endothelial components into the vascular wall. We evaluated the frequency of DV by clinical presentation; in cases with PE with and without small for gestational age (SGA) (N = 15), and SGA with and without Doppler flow abnormalities (N = 15). All groups except the SGA without Doppler abnormalities showed DV. Among placentas with DV, the most severely affected group was PE with SGA; the least affected was PE without SGA.. The association with SGA suggests that the DV is a subacute process of vascular injury that accelerates in the setting of PE. The majority of DV cases were not initially recognized suggesting a role for endothelial markers for DV detection. We also propose that the rampant endothelial injury seems to be a prominent finding in the decidual vessels of subjects with PE complicated by SGA and a similar process in the systemic vasculature may be responsible for the circulating endothelial microparticles reported in such patients.

Topics: Antigens, CD; Antigens, CD34; Antigens, Differentiation, Myelomonocytic; Decidua; Desmin; Female; Fetal Growth Retardation; Fibrin; Humans; Neovascularization, Pathologic; Placenta; Platelet Endothelial Cell Adhesion Molecule-1; Platelet Glycoprotein GPIb-IX Complex; Pre-Eclampsia; Pregnancy; Vascular Diseases

A common haplotype M2 consisting of minor SNP alleles located in the ANXA5 gene promoter region has been described as a risk factor for various obstetric complications such as recurrent pregnancy loss, pre-eclampsia and pregnancy-related thrombophilic disorder. However, the question of whether it is the maternal or fetal genotype that contributes to the onset of these disorders remains to be resolved.. We analyzed ANXA5 gene variants in the blood and placental tissues from pre-eclampsia patients and normotensive controls. ANXA5 expression was examined by qRT-PCR, Western blotting and immunostaining. Results were compared between M2 and non-M2 carriers.. The M2 haplotype was found to be significantly frequent in placentas from pre-eclamptic patients relative to the controls (25.5% versus 10%, P = 0.044), In contrast, no significant differences were observed in maternal blood (13.0% versus 11.3%, P = 0.597). The placental expression of ANXA5 mRNA was found to be lower in M2 carriers. When examined by Western blot and immunostaining, the ANXA5 protein levels were found to be affected more by the placental than the maternal genotype. Histological examination of the placentas from the pre-eclamptic patients demonstrated that a placental M2 haplotype correlated more closely than maternal M2 with the severity of perivillous fibrin deposition.. Although preliminary, these results suggest that hypomorphic M2 alleles in the in placental ANXA5 promoter, whether transmitted maternally or paternally, might be an essential determinant of an increased risk of pre-eclampsia via local thrombophilia at the feto-maternal interface.

Topics: Adult; Alleles; Annexin A5; Case-Control Studies; Cesarean Section; Chorionic Villi; Down-Regulation; Female; Fetus; Fibrin; Genetic Association Studies; Heterozygote; Humans; Japan; Placenta; Polymorphism, Genetic; Pre-Eclampsia; Pregnancy; Promoter Regions, Genetic; Risk; Severity of Illness Index; Surface Properties

Preeclampsia is a major cause of maternal and neonatal morbidity and mortality. In mouse models, complement activation in the placenta is associated with abnormal placental development and miscarriage, and inhibiting complement prevents fetal injury. We mated two mouse strains, DBA/2 and CBA/J, expecting that the pregnancies might show features of preeclampsia and of immunologically mediated pregnancy loss. Along with placental dysfunction, these matings resulted in proteinuria, elevated BUN, fibrin deposition, and glomerular endotheliosis. We blocked placental complement activation throughout pregnancy by administering a single dose of the C3 inhibitor CR2-Crry given on day 5 of the pregnancy. This procedure specifically targets the sites of complement activation without inducing any systemic effects. Placental complement inhibition prevented oxidative stress and placental dysfunction, as well as proteinuria and renal pathologic features of preeclampsia. Thus, local blockade of complement activation at the maternal-fetal interface rescues preeclampsia in mice, and identifies new treatments. Hence, complement triggers a feed-forward cycle of placental damage, antiangiogenic factor production, and maternal vascular damage in patients.

Topics: Animals; Blood Urea Nitrogen; Complement Activation; Disease Models, Animal; Female; Fibrin; Injections, Intravenous; Kidney; Mice; Mice, Inbred BALB C; Mice, Inbred CBA; Mice, Inbred DBA; Neovascularization, Physiologic; Oxidative Stress; Placenta; Pre-Eclampsia; Pregnancy; Proteinuria; Recombinant Fusion Proteins; Vascular Endothelial Growth Factor A; Vascular Endothelial Growth Factor Receptor-1

To define composition of chorionic plate and test effects of pre-eclampsia on basal plate composition.. Retrospective cohort study where distinct area fractions were measured in: healthy term chorionic plate (CP: n = 11), healthy placental basal plate (n = 11), mild pre-eclamptic basal plate (n = 10) and severe pre-eclamptic basal plate (n = 11).. CP lining is partly endothelial. Mean anchoring villus (AV)/acellular (NS) basal plate area ratio decreased in pre-eclampsia (p = 0.048). There was a decreasing trend with increasing disease severity. Basal plate endothelial cell proportion was not significantly lower in severe pre-eclampsia than in healthy or mild pre-eclamptics.. An inverse relationship between the proportions of fibrin and anchoring villi indicates that increased basal plate fibrin deposition and reduced basal plate materno-fetal anchoring area are part of pre-eclamptic disease progression. Endothelium lining intervillous surfaces may originate from circulating maternal endothelial progenitor cells.

Topics: Adolescent; Adult; Chorionic Villi; Cohort Studies; Female; Fibrin; Humans; Infant, Newborn; Pre-Eclampsia; Pregnancy; Retrospective Studies; Term Birth; Young Adult

Preeclampsia (PE) is a placenta-mediated pregnancy complication that results in high maternal and neonatal mortality and morbidity worldwide. Currently, there is no satisfactory pharmacotherapeutic treatment to stop the PE progression. In this study, we investigated the therapeutic effects of anticoagulant agents, including annexin V, heparin, and a fusion protein of annexin V and hirudin (AND), in a murine PE model induced by intravenous injection of phosphatidylserine/phosphatidylcholine (PS/PC) microvesicles. Compared with the control pregnant animals, the pregnant mice injected with PS/PC presented PE-like symptoms, including elevated systolic blood pressure, proteinuria, and reduction of antithrombin III and blood platelets. However, the PE-like symptoms were significantly alleviated after the PS/PC-injected mice were treated with annexin V, AND, or heparin. Furthermore, fibrin deposition in the placentas in the anticoagulant treated mice was remarkably improved, compared with that in the mice injected with PS/PC alone. The data demonstrate that anticoagulants are effective to prevent the occurrence of PE in the murine model and also suggest that hypercoagulation in the placenta is a contributing factor in the pathogenesis of PE.

Topics: Animals; Annexin A5; Anticoagulants; Antithrombin III; Blood Pressure; Female; Fetal Death; Fetal Weight; Fibrin; Hemorrhage; Heparin; Hirudin Therapy; Hirudins; Intestines; Liposomes; Male; Mice; Mice, Inbred ICR; Organ Size; Phosphatidylcholines; Phosphatidylserines; Placenta; Platelet Count; Pre-Eclampsia; Pregnancy; Proteinuria

The complement system plays an important role in normal human pregnancy. Uncontrolled activation of this system has been associated with many disease states. We tested the hypothesis that the C5b-9 membrane attack complex (MAC) localizes to sites of villous injury and modulates trophoblast function. Placental sections from pregnancies with no complications, intrauterine growth restriction, or preeclampsia were immunostained and the surface density for MAC and fibrin was determined by morphometric analysis. Primary cytotrophoblasts from term placentas were cultured in a FiO(2) of <1%, 8% and 20% with 10% human serum containing active MAC or heat-inactivated control serum. Immunofluorescent MAC binding to trophoblast was quantified, and the neoepitopes formed in cytokeratin 18 filaments and poly-ADP-ribose polymerase during apoptosis were used to measure cell death. Trophoblast differentiation was assessed by HCG secretion, formation of syncytia, and expression of syncytin. MAC localized to fibrin deposits in normal placentas, and especially in placentas from IUGR and preeclampsia. MAC binding to cytotrophoblasts was inversely proportional to FiO(2) and enhanced apoptosis. MAC increased markers of differentiation in cultures at 72h (medium HCG, syncytia and syncytin expression). Our findings demonstrate that MAC associates with fibrin deposits at sites of villous injury in vivo. Hypoxia also enhances MAC deposition in cultured trophoblasts and MAC alters trophoblast function in a phenotype specific manner.

Topics: Apoptosis; Chorionic Villi; Complement Membrane Attack Complex; Female; Fetal Growth Retardation; Fibrin; Humans; Placenta Diseases; Pre-Eclampsia; Pregnancy; Trophoblasts

We used rats transgenic for the human angiotensinogen (hAogen) gene and the human renin (hRen) gene and crossed the strains to produce a model of preeclampsia in the dams. The female (n=9) hAogen x male hRen cross had severe (telemetry-measured) hypertension and albuminuria, which developed during the last trimester of pregnancy and subsided after delivery. The converse cross (n=9) and control (n=9) SD rats did not. We demonstrated that the female hAogen x male hRen cross had agonistic antibodies capable of activating the angiotensin (Ang) II AT1 receptor (AT1R-AA) and defined the epitope on the receptor's second extracellular loop. The phenomenon also occurs in humans with preeclampsia. The rats displayed renal histology reminiscent of preeclampsia, including fibrin deposition confined to the glomeruli. The complement system was activated in glomeruli and IgG deposits were present that may represent AT1R-AA. Finally, we observed an atherosis-like lesion in the spiral arteries of the placental bed, which we called placental-bed arteriolosclerosis. Our model may be relevant to preeclampsia in humans.

Topics: Angiotensinogen; Animals; Animals, Genetically Modified; Autoantibodies; Complement Activation; Female; Fibrin; Humans; Immunoglobulin G; Kidney Glomerulus; Male; Pre-Eclampsia; Pregnancy; Rats; Rats, Sprague-Dawley; Receptor, Angiotensin, Type 1; Renin

The presence of pro-coagulant and anti-coagulant components of the placental vascular endothelium and syncytiotrophoblast are essential for homeostasis. Vascular endothelium prevents blood clot formation in vivo by involving a cell surface thrombin-binding glycoprotein, thrombomodulin (TM), that activates plasma anti-coagulant protein C. The TM levels increase during pregnancy, but the fibrinolytic capacity diminishes. Since vascular lesions with placental coagulation disorders can be associated with preeclampsia (PE), we hypothesized that TM expression in the stem villous vasculature and syncytiotrophoblast of the placenta are impaired in PE. Plasma and placental tissue samples were collected from PE (n=12) and normotensive pregnant patients (n=11). Patient's gestational age was 35.7+/-1.2 (normotensive) and 30.6+/-1.5 weeks (PE). Blood samples were drawn 30 min before delivery. Serum PAI-1 and PAI-2 antigens were determined by enzyme-linked immunoabsorbent assay (ELISA). A monoclonal antibody specific for TM was used for immunohistochemical tissue staining (ABC) and the staining was quantified by semi quantitative scores. Results show no intensity differences at the apical syncytiotrophoblast between the two groups. However, in preeclamptic placenta, TM expression diminished in the endothelium of the stem villi arteries and increased in the perivascular and stromal myofibroblats in cases of severe PE. TM changes were associated with an increased PAI-1/PAI-2 ratio. It is suggested that in severe PE, the decreased placental blood flow may be due to structural and functional impairment of the endothelium of the stem villi vessels and the surrounding perivascular and stromal myofibroblast, by increasing TM expression which may modulate fetal blow flow in the villous tree.

Topics: Actins; Adult; Biomarkers; Female; Fibrin; Fibroblasts; Humans; Immunohistochemistry; Muscle, Smooth, Vascular; Plasminogen Activator Inhibitor 1; Plasminogen Activator Inhibitor 2; Pre-Eclampsia; Pregnancy; Pregnancy Outcome; Pregnancy Proteins; Severity of Illness Index; Thrombomodulin

The incidence of placental thrombotic lesions in early onset preeclampsia (PE) and/or intrauterine growth restriction (IUGR) were compared between women with and without thrombophilia or hyperhomocysteinemia.. Matched case-control study. 183 women with a history of early onset PE and/or IUGR were tested for thrombophilia and hyperhomocysteinemia. From the 66 women with a thrombophilic factor the placental histological slides were available in 47 women. These were matched for maternal condition (PE and/or IUGR), gestational age at delivery, parity and maternal age, to 47 women with no thrombophilic factor. All slides were revised for lymphohistiocytic villitis, fetal thrombosis and fibrin depositions.. There were no significant differences between the placentas of the matched groups with and without a thrombophilic factor.. Placental thrombotic and inflammatory lesions associated with early onset PE and/or IUGR do not occur more often in women with compared to women without thrombophilia or hyperhomocysteinemia.

Topics: Case-Control Studies; Female; Fetal Growth Retardation; Fibrin; Humans; Hyperhomocysteinemia; Inflammation; Placenta; Pre-Eclampsia; Pregnancy; Thrombophilia; Thrombosis

Morphofunctional study of umbilical cords from pregnancies complicated by preeclampsia shows both activation and lesion of endothelium. The cellular findings in umbilical cords from pregnancies complicated by preeclampsia can be summarized as: (i) higher number of cells with secretion bladders and increase in the number and size of both secretion bladders and microvilli-like protrusions; (ii) increase in collagen, fibrin, fibronectin and lipidic vesicles in the vessel wall; (iii) vacuolization of endothelial cells; (iv) presence of lipidic vacuoles and lipophages in the vessel wall; (v) erosion and disorganisation of the endothelium that exposes extracellular proteins to the blood flow. Endothelial cell cultures from preeclamptic pregnancies show kinetic disorders and cell detachment. The results confirm that an endothelial cell lesion occurs in preeclampsia and this cellular disorder can be reproduced in vitro.

Topics: Adult; Cell Adhesion; Cells, Cultured; Collagen; Endothelium, Vascular; Extracellular Matrix; Female; Fibrin; Fibronectins; Humans; Lipids; Microvilli; Pre-Eclampsia; Pregnancy; Umbilical Cord; Vacuoles

Disseminated intravascular coagulation (DIC) is a frequently observed complication in pregnant women. The laboratory diagnosis of DIC is difficult but the development in the detection of circulating soluble fibrin has improved the possibility.. A number of pregnant women (n= 175) with obstetric complications e.g. preeclampsia, hypertension, intrauterine growth retardation (IUGR) and intrahepatic cholestasis was examined for plasma soluble fibrin and subjected to some routine hemostatic tests, mainly during the third trimester of pregnancy.. Of these patients, 57 of 175 (33%) had an elevated concentration of soluble fibrin (above 23 nmol/L) as compared with a healthy group of women sampled in the third trimester. Eighteen patients (10%) had highly increased levels, above 100 nmol/L. In comparison, none of the 23 healthy, pregnant women investigated had a value above 40 nmol/L.. Hemostatic abnormalities, including increased concentrations of soluble fibrin, are quite frequently observed in women with obstetric complications, most likely as a sign of a systemic activation of coagulation. Although a higher concentration of plasma soluble fibrin was observed in many of the women, no clear correlation to the outcome of the pregnancy was obtained. Whether or not plasma soluble fibrin is of any value, either diagnostically or the treatment of patients with pregnancy complications, remains to be shown.

Topics: Blood Coagulation Tests; Cholestasis, Intrahepatic; Female; Fibrin; Humans; Pre-Eclampsia; Pregnancy; Pregnancy Complications; Pregnancy Complications, Cardiovascular; Reference Values

Our purpose was to determine the hemostatic changes in the uteroplacental and peripheral circulations in normotensive and pre-eclamptic pregnancies.. This prospective, observational study involved 2 patient groups. Group 1 consisted of 30 normotensive women and 22 women with pre-eclampsia who were followed up longitudinally through pregnancy and post partum. Group 2 consisted of 20 women with established pre-eclampsia and 19 normotensive control subjects, all undergoing cesarean section. Plasma levels of thrombin-antithrombin III complex, soluble fibrin, plasmin-alpha2-antiplasmin complex, and fibrin-degradation product (D-dimer) were measured in blood drawn from the antecubital vein (group 1) and from both the antecubital and uterine veins (group 2). Data were analyzed by analysis of variance.. In group 1 levels of thrombin-antithrombin III complex, soluble fibrin, and fibrin-degradation product were significantly higher during normal pregnancy than at 6 weeks post partum. Plasmin-alpha2-antiplasmin complex levels did not change. No differences between the pre-eclamptic and normotensive pregnancy groups were found for any of the hemostatic markers. In group 2 normotensive women undergoing cesarean section, thrombin-antithrombin III complex and soluble fibrin levels were significantly higher in the uterine vein than in the antecubital vein. In group 2 women with pre-eclampsia, thrombin-antithrombin III complex and fibrin-degradation product levels were significantly higher in the uterine vein than in the antecubital vein. In addition, plasmin-alpha2-antiplasmin complex and fibrin-degradation product levels were higher and soluble fibrin levels were lower in the uterine vein in the pre-eclamptic group than in the normotensive group.. Both the coagulation and fibrinolytic systems are activated during normal pregnancy. Activation of these systems is more marked in the uteroplacental circulation than in the systemic circulation in both normotensive and pre-eclamptic pregnancies. An abnormal pattern of hemostasis occurs in the uteroplacental circulation in pre-eclampsia.

Topics: Adult; alpha-2-Antiplasmin; Female; Fibrin; Fibrinolysin; Hemostasis; Humans; Longitudinal Studies; Placenta; Pre-Eclampsia; Pregnancy; Prospective Studies; Uterus

To determine whether decreases in plasma antithrombin (AT) level, as seen in non-gestational acquired AT deficiency, result from a hypercoagulable state and/or liver/kidney damage, AT activity was measured in 24 uncomplicated and 30 preeclamptic women. The fifth percentile of AT levels in the normal pregnancies was used as a cut-off value to subdivide the preeclamptic patients into two groups. Markers of activated coagulation, i.e, levels of thrombin-antithrombin complex (TAT), fibrin D-dimer, soluble fibrin, von Willebrand factor (vWF) and platelet counts, were determined. Indicators of hepatic or renal function, i.e. concentrations of alanine aminotransferase (ALT), aspartate aminotransferase (AST), creatinine, urinary albumin (U-albumin) and serum albumin (S-albumin), were assayed. AT levels were lower in those with preeclampsia than in the normal pregnancy group (P < 0.01). In the group with AT levels less than the cut-off point, levels of fibrin D-dimer (P < 0.05), soluble fibrin (P < 0.05), vWF (P < 0.05), ALT (P < 0.05), AST (P < 0.05), creatinine (P < 0.01) and U-albumin (P < 0.01) were increased, whereas platelet counts (P < 0.05) and S-albumin (P < 0.05) were decreased. All patients with ALT levels > 0.46 mu kat/1, AST > 0.58 mu kat/1, S-albumin < 23 g/1 and/or U-albumin > 4.9 g/24 h had AT levels < or = cut off. AT levels correlated with vWF (rs = - 0.73, P < 0.01) and creatinine (Rs = -0.70, P < 0.01). It is suggested that in preeclampsia, acquired AT deficiency is secondary to a hypercoagulable state, and/or associated with impaired hepatic and/or renal function.

Topics: Alanine Transaminase; Albuminuria; Antithrombin III; Antithrombin III Deficiency; Aspartate Aminotransferases; Creatinine; Female; Fibrin; Humans; Kidney; Liver; Peptide Hydrolases; Pre-Eclampsia; Pregnancy; Pregnancy Complications, Hematologic; Serum Albumin; von Willebrand Factor

Preeclampsia is characterized by maternal hypercoagulable state and intravascular coagulation, microthromboses in several organs, and impairment of uteroplacental circulation. Excessive fibrin deposition occurs in the placenta, suggesting that disorders of placental coagulation and fibrinolysis physiologic systems may have a role in hemostasis activation. Term placentas were collected from 17 hypertensive/preeclamptic women and from 17 healthy pregnant women, and processed for both histologic and hemostasis studies. Placental fibrinoid deposition was visualized by cresyl-violet staining and quantified by histomorphometric analysis. The content in hemostasis factors was measured on extracts from homogenized placentas treated by a nonionic detergent. The percentage of villi with fibrinoid deposits was higher in the diseased placentas than in controls: 13.2 +/- 11.2 versus 6.75 +/- 2.7% (p < 0.001) for the total amount of deposits; 4.8 +/- 6.7 versus 1.5 +/- 1.0% (p = 0.04) for perivillous fibrinoid deposits, which are considered as histologic markers of intraplacental fibrin. The content in type 2 plasminogen activator inhibitor (PAI-2) antigen was higher in the diseased placentas than in controls: 124 +/- 8 versus 104 +/- 6 ng/mg placental protein (p = 0.046); there was a negative correlation between PAI-2 antigen and thrombomodulin activity (r = -0.57, p = 0.02) in the diseased placentas. No significant differences were found between the two groups for placental procoagulant tissue factor and anticoagulant thrombomodulin activities, and for the content in plasminogen activators and PAI-1 antigens. Placental antifibrinolytic potential is increased in pregnancy-induced hypertension and preeclampsia. This change, and the association of the highest PAI-2 placental concentrations with the lowest concentrations of thrombomodulin, may contribute to the prethrombotic state and to the excessive placental perivillous fibrin deposition observed in these situations.

Topics: Adult; Female; Fibrin; Fibrinolysis; Hemostasis; Humans; Hypertension; Placenta; Plasminogen Activator Inhibitor 1; Pre-Eclampsia; Pregnancy; Pregnancy Complications, Cardiovascular; Thrombomodulin

We tested the hypothesis that enhanced intravascular coagulation in pregnancy could produce clinical symptoms similar to those of preeclampsia, such as hypertension, proteinuria, and edema. Having confirmed this, we then examined whether the pathological changes caused by intravascular coagulation could be suppressed by administration of antithrombin III (AT III), an endogenous inhibitor active to thrombin and factor X a. Intravascular coagulation was induced in Wistar rats on day 16-20 of pregnancy by 1-h arterial infusion of tissue thromboplastin (TP) through the left ventricle of the heart. One hour after the end of the infusion period, organ blood flows were measured by the radioactive ((57)Co-labeled) microsphere method, and fibrin deposition in organs was measured by radiolabeling with [(125)I] fibrinogen injected before TP infusion. Infusion of TP produced fibrin deposition in the kidney, lung, and liver, but not in the myometrium and placenta, as well as an 80% decrease in renal blood flow (RBF), with oliguria and proteinuria. TP also caused an increase in blood pressure (BP) accompanied by an increase in plasma renin activity (PRA), both of which were suppressed by bilateral nephrectomy before TP infusion. The prophylactic administration of AT III concentrates (60 or 300 U/kg intravenously (i.v.), followed by infusion of 30 or 150 U/kg/2 h, respectively) prevented all pathological changes in a dose-dependent manner. AT III increased placental blood flow regardless of the state of coagulation. These findings suggest that intravascular coagulation plays a significant part in the pathophysiology of preeclampsia and that AT III concentrates may have therapeutic potential in the treatment of this condition.

Topics: Animals; Antithrombin III; Blood Coagulation; Female; Fibrin; Hypertension; Kidney; Pre-Eclampsia; Pregnancy; Pregnancy Complications, Cardiovascular; Proteinuria; Rats; Rats, Wistar; Regional Blood Flow; Renin; Serum Albumin; Thromboplastin

Biopsy specimens were obtained under direct vision at the time of cesarean section from 42 patients (33 preeclamptic and nine normotensive patients) and from three hysterectomies (all in normotensive patients). Mean gestational age was 32.8 +/- 0.9 week (range, 26 to 40 weeks) in women with preeclampsia and 36.1 +/- 1.1 weeks in normotensive women (range, 32 to 41 weeks). Tissues were obtained from the central placental bed and from nonplacental sites. Specimens were examined histologically and by electron microscopy. Ultrastructural changes in small vessels, primarily venules, were compared with preeclamptic blood pressure. Extensive ultrastructural endothelial injury was found consistently in both site and nonsite areas in all of the specimens from women with preeclampsia but not in normotensive women (p less than 0.0001). There was no apparent correlation between the type or degree of endothelial damage and maternal hypertension. The same types and relative severity of specific vascular injury were present in both placental and nonplacental sites. Endothelial and derivative vascular injury occurs more or less uniformly in the uterus in preeclampsia, especially along the boundary zone between maternal and fetal tissues.

Topics: Animals; Arterioles; Cytoplasm; Endothelium, Vascular; Female; Fibrin; Microcirculation; Placenta; Pre-Eclampsia; Pregnancy; Rats; Uterus; Venules

This study reviews liver disease in toxemia of pregnancy based on 102 cases submitted to the Armed Forces Institute of Pathology. The common clinical features were right upper quadrant and epigastric pain, nausea, vomiting, and elevation of the serum transaminases. Jaundice occasionally developed. These occurred in severe preeclampsia or eclampsia and their cause was usually recognized. However, hepatic symptoms and signs did result in inappropriate diagnoses and misdirected therapy. Such confusion occurred when these were the initial problems confronting the clinician in women presenting with advanced toxemia due to poor prenatal care. They were also likely to be misleading when other more classic parameters, such as blood pressure and proteinuria, were only midly abnormal. Central nervous system complications were the common cause of death but liver disease could be partially or wholly responsible. Extensive periportal lesions, hepatic hematomas, spontaneous rupture, and infarction all contributed to hepatic injury and to morbidity. Fibrin deposition, hemorrhage, or both in the periportal areas was characteristic of the histopathology. Scanning electron microscopy validated this spectrum of change. A toxemic vasculopathy related to severe vasospasm in the hepatic arterial circulation may be responsible.

Topics: Eclampsia; Female; Fibrin; Hemorrhage; Humans; Infarction; Liver; Liver Diseases; Necrosis; Pre-Eclampsia; Pregnancy

Fibrin-fibrinogen degradation products and SP 1 were measured in about 150 women with normal pregnancies. The mean levels of both parameters rose up to term. In 13 normal pregnancies the SP 1 course never decreased. Elevated levels of SP 1 were measured in 4 out of 10 cases of mild gestosis. In 11 cases of severe gestosis, however, 7 had increased values. A decrease of elevated levels correlated to a clinical deterioration. SP 1 was normal in the most cases of severe gestosis, but a fall of SP 1 indicated an impaired placental function resulting in small-for-date baby or imminent foetal asphyxia. The measurements of fibrinogen degradation products and of the course of SP 1 are helpful in the diagnosis of gestosis.

Topics: Female; Fetal Death; Fetal Growth Retardation; Fibrin; Fibrin Fibrinogen Degradation Products; Gestational Age; Humans; Pre-Eclampsia; Pregnancy; Pregnancy Proteins; Pregnancy-Specific beta 1-Glycoproteins; Risk

Normal, rigid and fibrotic utero-placental arteries are resistant to the action of circulating vaso-motor substances. In contrast, the persistence and the hyperplasia of smooth muscle fibres result in a reduced flow in the intervillous compartment and a sensitivity of the vessels to vaso-constrictor substances. These lesions, which develop after the twentieth week, provide the necessary conditions for the subsequent development of the characteristic vicious cycles of eclampsia.

Topics: Arteries; Complement C3; Female; Fibrin; Fluorescent Antibody Technique; Humans; Hyperplasia; Immunoglobulin A; Immunoglobulin G; Immunoglobulin M; Maternal-Fetal Exchange; Placenta; Pre-Eclampsia; Pregnancy; Uterus

Topics: Capillaries; Female; Fibrin; Humans; Microscopy, Electron; Placenta; Pre-Eclampsia; Pregnancy; Trophoblasts

Placental bed biopsies were performed during caesarean section in a series of 137 patients. Analysis of the morphological findings confirms that vascular physiological changes were reduced in pre-eclampsia and in normotensive intrauterine growth retardation. In pre-eclampsia, acute atherosis in the decidual segments of uteroplacental arteries was a prominent feature. Intimal thickenings of the myometrial segments of the uteromaternal arteries were also noted. Normotensive intrauterine growth retardation cases were characterized by intimal thickenings of the myometrial segments of the uteroplacental arteries. Immunofluorescent investigations have demonstrated that the deep vascular stenoses were not associated with immunoglobulin deposition while in distal arterial segments displaying acute atherosis a positive immunofluorescence for IgG and fibrin and, more irregularly, for C'3 and IgM could be noted. These findings lead us to suggest that an immunological mechanism may be involved in the pathogenesis of acute atherosis.

Topics: Complement C3; Female; Fetal Growth Retardation; Fibrin; Fluorescent Antibody Technique; Humans; Immunoglobulin G; Ischemia; Placenta; Placenta Diseases; Placental Insufficiency; Pre-Eclampsia; Pregnancy

Topics: Arteries; Female; Fetal Growth Retardation; Fibrin; Humans; Immunoglobulins; Placenta; Pre-Eclampsia; Pregnancy; Uterus

The glomerular lesions of preeclampsia consist of swelling of endothelial cells, interposition of mesangial cells and matrix between the endothelial cells and the glomerular basement membrane, and organization of subendothelial deposits of incompletely characterized material. Fibrin and immunoglobulins have previously been localized to these deposits. Laminin, a large basement membrane glycoprotein, type IV collagen, fibronectin, and a basement membrane proteoglycan were found in moderate amounts in the mesangium and prominently in the thickened glomerular capillary walls of patients with preeclampsia or other hypertensive syndromes of pregnancy. Fibrin showed the same pattern of distribution as that of fibronectin. The material deposited in the subendothelial layer of the capillary loops thus consists not only of plasma-derived proteins but also structural components of the glomerular basement membrane and of the mesangial matrix. Type I collagen deposits were demonstrated only in mesangium of pregnant patients with chronic or recurrent hypertension. Glomerular epithelial and mesangial cells synthesize in vitro the basement membrane proteins that accumulate in glomeruli of pregnant hypertensive patients. We have tested the influence of some of the pathophysiologic changes occurring during preeclampsia on the biosynthesis of collagen by rat glomerular epithelial and mesangial cells. Addition of indomethacin to the cultures transiently inhibited the synthesis of prostaglandins (PGE2) and of collagen. Addition of exogenous fibronectin to the media stimulated the production of collagen by mesangial and epithelial cells. Alterations in the metabolism of prostaglandins and the increased deposition of fibronectin observed during preeclampsia could thus play a pathogenic role in the accumulation of basement membrane proteins in glomeruli of these patients.

Topics: Basement Membrane; Collagen; Female; Fibrin; Fibronectins; Glycoproteins; Humans; Hypertension; Indomethacin; Kidney Glomerulus; Laminin; Membrane Proteins; Pre-Eclampsia; Pregnancy; Pregnancy Complications, Cardiovascular; Prostaglandins

Topics: Blood Viscosity; Female; Fetal Growth Retardation; Fibrin; Fibrin Fibrinogen Degradation Products; Hemostasis; Humans; Platelet Count; Pre-Eclampsia; Pregnancy; Pregnancy Trimester, Third

Histopathologic lesions of toxemia of pregnancy found in 46 first trimester-induced abortions and 82 women with kidney biopsies are reviewed and discussed. Decidual arteriolar vasospasm and degeneration, syncytial trophoblastic degeneration, and chorionic villous fibrin deposits characterize the early toxemic changes of the uterus and placenta. Pure toxemic glomerular, arteriolar, tubular, and juxtaglomerular alterations were present in about 40% of the kidney biopsies. Others had arteriolar nephrosclerosis, chronic glomerulonephritis or both. Two women had renovascular hypertension. Excessive vascular permeability predisposed to fibrinogen leakage and fibrin deposits. The mechanisms of preclinical toxemia of pregnancy and clinical preeclampsia are considered in view of these biopsy observations.

Topics: Female; Fibrin; Humans; Kidney; Placenta; Pre-Eclampsia; Pregnancy; Uterus

Topics: Arteries; Blood Coagulation; Blood Platelets; Factor VIII; Female; Fibrin; Fibrinogen; Humans; Placenta; Plasminogen Activators; Pre-Eclampsia; Pregnancy

Topics: Female; Fibrin; Fibrinogen; Humans; Hypertension; Pre-Eclampsia; Pregnancy; Pregnancy Complications, Cardiovascular; Proteinuria; Reference Values; Streptokinase

Topics: Basement Membrane; Capillaries; Eclampsia; Endothelium; Epithelium; Female; Fibrin; Foam Cells; Humans; Kidney; Kidney Diseases; Kidney Glomerulus; Lipids; Pre-Eclampsia; Pregnancy; Pregnancy Complications; Thrombosis

Topics: Abortion, Threatened; alpha-Fetoproteins; Eclampsia; Female; Fetal Death; Fibrin; Fibrinogen; Glycoproteins; Humans; Pre-Eclampsia; Pregnancy; Pregnancy Complications; Pregnancy, Multiple

Topics: Adult; Disseminated Intravascular Coagulation; Female; Fibrin; Fibrin Fibrinogen Degradation Products; Fibrinogen; Humans; Kidney Diseases; Methods; Pre-Eclampsia; Pregnancy

Topics: Blood Coagulation; Disseminated Intravascular Coagulation; Eclampsia; Female; Fibrin; Fibrinogen; Humans; Kidney; Pre-Eclampsia; Pregnancy

Topics: Adult; Female; Fibrin; Fibrinogen; Hemostasis; Humans; Platelet Adhesiveness; Platelet Aggregation; Pre-Eclampsia; Pregnancy; Pregnancy Trimester, Second; Pregnancy Trimester, Third; Thrombelastography

Topics: Female; Fibrin; Humans; Pre-Eclampsia; Pregnancy

Topics: Female; Fibrin; Fibrinogen; Humans; Pre-Eclampsia; Pregnancy; Protein Conformation; Solubility

Topics: Chorion; Female; Fibrin; Fibrinolysis; Gestational Age; Humans; Pre-Eclampsia; Pregnancy

Significantly increased concentrations of soluble fibrinogen/fibrin complexes were found in plasma samples from ten normal pregnant women when compared with ten non-pregnant age-matched controls. In ten women with pre-eclampsia mean soluble complex concentration was more than three times that in the age, parity, and gestation matched pregnant controls. Soluble fibrinogen/fibrin complexes are also found in the plasma of patients in various hypercoagulable and thrombotic states, including disseminated intravascular coagulation. These findings provide additional evidence that pre-eclampsia is associated with disseminated intravascular coagulation.

Topics: Antigens; Disseminated Intravascular Coagulation; Female; Fibrin; Fibrinogen; Humans; Immune Complex Diseases; Pre-Eclampsia; Pregnancy; Pregnancy Complications, Hematologic; Solubility

Topics: alpha-Macroglobulins; Complement C3; Complement C4; Eclampsia; Female; Fibrin; Humans; Immunoglobulin A; Immunoglobulin E; Immunoglobulin G; Immunoglobulin M; Kidney; Kidney Glomerulus; Pre-Eclampsia; Pregnancy

Renal biopsies in 14 patients with P.E.T. or eclampsia showed constant I.F. reactions for IgM and fibrin, with frequent reactions for C1q and C3. The glomeruli showed reversible mesangial proliferation and swelling, with characterictic E.M. deposits, and segmental lesions were present in seven patients. Similar I.F. reactions occurred in three other patients with clinical diagnoses of P.E.T. whose biopsies demonstrated coexistent glomerular disease. Serum complement studies showed a significant rise in C3 in the third trimester of normal pregnancies and a further significant elevation in C1q and C3 in the third trimester of a series of unselected P.E.T. patients. In contrast, four patients from the biopsy series with eclampsia or severe P.E.T. showed profound depression of serum C3 and C4, at the time of maximum clinical severity, which was shown to return to normal in two patients. The I.F. findings confirm those of Petrucco et al (6), and, with the other data, suggest that immune-complex deposition and activation of the classical complement pathway could interrect with intravascular coagulation to produce the glomerular lesions of P.E.T. and eclampsia.

Topics: Adolescent; Adult; alpha-Macroglobulins; Complement C1; Complement C3; Complement C4; Complement System Proteins; Eclampsia; Female; Fibrin; Humans; Immunoglobulin M; Kidney; Kidney Glomerulus; Postpartum Period; Pre-Eclampsia; Pregnancy

Components of the haemostatic mechanism were studied at intervals in 60 primigravidae over the course of pregnancy and the puerperium; 12 of these developed pre-eclampsia. During pregnancy there was a fall in fibrinolytic activity and fibrinolytic capacity and a rise in fibrinogen, FR-antigen, alpha 1-antitrypsin and alpha 2-macroglobulin. The women who subsequently developed pre-eclampsia could not be identified on the basis of these measurements. Following delivery there was a more rapid return of fibrinolytic activity and capacity towards normal in the women who had not had pre-eclampsia. The urinary FR-antigen level was higher in the women with pre-eclampsia.

Topics: Adolescent; Adult; alpha 1-Antitrypsin; alpha-Macroglobulins; Antigens; Female; Fibrin; Fibrinogen; Fibrinolysis; Humans; Plasminogen; Pre-Eclampsia; Pregnancy

To investigate if fibrin (or fibrinogen), immunoglobulins and complement were present in the liver of patients with toxemia of pregnancy, we performed immunofluorescence studies on needle biopsies of pre-eclamptic women. Fibrin (or fibrinogen) outlining the hepatic sinusoids was found in all 12 cases; in two of them there were also large nodular deposits of fibrin (or fibrinogen) and to a lesser extent of IgG, IgM and C3 in areas of necrosis. Immunofluorescence study of 13 control liver biopsies, six from pregnant women, was negative. Our findings suggest that the factors involved in glomerular and hepatic injury are similar. To explain the predominant involvement of liver and kidney, we propose that in these organs, the vasospasm characteristic of toxemia is more severe; this enhanced severity, in the presence of a systemic yet mild blood hypercoagulability, would create adequate local conditions for the precipitation of fibrin-fibrinogen.

Topics: Adolescent; Adult; Complement C3; Female; Fibrin; Fibrinogen; Humans; Immunoglobulin G; Immunoglobulin M; Immunoglobulins; L-Lactate Dehydrogenase; Liver; Pre-Eclampsia; Pregnancy

Topics: Blood Coagulation; Disseminated Intravascular Coagulation; Eclampsia; Female; Fibrin; Fibrinolysis; Histocytochemistry; Humans; Labor, Obstetric; Pre-Eclampsia; Pregnancy

On healthy individuals fibrin(ogen) split products cannot be demonstrated in the blood. Catabolic products of fibrin and fibrinogen appear in the blood in case of general fibrinolysis, consumption coagulopathy with secondary fibrinolysis as well as local fibrin films with secondary fibrinolysis. The regular routine determination of fibrin(ogen) split products in serum or urine may indicate starting complications of many diseases. The appearance of these split products in case of renal affections indicates acute and active processes on the kidneys themselves; fibrin films appear in case of acute and chronic glomerulonephritis, casting-off crises on renal transplants, EPH gestosis, renal phlebothrombosis, hemolytic-uremic syndrom and occasionally urinary tract infections. The demonstration of fibrin(ogen) split products in serum or urine allows the following conclusions: a) acute and active process on the kidneys themselves; b) HMWS in urine indicate a fibrin film in the kidneys; c) an immediate beginning of an anticoagulation therapy; d) good possibilities to judge the therapeutic effect and by this the further progress of disease.

Topics: Disseminated Intravascular Coagulation; Female; Fibrin; Fibrinogen; Fibrinolysis; Glomerulonephritis; Graft vs Host Reaction; Hemolytic-Uremic Syndrome; Humans; Immunoelectrophoresis; Infant; Kidney Diseases; Kidney Transplantation; Molecular Weight; Pre-Eclampsia; Pregnancy; Prognosis; Thrombosis; Transplantation, Homologous; Urinary Tract Infections

Topics: Antithrombins; Blood Coagulation; Blood Coagulation Factors; Cesarean Section; Estradiol; Female; Fibrin; Fibrinogen; Fibrinolysis; Humans; Immunodiffusion; Placenta; Pre-Eclampsia; Pregnancy; Pregnancy Trimester, Third; Progesterone; Prothrombin Time; Regional Blood Flow; Uterus

Topics: Anemia, Hemolytic; Disseminated Intravascular Coagulation; Eclampsia; Endothelium; Female; Fibrin; Fibrinogen; Fluorescent Antibody Technique; Humans; Kidney Glomerulus; Pre-Eclampsia; Pregnancy; Pregnancy Complications, Hematologic

Topics: Animals; Blood Cell Count; Blood Platelets; Blood Pressure; Decidua; Dietary Proteins; Eclampsia; Female; Fibrin; Pre-Eclampsia; Pregnancy; Rabbits; Serum Albumin; Sodium Chloride; Tissue Extracts

Topics: Adult; Arteries; Biopsy; Child; Disseminated Intravascular Coagulation; Female; Fibrin; Graft Rejection; Humans; Hypertension, Malignant; Kidney; Kidney Diseases; Kidney Glomerulus; Kidney Tubular Necrosis, Acute; Pre-Eclampsia; Pregnancy; Scleroderma, Systemic; Transplantation, Homologous; Vascular Diseases

A prospective evaluation of the haemostatic mechanism was undertaken in 15 normal primigravidas and in 12 primigravidas with mild to moderately severe pre-eclampsia in order to further examine the possibility that disseminated intravascular coagulation may occur in this clinical syndrome. The only coagulation abnormality demonstrated was a prolongation of bleeding time. The data do not support the suggestion that significant disseminated intravascular coagulation is associated with pre-eclampsia. The addition of the heparinoid drug sodium pentosan polysulphate to the therapeutic regimen resulted in a significant fall in platelet factor 3 availability and in decreased aggregation against ADP but conferred no objective clinical improvement. We conclude that the drug has no place in the management of established pre-eclampsia.

Topics: Adenosine Diphosphate; Adult; Blood Coagulation Tests; Disseminated Intravascular Coagulation; Female; Fibrin; Fibrinogen; Humans; Pentosan Sulfuric Polyester; Platelet Aggregation; Platelet Factor 3; Pre-Eclampsia; Pregnancy; Pregnancy Complications, Hematologic; Prospective Studies

In view of the association between pre-eclampsia and disseminated intravascular coagulation, three patients presenting with severe pre-eclampsia before the 28th week of pregnancy were treated with heparin. In all three patients, there was deterioration of hypertension and proteinuria that necessitated the withdrawal of treatment after five to six days. During treatment, serum and urinary fibrinolytic degradation products (FDPs) continued to rise or remained unaltered, plasminogen levels showed a steady fall, and the platelet count remained at a reduced level. These data suggest that heparin was an ineffective form of treatment and did not prevent the intravascular fibrin deposition associated with severe pre-eclampsia.

Topics: Blood Cell Count; Blood Coagulation Tests; Blood Platelets; Dipyridamole; Disseminated Intravascular Coagulation; Female; Fibrin; Heparin; Humans; Hypertension; Pre-Eclampsia; Pregnancy; Pregnancy Trimester, Second; Proteinuria

Topics: Disseminated Intravascular Coagulation; Female; Fibrin; Fibrin Fibrinogen Degradation Products; Humans; Pre-Eclampsia; Pregnancy

Topics: Abortion, Habitual; Abortion, Threatened; Animals; Basement Membrane; Colloids; Female; Fetal Death; Fetal Diseases; Fibrin; Glycosaminoglycans; Humans; Infant, Newborn; Infant, Premature; Iron; Mice; Necrosis; Placenta; Placenta Diseases; Pre-Eclampsia; Pregnancy; Pregnancy Complications; Staining and Labeling; Trophoblasts

Topics: Adenosine Diphosphate; Adult; Blood Cell Count; Blood Coagulation Tests; Blood Platelets; Disseminated Intravascular Coagulation; Female; Fibrin; Fibrinogen; Humans; Labor, Obstetric; Microscopy, Phase-Contrast; Platelet Adhesiveness; Postpartum Period; Pre-Eclampsia; Pregnancy; Protamines; Prothrombin Time; Thrombocytopenia; Time Factors

Topics: Female; Fibrin; Fluorescent Antibody Technique; Gestational Age; Histocytochemistry; Humans; Immunoglobulin G; Infant, Newborn; Maternal-Fetal Exchange; Placenta; Placenta Diseases; Pre-Eclampsia; Pregnancy; Tetanus Antitoxin

Topics: Diabetes Mellitus; Evaluation Studies as Topic; Female; Fibrin; Fibrinogen; Glycosuria; Humans; Immunoelectrophoresis; Latex Fixation Tests; Liver Diseases; Methods; Pre-Eclampsia; Pregnancy; Pregnancy Complications; Urinary Tract Infections

Topics: Animals; Chorionic Gonadotropin; Female; Fibrin; Glycogen; Glycoproteins; Glycosaminoglycans; Humans; Hydatidiform Mole; Kidney; Obstetric Labor Complications; Placenta; Pre-Eclampsia; Pregnancy; Rats; Staining and Labeling

Topics: Aminocaproates; Animals; Blood Pressure; Blood Vessels; Creatinine; Disease Models, Animal; Female; Fibrin; Fibrinolysis; Half-Life; Iodine Isotopes; Kidney; Kidney Glomerulus; Liver; Lung; Placenta; Povidone; Pre-Eclampsia; Pregnancy; Proteinuria; Rabbits; Renin

Topics: ABO Blood-Group System; Abortion, Spontaneous; Adult; Age Factors; Bacteriuria; Blood Coagulation; Blood Coagulation Tests; Blood Group Antigens; Delivery, Obstetric; Disseminated Intravascular Coagulation; Estrogens; Female; Fibrin; Fibrinogen; Fibrinolysis; Humans; Lactation; Parity; Pre-Eclampsia; Pregnancy; Pregnancy Complications; Pregnancy Complications, Infectious; Protamines; Puerperal Disorders; Smoking; Staphylococcus; Time Factors

Topics: Animals; Disease Models, Animal; Disseminated Intravascular Coagulation; Female; Fibrin; Fibrinogen; Humans; Placenta; Pre-Eclampsia; Pregnancy; Rabbits; Thromboplastin

Topics: Acute Disease; Acute Kidney Injury; Adult; Biopsy; Blood Vessels; Capillaries; Female; Fibrin; Follow-Up Studies; Humans; Kidney; Kidney Glomerulus; Microscopy, Electron; Microscopy, Fluorescence; Pre-Eclampsia; Pregnancy; Prognosis; Proteinuria; Puerperal Disorders

Topics: Acute Kidney Injury; Basement Membrane; Blood Coagulation Disorders; Diabetic Nephropathies; Disseminated Intravascular Coagulation; Female; Fibrin; Fibrinogen; Fibrinolysis; Glomerulonephritis; Hemagglutination Tests; Hemolytic-Uremic Syndrome; Humans; Ischemia; Kidney; Kidney Diseases; Male; Middle Aged; Pre-Eclampsia; Pregnancy; Thrombosis; Urokinase-Type Plasminogen Activator

Topics: Albuminuria; Disseminated Intravascular Coagulation; Female; Fibrin; Fibrinogen; Humans; Pre-Eclampsia; Pregnancy

Topics: Disseminated Intravascular Coagulation; Female; Fibrin; Fibrinogen; Humans; Kidney Glomerulus; Pre-Eclampsia; Pregnancy

Topics: Female; Fibrin; Glomerulonephritis; Humans; Pre-Eclampsia; Pregnancy; Proteinuria

Topics: Abortion, Missed; Abruptio Placentae; Blood Coagulation Tests; Collagen Diseases; Erythrocytes; Esters; Female; Fibrin; Fibrinolysis; Fluorides; Hemagglutination Inhibition Tests; Humans; Kidney Diseases; Latex Fixation Tests; Leukemia; Ovarian Neoplasms; Pre-Eclampsia; Pregnancy; Pyruvates; Shock; Staphylococcus; Uterine Neoplasms

Topics: Animals; Blood Coagulation; Female; Fibrin; Fibrinogen; Glomerular Filtration Rate; Metabolic Clearance Rate; Osmolar Concentration; Pre-Eclampsia; Pregnancy; Pregnancy Complications, Cardiovascular; Rabbits; Technetium; Water

Topics: Basement Membrane; Eclampsia; Epithelial Cells; Female; Fibrin; Humans; Kidney Glomerulus; Microscopy, Electron; Pre-Eclampsia; Pregnancy

Topics: Female; Fibrin; Fibrinogen; Humans; Pre-Eclampsia; Pregnancy

Topics: Biopsy; Carbamates; Eclampsia; Female; Fibrin; Gestational Age; Humans; Immunosuppressive Agents; Lymph Nodes; Pre-Eclampsia; Pregnancy; Vascular Diseases

Topics: Blood Cell Count; Blood Sedimentation; C-Reactive Protein; Clinical Enzyme Tests; Female; Fibrin; Humans; Hyaluronoglucosaminidase; Pre-Eclampsia; Pregnancy; Prognosis; Reticulocytes

Topics: Blood Coagulation; Blood Platelets; Eclampsia; Female; Fibrin; Fibrinogen; Fibrinolysin; Fibrinolysis; Humans; Lung; Plasminogen; Pre-Eclampsia; Pregnancy; Radiography; Radionuclide Imaging; Technetium; Thrombocytopenia

The coagulation and fibrinolytic mechanisms were investigated in a group of patients with severe pre-eclampsia and eclampsia and the findings were compared with those of healthy women in late pregnancy. In patients with pre-eclampsia the following significant differences were found: (1) greater depression of plasma fibrinolytic activity (euglobulin lysis time) than in normal pregnancy, (2) a higher level of inhibitor to urokinaseinduced lysis, (3) increased levels of serum fibrin degradation products, and (4) reduced platelet counts.In patients with eclampsia a progressive increase of the level of serum fibrin degradation products was found over the three days following eclamptic seizures. No such increase occurred after grand mal seizures in late pregnancy. The findings in this study support the view that intravascular clotting is taking place in pre-eclampsia and that this disturbance of the balance between coagulation and fibrinolysis may be localized to certain areas of the vascular compartment, particularly the placental and renal circulations. Fibrin deposition in the maternal vessels supplying the placenta would impair the placental blood flow, which may explain the placental insufficiency which occurs in pre-eclampsia. Likewise fibrin deposition in the renal vasculature will result in glomerular damage and proteinuria. Hypertension may be related to the renal ischaemic changes or a compensatory response to the presence of fibrin deposition in the vascular compartment. This evidence of intravascular fibrin deposition raises the question of the possible therapeutic value of antithrombotic agents to inhibit the clotting process. On a theoretical basis such treatment might be expected to improve blood flow to the placenta and thereby fetal growth.

Topics: Adult; Blood Coagulation; Blood Platelets; Eclampsia; Embryonic and Fetal Development; Epilepsy, Tonic-Clonic; Female; Fibrin; Fibrinolysis; Fibrinolytic Agents; Humans; Hypertension; Ischemia; Kidney; Kidney Diseases; Maternal-Fetal Exchange; Placenta; Pre-Eclampsia; Pregnancy; Proteinuria; Serum Globulins

Topics: Biopsy; Erythrocytes; Extraembryonic Membranes; Female; Fibrin; Humans; Microscopy, Electron; Placenta; Postpartum Period; Pre-Eclampsia; Pregnancy; Uterus

Topics: Adult; Arm; Chronic Disease; Female; Fibrin; Fibrinogen; Fibrinolysis; Hemiplegia; Humans; Immobilization; Leg; Macroglobulins; Male; Middle Aged; Plasminogen; Posture; Pre-Eclampsia; Pregnancy; Thrombophlebitis

Topics: Adenosine Diphosphate; Adult; Antithrombins; Blood Cell Count; Blood Coagulation; Blood Coagulation Tests; Blood Platelets; Cold Temperature; Factor V; Factor VIII; Female; Fibrin; Fibrinogen; Fibrinolysis; Fibrinolytic Agents; Humans; Hypertension; Placenta; Placenta Diseases; Plasminogen; Platelet Adhesiveness; Postpartum Period; Pre-Eclampsia; Pregnancy; Pregnancy Complications, Cardiovascular; Thromboplastin

Topics: Albuminuria; Eclampsia; Edema; Female; Fibrin; Humans; Hypertension; Pre-Eclampsia; Pregnancy

Topics: Antibody Formation; Antigen-Antibody Reactions; Blood Group Incompatibility; Erythroblastosis, Fetal; Female; Fibrin; Humans; Kidney Glomerulus; Leukocytes; Maternal-Fetal Exchange; Placenta; Pre-Eclampsia; Pregnancy; Rh-Hr Blood-Group System

Serum levels of fibrinogen/fibrin degradation products, measured in African women, were significantly higher in pre-eclamptic toxaemia than in normal pregnancy, and were significantly higher with eclampsia than with toxaemia. These findings are in accord with the hypothesis that eclampsia and toxaemia are associated with disseminated intravascular coagulation, which may be responsible for certain clinical manifestations of these conditions.

Topics: Blood Coagulation Disorders; Disseminated Intravascular Coagulation; Eclampsia; Female; Fibrin; Fibrinogen; Fibrinolysis; Humans; Postpartum Period; Pre-Eclampsia; Pregnancy

Topics: Animals; Female; Fibrin; Kidney; Placenta; Pre-Eclampsia; Pregnancy; Rabbits; Uterus

Topics: Adult; Antigen-Antibody Reactions; Biopsy; Cardiovascular Diseases; Cesarean Section; Female; Fibrin; Humans; Hypertension; Kidney Diseases; Kidney Glomerulus; Kidney Tubules; Lysosomes; Obstetric Labor Complications; Placenta; Pre-Eclampsia; Pregnancy; Pregnancy Complications, Cardiovascular; Pyelonephritis; Serotonin

Topics: Female; Fibrin; Fibrinogen; Fibrinolysis; Humans; Hypertension, Renal; Pre-Eclampsia; Pregnancy

Topics: Basement Membrane; Female; Fetal Death; Fibrin; Humans; Hypertension; Hypoxia; Photomicrography; Placenta; Pre-Eclampsia; Pregnancy

Topics: Adolescent; Adult; Female; Fetal Death; Fibrin; Humans; Infarction; Placenta; Postpartum Hemorrhage; Pre-Eclampsia; Pregnancy

Topics: Animals; Electrons; Female; Fibrin; Glomerulonephritis; Humans; Kidney Diseases; Kidney Glomerulus; Microscopy; Microscopy, Electron; Pathology; Phagocytosis; Pre-Eclampsia; Pregnancy; Rabbits; Research; Sepsis; Thromboplastin

An immunofluorescent study of renal biopsies from patients with toxemia of pregnancy has been performed. It was found that the glomeruli consistently showed bright staining for fibrin within endothelial cells, as well as occasional deposits along the basement membrane. Gamma globulin was only occasionally demonstrable, generally in the form of irregular deposits along the basement membrane. beta(1C) was absent and albumin was not seen in glomeruli, except sometimes in the form of droplets within epithelial cells. In biopsies from pregnant patients without toxemia only equivocal staining for fibrin was seen. On the basis of these observations and other evidence discussed, it is proposed that the accumulation of fibrin in glomeruli reflects a prolonged state of intravascular clotting in toxemia and that the arrest in glomeruli of some form of circulating fibrin constitutes the basic pathogenic mechanism of the glomerular damage in this disease.

Topics: Basement Membrane; Biopsy; Epithelial Cells; Female; Fibrin; Humans; Kidney Diseases; Kidney Glomerulus; Pathology; Pre-Eclampsia; Pregnancy

Topics: Blood; Blood Pressure; Female; Fibrin; Humans; Hypertension; Pre-Eclampsia; Pregnancy; Serum; Thrombolytic Therapy; Toxemia