fibrin and Placenta-Diseases

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

Chronic intervillositis (CI) is a rare placental condition involving diffuse infiltration of intervillous spaces by CD68- or CD45-positive maternal mononuclear inflammatory cells. Because no validated clinical or biochemical markers are specific to CI, the diagnosis is purely histopathological and is made postpartum.. This report describes a case of recurrent CI associated with adverse complications in two successive pregnancies. Both pregnancies were complicated by intrauterine growth restriction. Coexistent massive perivillous fibrin deposition was present in the first placenta. This case highlights the importance of CI in explaining and predicting adverse perinatal outcomes.. CI is associated with adverse pregnancy outcomes and a high risk of recurrence, and it can coexist with massive perivillous fibrin deposition. Pathologists must ensure that the significance of these diagnoses is adequately conveyed to clinicians, to optimize management of subsequent pregnancies.

Topics: Adult; Chorionic Villi; Chronic Disease; Female; Fetal Growth Retardation; Fibrin; Humans; Placenta Diseases; Pregnancy; Recurrence

Maternal floor infarction/massive perivillous fibrin deposition (MFI/MFD), chronic histiocytic intervillositis (CHIV) and villitis of unknown etiology (VUE) are lesions of the placenta which are characterized morphologically. The cause is thought to be pathological immunotolerance/rejection reaction at the fetomaternal interface. The risk of recurrence is elevated and the lesions can lead to severe pediatric diseases.. This article provides an overview of the pathological and anatomical characteristics of each of these lesions, including diagnostic criteria, suspected etiology, clinical relevance and suggested therapy options.. A selective search of the literature was carried out and experiences from own diagnostic clientele are presented.. While MFI/MFD and CHIV occur more rarely, VUE is relatively common occurring in up to 15 % of placentas at term. Both MFI/MFD and CHIV can occur in the first and second trimester, while VUE typically manifests in the third trimester. All lesions can lead to intrauterine growth retardation or abortion and have a tendency towards disease recurrence. Furthermore, VUE and MFI/MFD can be associated with an adverse neurodevelopmental outcome in the children. For all these entities potential therapy strategies have been reported, which are mainly based on anticoagulation and immunosuppression in subsequent pregnancies.

Topics: Abortion, Spontaneous; Chorionic Villi; Chronic Disease; Female; Fetal Growth Retardation; Fibrin; Histiocytosis; Humans; Infant, Newborn; Infarction; Placenta; Placenta Diseases; Placental Circulation; Pregnancy; Pregnancy Trimester, Third; Recurrence; Risk Factors

The indications of the pathological examination of the placenta are mainly represented by uteroplacental vascular deficiency. The clinical context is often evocative, but it can sometimes be solely an intra-uterine growth retardation or an unexplained in utero fetal death. So, the pathological lesions of this uteroplacental vascular deficiency must be well-known to be correctly interpreted, for none of these lesions is truly specific. The pathological diagnosis is based on a group of macroscopic and microscopic arguments. Various physiopathological mechanisms, often imperfectly known, can be at the origin of an uteroplacental vascular insufficiency, but in the current position, the pathological examination does not allow etiopathogenic orientation. The development of the trophoblastic biopsies gives us access to a new material which, in parallel with the cytogenetic analysis, often allows us, in front of an unexplained intra-uterine growth retardation, to direct the diagnosis towards uteroplacental vascular insufficiency. The histological analysis of the chorionic villous sampling taken precociously during pathological pregnancies is thus a major diagnostic contribution. But especially, this analysis gives access to new information which, in the near future, will enable us to better define the pathological evolution of the lesions of hypoxic chorionic villous and to contribute to a better knowledge of this pathology which, under many aspects, still conceals many mysteries.

Topics: Chorionic Villi; Chorionic Villi Sampling; Cysts; Female; Fetal Death; Fetal Hypoxia; Fibrin; Gestational Age; Humans; Infarction; Necrosis; Organ Size; Placenta; Placenta Diseases; Placental Circulation; Pregnancy; Pregnancy Complications; Trophoblasts; Uterus

Chronic histiocytic intervillositis (CHI) is a rare histopathological lesion in the placenta that is associated with poor reproductive outcomes. The intervillous infiltrate consists mostly of maternal mononuclear cells and fibrin depositions, which are both indicators for the severity of the intervillous infiltrate. The severity of the intervillous infiltrate as well as the clinical outcomes of pregnancy differ between cases. Our objective is to determine the relation between the severity of the intervillous infiltrate and the clinical outcomes of CHI.. Cases of CHI were semi-quantitatively graded based on histopathological severity scores. Hereto, CD68 positive mononuclear cells were quantified, fibrin depositions visualized by both a PTAH stain and an immuohistochemical staining, and placental dysfunction was assessed via thrombomodulin staining.. This study included 36 women with CHI. A higher CD68 score was significantly associated with a lower birthweight. Loss of placental thrombomodulin was associated with lower gestational age, lower birthweight, and a lower placenta weight. The combined severity score based on CD68 and PTAH was significantly associated with fetal growth restriction, and the joint score of CD68 and fibrin was associated with birthweight and placental weight.. More severe intervillous infiltrates in CHI placentas is associated with a lower birth weight and placental weight. Furthermore, this study proposes thrombomodulin as a possible new severity marker of placental damage. More research is needed to better understand the pathophysiology of CHI.

Topics: Birth Weight; Chorionic Villi; Female; Fetal Weight; Fibrin; Gestational Age; Humans; Placenta; Placenta Diseases; Pregnancy; Thrombomodulin

We report a case of a 42-year-old woman (Gravida 1, Para 1) who presented in her third trimester of pregnancy with a photo distributed eruption and arthralgias and was subsequently diagnosed with dermatomyositis. She had an emergency Caesarean section at 34 weeks plus 6 days gestation due to decreased fetal movements and non-reassuring fetal heart rate. Her placenta was sent for histopathology and showed features of massive perivillous fibrin deposition. To our knowledge, this is the first case of MDA-5 positive dermatomyositis in pregnancy with a live delivery.

Topics: Adult; Cesarean Section; Dermatomyositis; Female; Fibrin; Humans; Placenta; Placenta Diseases; Pregnancy; Pregnancy Trimester, Third

Placental parenchymal lesions are commonly encountered and carry significant clinical associations. However, they are frequently missed or misclassified by general practice pathologists. Interpretation of pathology slides has emerged as one of the most successful applications of machine learning (ML) in medicine with applications ranging from cancer detection and prognostication to transplant medicine. The goal of this study was to use a whole-slide learning model to identify and classify placental parenchymal lesions including villous infarctions, intervillous thrombi (IVT), and perivillous fibrin deposition (PVFD).. We generated whole slide images from placental discs examined at our institution with infarct, IVT, PVFD, or no macroscopic lesion. Slides were analyzed as a set of overlapping patches. We extracted feature vectors from each patch using a pretrained convolutional neural network (EfficientNetV2L). We trained a model to assign attention to each vector and used the attentions as weights to produce a pooled feature vector. The pooled vector was classified as normal or 1 of 3 lesions using a fully connected network. Patch attention was plotted to highlight informative areas of the slide.. Overall balanced accuracy in a test set of held-out slides was 0.86 with receiver-operator characteristic areas under the curve of 0.917-0.993. Cases of PVFD were frequently miscalled as normal or infarcts, the latter possibly due to the perivillous fibrin found at the periphery of infarctions. We used attention maps to further understand some errors, including one most likely due to poor tissue fixation and processing.. We used a whole-slide learning paradigm to train models to recognize three of the most common placental parenchymal lesions. We used attention maps to gain insight into model function, which differed from intuitive explanations.

Topics: Female; Fibrin; Humans; Infarction; Machine Learning; Placenta; Placenta Diseases; Pregnancy; Thrombosis

Massive perivillous fibrin deposition (MPVFD) in the placenta is associated with pregnancy complications and maternal disease. The aim of the current study was to contribute with increased knowledge regarding MPVFD by comparing maternal characteristics, obstetric and perinatal outcome and recurrence rate according to the degree of MPVFD.. This retrospective observational study included 141 cases of MPVFD collected between January 2003 to December 2018 in the Stockholm region, Sweden. The extent of fibrin deposition was assessed as low (20-32%), moderate (33-50%) or severe (>50%) according to macroscopic examination.. The study covered 48 placentas with low MPVFD, 41 with moderate and 52 with severe MPVFD. Severe MPVFD was associated with more prematurity than moderate and low MPVFDs (56.3% vs 34.2% and 34.0% respectively, p = 0.05 and p = 0.04). In cases with severe MPVFD, 72.3% of the liveborn infants were growth-restricted compared to 34.2% in the moderate group (p = 0.001) and 52.2% in the low group (p = 0.06). The incidence of intrauterine fetal death was 31.3% in the severe MPVFD group, which was significantly higher than in the low MPVFD group (8.5%, p = 0.01) and twice as much as in cases with moderate MPVFD (15.8%, p = 0.07). 105 subsequent pregnancies after an index pregnancy with MPVFD were identified. The outcome was favourable with a liveborn rate of 91-100%.. The extent of fibrin in the placenta plays a role in pregnancy outcome. Cases with severe MPVFD in the placenta was associated with more prematurity, fetal growth restriction and intrauterine fetal death.

Topics: Adult; Female; Fibrin; Humans; Placenta; Placenta Diseases; Pregnancy; Pregnancy Outcome; Retrospective Studies; Sweden

This study aims at observing placental pathologies in COVID-19 infected women, and analyzing its impact on pregnancy outcome.. This is a descriptive-analytical study done at a tertiary centre of Northern India. All COVID-19 positive pregnant women with gestational age ≥20 weeks, with placental histopathological reporting, were included in this study. A total of 173 COVID-19 pregnant women were included in the study.. Placental abnormalities were noticed in 49·16% of total 179 placentae examined. Maternal vascular malperfusion (27·93%) was the most observed placental pathology followed by villous fibrin deposits (22·90%), fetal vasculopathy (16·75%), and acute inflammation (6·70%). Stillbirths were 22 and NICU admissions were seen in 50 neonates. Abnormal placental abnormalities led to higher stillbirths (p value 0·011) and lower Apgar scores at 1 and 5 min (p-value 0·028; p-value 0·002, respectively). Intervillous fibrin deposits had higher risk associated with lower Apgar score at 1 and 5 min [RR 2·05 (95% CI 1·21-3·48, p-value 0·010) and RR 5·52 (95% CI 2·58-11·81, p-value <0·001), respectively]. RP clot/hemorrhage was also associated with lower Apgar score at 1 and 5 min [RR 2·61 (95% CI 1·52-4·49, p-value 0·002) and RR 3.54 (95% CI 1·66-7·55, p-value 0·001), respectively].. Placental abnormalities in COVID-19 infection were associated with significant higher incidence of unexplained stillbirths, and lower Apgar scores. Although, this is the largest descriptive-analytical study done so far, comparative studies are required to draw a clear conclusion regarding the impact of COVID-19 infection on human placenta and its effect on pregnancy outcomes.

Topics: COVID-19; Female; Fibrin; Humans; Infant; Infant, Newborn; Mothers; Placenta; Placenta Diseases; Pregnancy; Pregnancy Complications, Infectious; Pregnancy Outcome; Stillbirth

Does endometriosis have an effect on the placental histopathology pattern and perinatal outcome in singleton live births resulting from IVF treatment?. Retrospective cohort study evaluating the data on all live births following IVF treatment between 2009 and 2017 at one university-affiliated tertiary hospital. All patients had placentas sent for full gross and histopathology assessment, irrespective of complication status or delivery mode. The primary outcomes of the study included anatomical, inflammation, vascular malperfusion and villous maturation placental disorders. The secondary outcomes included fetal, maternal, perinatal and delivery complications. A multivariate logistic model was used to adjust the results for confounding factors potentially associated with significant placental characteristics.. A total of 1057 live births were included in the final analysis and were allocated to the group of women with endometriosis (n = 75) and those without (n = 982). After adjustment for confounding factors, endometriosis was found to be significantly associated with acute chorioamnionitis with moderate to severe maternal (odds ratio [OR] 2.2, 95% confidence interval [95% CI] 1.1-4.6) and fetal (OR 4.9, 95% CI 1.8-13.1) inflammatory response, placenta previa (OR 3.1, 95% CI 1.2-7.8), subchorionic fibrin deposition (OR 3.4, 95% CI 1.2-9.1), intervillous thrombosis (OR 3.4, 95% CI 1.5-8.1), and fetal vascular malperfusion (OR 5.1, 95% CI 1.4-18.1), as well as with preterm birth (OR 2.5, 95% CI 1.4-4.7).. Endometriosis has a significant impact on the placental histopathology and is associated with a higher incidence of preterm birth.

Topics: Endometriosis; Female; Fertilization in Vitro; Fibrin; Humans; Infant, Newborn; Live Birth; Placenta; Placenta Diseases; Pregnancy; Premature Birth; Retrospective Studies

Massive perivillous fibrin deposition (MPDD) is an uncommon placental lesion which has been associated with an increased risk of adverse pregnancy outcome in retrospective series. The purpose of the study was to evaluate the frequency and consequences of MPFD in pregnancies complicated by fetal growth restriction (FGR).. A cohort study of 355 pregnancies complicated by FGR diagnosed according to standard ultrasonographic criteria, enrolled, followed and delivered at a single obstetric unit. Pathological placental lesions were classified according to the Amsterdam Placental Workshop Consensus. Penalized logistic regression models were used to evaluate the association of MPFD with maternal risk factors, other pathological lesions and neonatal outcome.. Moderate-to-severe MPFD was relatively common among FGR pregnancies and was associated with morphometric modifications of placenta and with an increased risk of severe adverse neonatal outcome.

Topics: Adult; Birth Weight; Chorionic Villi; Cohort Studies; Female; Fetal Growth Retardation; Fibrin; Gestational Age; Humans; Infant, Newborn; Infant, Small for Gestational Age; Male; Placenta; Placenta Diseases; Pregnancy; Pregnancy Outcome; Prognosis; Retrospective Studies; Severity of Illness Index

Massive perivillous fibrin deposition (MPVFD) and chronic intervillositis (CI) are related rare pathological correlates of severe intrauterine growth restriction (IUGR) and fetal loss with high recurrence rates. No standard management has been established.. A patient underwent termination of pregnancy at 21 weeks for severe early onset IUGR. Placental histology showed mixed CI with MPVFD. Several months later, the patient became pregnant and was managed with prednisone and aspirin (ASA) but miscarried at 16 weeks. Placental pathology showed MPVFD and focal CI. For two subsequent pregnancies, she was treated with intravenous immunoglobulin (IVIG), heparin, and ASA. Both pregnancies resulted in healthy near-term deliveries with normal placentas.. IVIG, heparin, and ASA can be an option in patients with recurrent pregnancy loss due to MPVFD and CI.

Topics: Abortion, Habitual; Abortion, Spontaneous; Adult; Anticoagulants; Aspirin; Chorionic Villi; Dalteparin; Female; Fetal Growth Retardation; Fibrin; Humans; Immunoglobulins, Intravenous; Immunologic Factors; Placenta; Placenta Diseases; Platelet Aggregation Inhibitors; Pregnancy

The objectives of the study are to describe the obstetric outcomes associated with massive perivillous fibrin deposition (MFD) compared with a control series and to determine if outcome differs according to the extent of fibrin deposition.. Retrospective case-control study based on placentas analyzed over a consecutive 12-year period. MFD was considered severe if it extended over more than 50% of the placenta and moderate between 25% and 50%.. During the study period, MFD was observed on 71 placentas, 39 severe and 32 moderate. Compared with the 142 control women, the 39 women with severe MFD more often had histories of autoimmune disease and intrauterine fetal death. The case women with MFD were associated with elevated levels of maternal alpha-fetoprotein and with a high risk of severe growth restriction and/or intrauterine death. Compared with the infants with moderate MFD, those with severe MFD had also more abnormal umbilical artery Doppler velocimetry findings and more often intrauterine deaths and lower birthweights.. Regardless of their extent, MFD that covered at least 25% of the placenta was almost always accompanied by severe growth restriction and by a high risk of intrauterine fetal death. Moreover, severe MFD tend to be associated with autoimmune diseases of the mothers, and pregnancies show more often a pathologic Doppler of the umbilical arteries and more often intrauterine fetal death that the moderate form. © 2017 John Wiley & Sons, Ltd.

Topics: Adult; Case-Control Studies; Chemical Precipitation; Chorionic Villi; Female; Fetal Death; Fetal Growth Retardation; Fibrin; Humans; Placenta Diseases; Pregnancy; Pregnancy Outcome; Prognosis; Retrospective Studies; Young Adult

Massive perivillous fibrin deposition (MPFD) is associated with serious complications of pregnancy including recurrent spontaneous abortion, fetal growth restriction, and fetal demise. The aim of this study was to determine whether maternal plasma concentrations of angiogenic/antiangiogenic factors in MPFD differ from those of uncomplicated pregnancies.. This retrospective longitudinal case-control study included MPFD cases (n = 10) and control patients (n = 175) with uncomplicated pregnancies who were enrolled in a longitudinal study and delivered at term. Serial plasma concentrations of placental growth factor (PlGF), soluble endoglin (sEng), and soluble vascular endothelial growth factor receptor (sVEGFR)-1 and -2 were determined by an enzyme-linked immunosorbent assay (cases, n = 28 samples; controls, n = 723 samples). Individual analyte concentrations were averaged across gestational age at specimen collection intervals. Linear mixed models were used to test for differences in log-transformed mean analyte concentrations both overall and as a function of time.. The following results were found: (1) patients with MPFD had a lower mean plasma PlGF concentration (P = .03) and higher mean plasma concentrations of sVEGFR-1 and sEng (both P < .01) than controls, adjusted for potential confounders; (2) the mean plasma concentration of PlGF differed further among cases and controls as a function of gestational age interval (P < .0001); however, mean sVEGFR-1 and sEng group differences as a function of gestational age interval approached but did not reach significance (P = .09 and P = .11, respectively); (3) patients with MPFD had lower mean plasma concentrations of PlGF/sVEGFR-1 (P < .0001) and PlGF/sEng (P < .001): both of these relationships differed further as a function of gestational age interval (both P < .0001); and (4) differences in mean sVEGFR-1, sEng, and the ratios of PlGF to sVEGFR-1 and PlGF to sEng were observed before 20 weeks of gestation.. An imbalance of angiogenic/antiangiogenic factors is present in patients with MPFD prior to the diagnosis. We propose that these changes participate in the mechanisms responsible for adverse pregnancy outcomes in patients with MPFD.

Topics: Abortion, Habitual; Angiogenesis Inducing Agents; Angiogenesis Inhibitors; Case-Control Studies; Female; Fetal Death; Fibrin; Humans; Longitudinal Studies; Placenta Diseases; Pregnancy; Young Adult

Chronic histiocytic intervillositis of unknown etiology (CIUE) is a rare placental inflammatory disease, associated with severe obstetric complications. Its pathophysiologic mechanism remains to be elucidated.. To establish anatomical-clinical correlations to improve our understanding of CIUE pathophysiology.. Retrospective study of all cases of CIUE occurring during a 9-year period in a university tertiary hospital center.. CIUE was diagnosed in 69 pregnancies in 50 different women, after early spontaneous abortions (30.4%), late spontaneous abortions (13.0%), in utero deaths (26.1%), and live births (30.4%). Of 39 fetuses surviving to at least 22 weeks, 24 had severe intrauterine growth restriction (61.5%) and 18 died in utero (46.2%). Twelve in utero deaths occurred before 32 weeks of gestation (66.7%). Substantially elevated alkaline phosphatase levels (>600 IU/L) were observed in 55.6% of cases. Microscopic examination of placentas showed that both spontaneous early abortions and intrauterine growth restriction were significantly associated with more intense fibrin deposits.. A diagnosis of CIUE must be considered in cases of severe obstetric complications. We hypothesize that the elevated alkaline phosphatases (ALP) observed during the pregnancy demonstrate the presence of syncytiotrophoblastic lesions due to histiocytosis in the intervillous space, before fibrin deposits cover them.

Topics: Abortion, Spontaneous; Adolescent; Adult; Alkaline Phosphatase; Chorionic Villi; Female; Fetal Death; Fetal Growth Retardation; Fibrin; Histiocytes; Histiocytosis; Humans; Inflammation; Placenta Diseases; Pregnancy; Premature Birth; Retrospective Studies

Massive perivillous fibrin deposition (MPFD) and maternal floor infarction (MFI) of the placenta are rare related conditions associated with poor perinatal outcome including antepartum stillbirth. The diseases are characterized by pathologic accumulation of fibrinoid deposits that surround the placental villi (in the case of MFI predominantly in the basal regions adjacent to the decidual plate). These findings suggest either overproduction and/or defective clearance of fibrinoid within the intervillous space. Recently genetic polymorphisms of the plasminogen activator inhibitor-1 (PAI-1) gene have been found in association with impaired fibrinolysis in the pelvis predisposing to endometriosis. We hypothesized that polymorphisms in one or more of four genes that regulate fibrinolysis were associated with MPFD and MFI placentas. We retrospectively identified 20 consecutive cases of MPFD/MFI from our placental pathology database and generated 2 random gestational age-matched controls for each case. Clinical charts were reviewed. DNA was extracted from archived paraffin blocks of placental tissue from cases and controls. Single nucleotide repeat polymorphisms (SNPs) in loci within PAI-1 gene, thrombin activated fibrinolysis inhibitor (TAFI) gene, plasminogen activator urokinase (u-PA) gene and plasminogen activator tissue (t-PA) gene were studied using PCR methods. Outcomes in the study group included perinatal death (8), preterm IUGR (6), preeclampsia (4) and only 3 normal term deliveries. A spectrum of placental ultrasound abnormalities was observed. No SNP polymorphism was found to associate with MPFD/MFI. MPFD/MFI are associated with significant abnormal perinatal outcomes but have not been shown to be mediated by polymorphisms in candidate genes that are predicted to impair fibrinolysis in our study.

Topics: Carboxypeptidase B2; Case-Control Studies; Chorionic Villi; Female; Fibrin; Genetic Association Studies; Genotype; Humans; Placenta Diseases; Plasminogen Activator Inhibitor 1; Polymorphism, Single Nucleotide; Pregnancy; Pregnancy Outcome; Retrospective Studies; Reverse Transcriptase Polymerase Chain Reaction; Tissue Plasminogen Activator; Urokinase-Type Plasminogen Activator

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

A small proportion of miscarriage specimens obtained by uterine evacuation exhibit increased perivillous fibrin/oid deposition (PVFD). To understand the significance of this finding, the authors reviewed cases from 5/20/02 to 11/10/04 in which surgical pathologists recognized this finding and documented it in their reports. Of 55 cases initially collected, 29 contained at least 30 villi on the slide with at least 50% of villi showing adherent fibrin/oid, and showed no molar change or extensive coagulative necrosis. Review of these 29 cases identified 2 patterns of fibrin/oid deposition: nodular (8 cases) and diffuse (21 cases). A maternal and gestational age-matched control group was collected (21 cases). The diffuse pattern of PVFD encased villi and had tinctorial characteristics of fibrin. Its pattern is similar to that seen in maternal floor infarction and massive perivillous fibrin deposition. The nodular pattern is an exaggerated form of the nodular deposition of matrix-type fibrinoid seen in normal placentas. Comparison of the 3 groups identified a longer duration of vaginal bleeding before uterine evacuation in the diffuse pattern (P=0.001). One patient had a history of 8 miscarriages, 2 of which were represented in this study. All other obstetrical factors studied showed no significant difference between the 3 groups. Thus, diffuse PVFD in miscarriage specimens is associated with prolonged vaginal bleeding and not with maternal thrombophilia or autoimmune disease. Rarely, a patient showing this pattern may have a history of repeated miscarriages.

Topics: Abortion, Spontaneous; Adult; Chorionic Villi; Female; Fibrin; Humans; Immunohistochemistry; Infarction; Placenta Diseases; Placental Circulation; Pregnancy; Uterus

Massive perivillous fibrin deposition (MPFD) is associated with intrauterine growth retardation and first-trimester and second-trimester spontaneous abortion. Histologically, villi near the maternal interface are completely surrounded by fibrinoid material. This work compared the expression of thrombomodulin (TM) and endothelial protein C receptor (EPCR) in early miscarriage specimens with and without MPFD. Ten specimens with a gestational age of 7-12 weeks (mean 10 weeks) and 10 age-matched miscarriage specimens lacking MPFD were sampled. Formalin-fixed paraffin-embedded sections were stained with monoclonal antibodies against TM and EPCR using an immunoperoxidase method. The slides were independently reviewed by two pathologists using a semiquantitative grading system. Among unaffected villi, there was no difference in staining for TM or EPCR in cases of massive perivillous fibrin deposition compared with the control group. In the MPFD cases, loss of membrane positivity was noted for both TM and EPCR at the junction between normal villous epithelium and villous epithelium with deposition of fibrin. This could imply an underlying defect of trophoblastic protein C activation. Alternatively, it may represent a degenerative change secondary to impedence of oxygen and nutrient supply to the trophoblastic epithelium.

Topics: Abortion, Spontaneous; Adult; Chorionic Villi; Enzyme Activation; Female; Fibrin; Glycoproteins; Humans; Immunoenzyme Techniques; Placenta Diseases; Pregnancy; Pregnancy Trimester, First; Protein C; Thrombomodulin

Massive chronic intervillositis (MCI) is an unusual placental lesion associated with poor fetal growth and adverse pregnancy outcome; it has not previously been associated with spontaneous abortion or recurrent pregnancy loss. This article reports a patient who had 10 spontaneous abortions with repetitious massive chronic intervillositis documented in four of five gestations spanning all three trimesters. Characteristic placental histology induced massive infiltration of the maternal intervillous space by chronic inflammatory cells and fibrin, without associated chronic villitis; the cellular infiltrate was composed predominantly of LCA and CD68 immunoreactive cells with scattered CD45RO positivity, consistent with a monocyte/macrophage population with occasional T lymphocytes. Elevated maternal serum alpha-fetoprotein was documented in two pregnancies. These findings support the concept that this unusual placental lesion may have an immunologic basis, and suggest that MCI may be a histopathologically recognizable cause of recurrent spontaneous abortion.

Topics: Abortion, Habitual; Adult; Antigens, CD; Antigens, Differentiation, Myelomonocytic; Chorionic Villi; Chronic Disease; Female; Fibrin; Humans; Immunohistochemistry; Leukocyte Common Antigens; Macrophages; Male; Monocytes; Placenta Diseases; Pregnancy; Pregnancy Outcome; T-Lymphocytes

Pregnant women are more likely to contract malaria than their non-pregnant counterparts. The aim of this study was to develop a simple classification system for the histopathological diagnosis of placental malaria infection applicable to placentas collected in field conditions. The placentas were classified into four groups depending on the presence and distribution of parasites and malaria pigment: active infection, active-chronic infection, past-chronic infection, not infected. The frequency of parasitized placentas (26.4%) was in keeping with the prevalence of placental parasitaemia documented in epidemiological studies. An additional 29.8% placentas showed pigment in fibrin only, indicating past-chronic infection. Chronic placental malaria infection was most common in primigravidae, possibly reflecting ineffective clearance of parasites from the placenta. Seasonal fluctuations between infection categories support progression of placental infection with delayed clearance of pigment from fibrin. The proposed classification system has allowed diagnosis of different categories of placental malaria infection by two independent observers. A standardized method of diagnosis may enhance understanding of placental pathology and reduced birth weight in malaria infection during pregnancy.

Topics: Adolescent; Adult; Africa, Western; Animals; Antibodies, Protozoan; Birth Weight; Enzyme-Linked Immunosorbent Assay; Female; Fibrin; Humans; Immunoglobulin G; Immunoglobulin M; Incidence; Malaria, Falciparum; Parity; Placenta; Placenta Diseases; Plasmodium falciparum; Pregnancy; Pregnancy Complications, Parasitic; Seasons

Malaria in pregnancy is associated with reduced birth weight. Most pathological studies of placental malaria infection have focused on severe Plasmodium falciparum infection. In the present study of 121 placentas delivered in a rural area of The Gambia, malaria infection was diagnosed in tissue sections using a simple classification system and severity of pathology was ranked semiquantitatively. Deposition of malaria pigment in circulating cells was associated with active infections whereas pigment in fibrin was a feature of active-chronic infections. Primigravidae had higher levels of pigment at all sites, although these observations were not always significant. Thickening of the trophoblast basement membrane occurred in all infection categories but fibrinoid necrosis of chorionic villi was a feature of active and active-chronic infection. Both birth weight and placental weight were increased in infected placentas but widespread trophoblast basement membrane thickening was associated with decreased birth weight. Both birth weight and placental weight decreased with increased fibrinoid necrosis and cytotrophoblast prominence but the results were not significant. By this approach it has been possible to correlate placental pathology with different infection categories and to analyse the pathological features associated with decreased birth weight.

Topics: Adolescent; Adult; Basement Membrane; Birth Weight; Female; Fibrin; Humans; Malaria, Falciparum; Organ Size; Parity; Pigmentation Disorders; Placenta; Placenta Diseases; Pregnancy; Severity of Illness Index

Intra-placental sub-chorionic fibrin deposition is a frequent finding but generally does not involve alterations of hemodynamics or the organ's gaseous metabolism. If the deposition is massive, as in the two cases reported here, delayed fetal growth may occur due to altered placental function. Diagnosis using ultrasound is useful both to identify fibrin plaques and to identify possible fetal hypo-development.

Topics: Adult; Chorionic Villi Sampling; Female; Fibrin; Humans; Placenta Diseases; Pregnancy; Ultrasonography, Prenatal

Maternal floor infarction is a recurring placental disease of ubiquitous perivillous fibrin deposition with obliteration of normal placental architecture. In this case, elevated levels of maternal serum alpha-fetoprotein (AFP) were found as well as a small fetal-maternal bleed. The association between placental disease and elevated maternal serum AFP is discussed.

Topics: Adult; alpha-Fetoproteins; Female; Fibrin; Humans; Infarction; Placenta; Placenta Diseases; Pregnancy; Pregnancy Trimester, Second

This investigation was undertaken to determine the relationship, if any, between peripheral placental separation and idiopathic premature labor. Ninety placentas from prematurely delivered patients (who had had no antepartum bleeding) were examined grossly and microscopically. Criteria for antepartum peripheral placental separation included adherent clot, with fibrin deposition and lamination, as well as polymorphonuclear infiltration and marginal decidual necrosis. Forty-nine placentas showed unequivocal evidence of previous peripheral separation. Another three placentas showed presumptive evidence of previous peripheral separation. It is suggested that this separation is of venous origin, and that it may play a role in the process of premature labor. This is not necessarily a cause and effect relationship.

Topics: Abruptio Placentae; Decidua; Female; Fibrin; Hemorrhage; Humans; Obstetric Labor, Premature; Placenta; Placenta Diseases; Pregnancy

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: Abruptio Placentae; Calcinosis; Female; Fibrin; Hemangioma; Humans; Hydatidiform Mole; Infarction; Placenta; Placenta Diseases; Pregnancy; Thrombosis; Ultrasonography; Uterine Neoplasms

With the advent of gray scale ultrasonography, the internal structure of the placenta can be defined in great detail. Subchorionic sonolucent areas visualized on antepartum sonograms correlate with areas of subchorionic fibrin deposition, hematoma, and cystic degeneration in the term placenta. These lesions are apparently of no clinical significance. However, diffuse intraplacental sonolucent cystic lesions are abnormal and are seen in both hydatidiform mole and hydropic swelling of the placenta.

Topics: Adolescent; Adult; Edema; Female; Fibrin; Humans; Hydatidiform Mole; Placenta; Placenta Diseases; Pregnancy; Ultrasonography; Uterine Neoplasms

In 56 placentas there were fibrin clots in the vessels of the chorionic plate and the stem villi. Fifty infants survived. The fibrin clots in the relatively large placental vessels are considered to be the result of intrauterine shock. A similar pathogenetic concept is postulated as in the well-known diseminated fibrin thromboembolism which is evident in the visceral organs of children who died in the perinatal period. This identification of these fibrin clots in the vessels of the stem villi, especially in cases of so-called risk deliveries, allows the risk for newborn to be determined during their first days of life (hyaline-membrane disease, hemorrhagic diathesis, etc.). One can testify the intrauterine shock by these findings, even in newborn who survive the respiratory distress syndrome.

Topics: Disseminated Intravascular Coagulation; Female; Fibrin; Humans; Hyaline Membrane Disease; Infant, Newborn; Placenta; Placenta Diseases; Pregnancy; Pregnancy Complications, Hematologic; Respiratory Distress Syndrome, Newborn; Shock; Thromboembolism

Topics: Chorion; Extraembryonic Membranes; Female; Fibrin; Humans; Placenta Diseases; 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: Animals; Asphyxia Neonatorum; Bacteria; Erythrocytes; Female; Fetal Death; Fibrin; Haplorhini; Humans; Infant, Newborn; Inflammation; Lung; Monkey Diseases; Placenta Diseases; Pregnancy

Rats were inoculated with viable Salmonella dublin organisms, or a crude S dublin endotoxin, at the fourteenth and nineteenth days of pregnancy. They were killed at intervals up to 96 hours after inoculation, and the pathogenesis of the lesions was compared. At each stage of pregnancy the initial lesions produced by live bacteria and crude endotoxin showed important similarities, confirming the significance of endotoxin in the pathogenesis of placental damage. There were differences in the later stages of the pathogenic process. Comparisons of the process of placental damage at the two stages of pregnancy have suggested that the same mechanism acts throughout the last third of pregnancy and that thrombosis and disseminated intravascular coagulation are not an important part of the mechanism of placental damage.

Topics: Animals; Disseminated Intravascular Coagulation; Endotoxins; Female; Fetal Death; Fibrin; Granulation Tissue; Hemorrhage; Necrosis; Neutrophils; Placenta; Placenta Diseases; Pregnancy; Pregnancy Complications, Infectious; Rats; Salmonella Infections, Animal; Sodium Chloride; Thrombosis; Time Factors; Toxemia; Uterus

Topics: Basement Membrane; Calcinosis; Capillaries; Collagen; Endoplasmic Reticulum; Female; Fibrin; Fibroblasts; Gestational Age; Humans; Infarction; Microscopy, Electron; Placenta; Placenta Diseases; Polyribosomes; Pregnancy; Pregnancy, Prolonged; Time Factors; Trophoblasts

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: Abortion, Spontaneous; Allergy and Immunology; Chorionic Gonadotropin; Decidua; Endometritis; Environment; Estriol; Estrogens; Female; Fibrin; Genetics; Hematoma; Humans; Maternal-Fetal Exchange; Myocardial Infarction; Placenta; Placenta Diseases; Pregnancy; Pregnancy, Prolonged; Staining and Labeling; Thrombosis; Trophoblasts

Topics: Female; Fibrin; Humans; Microscopy, Fluorescence; Necrosis; Placenta; Placenta Diseases; Pregnancy

Topics: Autopsy; Basal Ganglia; Brain; Disseminated Intravascular Coagulation; Female; Fetal Diseases; Fibrin; Humans; Hydrocephalus; Infant, Newborn; Ischemia; Male; Necrosis; Placenta; Placenta Diseases; Plasma Cells; Pregnancy; Thrombosis; Virus Diseases

Infection is well recognized as a complication of intrauterine transfusion. The majority of cases are fortunately mild and consist merely of chorio-amnionitis. The present case, of severe type, resulted from contamination of the donor blood with Acinetobacter calcoaceticus. Spread of infection from foetus to mother has been carefully studied and an entirely new type of lesion in the placenta described. This takes the form of acute villous inflammation with resultant micro-abscess formation beneath the trophoblast layer and eventual rupture into the intervillous space. Attempts at localization are poor.

Topics: Abscess; Alcaligenes; Bacterial Infections; Blood Transfusion, Intrauterine; Coombs Test; Female; Fetal Diseases; Fibrin; Humans; Inflammation; Male; Myocardium; Placenta Diseases; Pregnancy; Pregnancy Complications; Trophoblasts

Topics: Birth Weight; Extraembryonic Membranes; Female; Fibrin; Gestational Age; Humans; Infant, Newborn; Infant, Premature; Male; Maternal-Fetal Exchange; Placenta; Placenta Diseases; Pregnancy

Topics: Female; Fibrin; Fibrinogen; Humans; Labor, Obstetric; Placenta Diseases; Pregnancy; Time Factors

Topics: Birth Weight; Blood Vessels; Female; Fibrin; Gestational Age; Glycosaminoglycans; Hematoma; Humans; Myofibrils; Placenta; Placenta Diseases; Pregnancy; Pregnancy Complications; Rupture, Spontaneous; Thromboembolism; Thrombosis; Umbilical Arteries

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: Chorionic Gonadotropin; Female; Fibrin; Fluorescent Antibody Technique; Humans; Infarction; Placenta; Placenta Diseases; Pregnancy; Pregnancy Complications

Topics: Female; Fibrin; Humans; Methods; Placenta; Placenta Diseases; Pregnancy; Statistics as Topic

Topics: Embryonic and Fetal Development; Female; Fibrin; Hematoma; Humans; Infarction; Maternal Mortality; Maternal-Fetal Exchange; Methods; Placenta; Placenta Diseases; Pregnancy; Radiography; Regional Blood Flow; Thrombosis

Topics: Animals; Benzopyrans; Blood Coagulation Disorders; Blood Coagulation Factors; Blood Platelet Disorders; Budd-Chiari Syndrome; Coronary Disease; Female; Fibrin; Fibrinogen; Fibrinolysis; Heparin; Mice; Microscopy; Microscopy, Electron; Placenta; Placenta Diseases; Pregnancy; Pregnancy Complications; Pulmonary Embolism; Renal Veins; Thrombosis; Veins

Topics: Animals; Autopsy; Cricetinae; Eclampsia; Female; Fetal Death; Fibrin; Humans; Infant Mortality; Infant, Newborn; Kidney Glomerulus; Lung; Maternal-Fetal Exchange; Methods; Microcirculation; Placenta; Placenta Diseases; Pregnancy; Pregnancy Complications; Thromboplastin; Time Factors

Topics: Female; Fibrin; Humans; Infant Mortality; Infarction; Placenta; Placenta Diseases; Pregnancy; Vascular Diseases