fibrin and Fetal-Death

Chronic inflammatory placental disorders are a group of rare but devastating gestational syndromes associated with adverse pregnancy outcome. This review focuses on three related conditions: villitis of unknown etiology (VUE), chronic histiocytic intervillositis (CHI) and massive perivillous fibrin deposition (MPFD). The hallmark of these disorders is infiltration of the placental architecture by maternal immune cells and disruption of the intervillous space, where gas exchange between the mother and fetus occurs. Currently, they can only be detected through histopathological examination of the placenta after a pregnancy has ended. All three are associated with a significant risk of recurrence in subsequent pregnancies. Villitis of unknown etiology is characterised by a destructive infiltrate of maternal CD8+ T lymphocytes invading into the chorionic villi, combined with activation of fetal villous macrophages. The diagnosis can only be made when an infectious aetiology has been excluded. VUE becomes more common as pregnancy progresses and is frequently seen with normal pregnancy outcome. However, severe early-onset villitis is usually associated with fetal growth restriction and recurrent pregnancy loss. Chronic histiocytic intervillositis is characterised by excessive accumulation of maternal CD68+ histiocytes in the intervillous space. It is associated with a wide spectrum of adverse pregnancy outcomes including high rates of first-trimester miscarriage, severe fetal growth restriction and late intrauterine fetal death. Intervillous histiocytes can also accumulate due to infection, including SARS-CoV-2, although this infection-induced intervillositis does not appear to recur. As with VUE, the diagnosis of CHI requires exclusion of an infectious cause. Women with recurrent CHI and their families are predisposed to autoimmune diseases, suggesting CHI may have an alloimmune pathology. This observation has driven attempts to prevent CHI with a wide range of maternal immunosuppression. Massive perivillous fibrin deposition is diagnosed when >25% of the intervillous space is occupied by fibrin, and is associated with fetal growth restriction and late intrauterine fetal death. Although not an inflammatory disorder per se, MPFD is frequently seen in association with both VUE and CHI. This review summarises current understanding of the prevalence, diagnostic features, clinical consequences, immune pathology and potential prophylaxis against recurrence in these

Topics: Abortion, Habitual; Chorioamnionitis; Chronic Disease; COVID-19; Female; Fetal Death; Fetal Growth Retardation; Fibrin; Humans; Placenta; Pregnancy; Pregnancy Outcome; SARS-CoV-2; Syndrome

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

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

A large body of evidence obtained during the past 6 years suggests a significant role for inherited thrombophilia in the development of gestational vascular complications. While the majority of women with thrombophilia will have an uneventful gestation, case-control studies have demonstrated that thrombophilia is more prevalent in cohorts of women with pregnancy loss early onset preeclampsia, placental abruption, and severe intrauterine growth retardation (IUGR). Placental pathological findings in women with thrombophilia are hallmarked by thrombosis and fibrin deposition potentially to a greater degree than in normal pregnancy. Preliminary case-control studies suggest a benefit for prophylaxis with low molecular weight heparins (LMWH), and prospective randomized trials are in progress to define whether LMWH are effective in preventing pregnancy loss in women with thrombophilia and previous fetal wastage.

Topics: Abortion, Habitual; Factor V; Female; Fetal Death; Fibrin; Humans; Hyperhomocysteinemia; Mutation; Placenta; Pregnancy; Pregnancy Complications, Hematologic; Protein C; Prothrombin; Thrombophilia

Defibrination is a fairly common clinical entity seen in a wide variety of clinical disorders. With an awareness of the likely clinical settings, a high degree of suspicion, and widely available sensitive laboratory tests, the diagnosis is ordinarily easily made. The best therapy is usually that which is directed at the underlying disease rather than at the defibrination syndrome itself. In certain symptomatic cases, heparin and/or replacement therapy is indicated, especially if the underlying disorder cannot be immediately successfully treated. On occasion, antifibrinolytic therapy will be useful, always with due regard to the danger of renal cortical necrosis. Depending on the clinical setting, it may be advisable to give heparin with the antifibrinolytic therapy to minimize that danger.

Topics: Adult; Aged; Antifibrinolytic Agents; Blood Cell Count; Blood Coagulation Factors; Disseminated Intravascular Coagulation; Female; Fetal Death; Fibrin; Fibrin Fibrinogen Degradation Products; Fibrinolysis; Heparin; Humans; Male; Postoperative Complications; Pregnancy; Prostatic Neoplasms; Sepsis; Syndrome

Topics: Acute Disease; Animals; Blood Coagulation Disorders; Blood Coagulation Factors; Blood Coagulation Tests; Disseminated Intravascular Coagulation; Embolism, Amniotic Fluid; Female; Fetal Death; Fibrin; Fibrinogen; Fibrinolysis; Hemoglobinometry; Humans; Postpartum Hemorrhage; Pregnancy; Pregnancy Complications, Hematologic; Puerperal Disorders; Shock, Septic; Thrombin

Topics: Abortion, Spontaneous; Blood; Blood Coagulation Tests; Blood Platelets; Cerebral Hemorrhage; Ecchymosis; Factor XIII; Factor XIII Deficiency; Female; Fetal Death; Fibrin; Hematoma; Hemorrhage; Hemorrhagic Disorders; Humans; Infant, Newborn; Placenta; Pregnancy; Pregnancy Complications, Hematologic; Umbilical Cord

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: Abruptio Placentae; Amniotic Fluid; Embolism, Air; Embolism, Fat; Female; Fetal Death; Fibrin; Humans; Inhalation; Pregnancy; Pregnancy Complications, Cardiovascular; Pulmonary Circulation; Pulmonary Embolism; Pulmonary Heart Disease; Thrombophlebitis

Massive perivillous fibrin deposition (MPFD) is associated with adverse pregnancy outcomes and is mainly caused by maternal factors with limited involvement of fetal or genetic causes. We present one consanguineous couple with six fetuses developing Fetal Akinesia Deformation Sequence (FADS) and MPFD, with a possible underlying genetic cause. This prompted a literature review on prevalence of FADS and MPFD.. Fetal ultrasound examination, motor assessment, genetic testing, postmortem examination, and placenta histology are presented (2009-2019). Literature was reviewed for the association between congenital anomalies and MPFD.. All six fetuses developed normally during the first trimester. Thereafter, growth restriction, persistent flexed position, abnormal motility, and contractures in 4/6, consistent with FADS occurred. All placentas showed histologically confirmed MPFD. Genetic analyses in the five available cases showed homozygosity for two variants of unknown significance in two genes, VARS1 (OMIM*192150) and ABCF1 (OMIM*603429). Both parents are heterozygous for these variants. From 63/1999 manuscripts, 403 fetal outcomes were mobilized. In 14/403 fetuses, congenital abnormalities in association with MPFD were seen of which two fetuses with contractures/FADS facial anomalies.. The low prevalence of fetal contractures/FADS facial anomalies in association with MPFD in the literature review supports the possible fetal or genetic contribution causing FADS and MPFD in our family. This study with literature review supports the finding that fetal, fetoplacental, and/or genetic components may play a role in causing a part of MPFDs.

Topics: Arthrogryposis; ATP-Binding Cassette Transporters; Consanguinity; Female; Fetal Death; Fetus; Fibrin; Humans; 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

Maternal floor infarction is a relatively rare condition characterized clinically by severe early onset fetal growth restriction with features of uteroplacental insufficiency. It has a very high recurrence rate and carries a significant risk or fetal demise. Pathological characteristics include massive and diffuse fibrin deposition along the decidua basalis and the perivillous space of the basal plate. We present a case of recurrent maternal floor infarction and propose diagnostic clues as well as potential therapeutic options.

Topics: Adult; Female; Fetal Death; Fetal Growth Retardation; Fibrin; Humans; Infarction; Placenta; Placental Circulation; Placental Insufficiency; Pregnancy; Secondary Prevention; Severity of Illness Index; Up-Regulation; Uterine Diseases

Massive perivillous fibrin deposition (MPFD) and maternal floor infarction (MFI) are related placental lesions often associated with fetal death and fetal growth restriction. A tendency to recur in subsequent pregnancies has been reported. This study was conducted to determine whether this complication of pregnancy could reflect maternal antifetal rejection.. Pregnancies with MPFD were identified (n = 10). Controls consisted of women with uncomplicated pregnancies who delivered at term without MPFD (n = 175). Second-trimester maternal plasma was analyzed for panel-reactive anti-HLA class I and class II antibodies. The prevalence of chronic chorioamnionitis, villitis of unknown etiology, and plasma cell deciduitis was compared between cases and controls. Immunohistochemistry was performed on available umbilical vein segments from cases with MPFD (n = 4) to determine whether there was evidence of complement activation (C4d deposition). Specific maternal HLA-antibody and fetal HLA-antigen status were also determined in paired specimens (n = 6). Plasma CXCL-10 concentrations were measured in longitudinal samples of cases (n = 28 specimens) and controls (n = 749 specimens) by ELISA. Linear mixed-effects models were used to test for differences in plasma CXCL-10 concentration.. (i) The prevalence of plasma cell deciduitis in the placenta was significantly higher in cases with MPFD than in those with uncomplicated term deliveries (40% versus 8.6%, P = 0.01), (ii) patients with MPFD had a significantly higher frequency of maternal anti-HLA class I positivity during the second trimester than those with uncomplicated term deliveries (80% versus 36%, P = 0.01); (iii) strongly positive C4d deposition was observed on umbilical vein endothelium in cases of MPFD, (iv) a specific maternal antibody against fetal HLA antigen class I or II was identified in all cases of MPFD; and 5) the mean maternal plasma concentration of CXCL-10 was higher in patients with evidence of MPFD than in those without evidence of MFPD (P < 0.001).. A subset of patients with MPFD has evidence of maternal antifetal rejection.

Topics: Adult; Chemokine CXCL1; Chorionic Villi; Complement C4; Endothelium, Vascular; Female; Fetal Death; Fetal Growth Retardation; Fibrin; Histocompatibility, Maternal-Fetal; HLA Antigens; Humans; Infarction; Isoantibodies; Pelvic Floor; Placenta; Pregnancy; 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

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

Antiphospholipid syndrome is characterized by recurrent pregnancy loss, thrombosis, and antiphospholipid antibodies. However, some women with clinical features of antiphospholipid syndrome test negative for antiphospholipid antibodies ("antiphospholipid-like syndrome"). Women with antiphospholipid and antiphospholipid-like syndromes have serum immunoglobulin G that harms murine pregnancy, suggesting that the mechanisms of fetal death may be similar in both groups. The objective of our study was to determine whether patients with antiphospholipid and antiphospholipid-like syndromes share pathophysiology by comparing the histology of gestational tissues from these groups.. Placenta and abortion specimens were obtained from 44 pregnancies in 26 women with antiphospholipid syndrome and 37 pregnancies in 21 women with antiphospholipid-like syndrome. Of these, 16 pregnancies with antiphospholipid syndrome and 8 with antiphospholipid-like syndrome were treated with a variety of medications intended to improve pregnancy outcome. Placentas from 31 elective pregnancy terminations and 40 pregnancies complicated by idiopathic preterm delivery served as an additional control group. Twenty histologic parameters were systematically assessed by a single investigator who was blinded to the clinical status of the specimens. Histopathologic findings were compared among groups using multivariate logistic regression analysis.. Antiphospholipid syndrome pregnancies included 15 spontaneous abortions, 13 fetal deaths, and 16 live births. Pregnancies in the antiphospholipid-like syndrome group resulted in 5 spontaneous abortions, 30 fetal deaths, and one live birth. Gestational tissues from antiphospholipid and antiphospholipid-like syndrome pregnancies were similar for every histologic feature tested. Decidua from women with both antiphospholipid and antiphospholipid-like syndromes had more necrosis, acute and chronic inflammation, and vascular thrombus compared to controls. Placental tissue from antiphospholipid and antiphospholipid-like syndrome pregnancies showed more infarction, intravascular fibrin deposition, syncytial knot formation, and fibrosis than controls. Histologic features were variable within groups. There were no histologic differences in tissues from live births and pregnancy losses, or in treated and untreated pregnancies.. Placental histopathology is similar in antiphospholipid and antiphospholipid-like syndrome pregnancies, suggesting that these disorders may share pathophysiology. Histologic findings in women with APS are non-specific and may not differentiate between women with APS and APS-like syndromes.

Topics: Abortion, Spontaneous; Adult; Antibodies, Antiphospholipid; Antiphospholipid Syndrome; Chorionic Villi; Decidua; Female; Fetal Death; Fibrin; Fibrosis; Humans; Inflammation; Logistic Models; Necrosis; Placenta; Pregnancy; Thrombosis; Trophoblasts

To establish the incidence, recurrence rate and consequences of massive perivillous fibrinoid.. Retrospective analysis of the histology of all placentas with a diagnosis of massive perivillous fibrinoid between 1991 and 1998, together with the maternal case records.. The histopathology department of the Rotunda Hospital, Dublin, Ireland.. A relatively homogeneous group of pregnant women in the northern part of Dublin City, which is the catchment area for the Rotunda Hospital, delivered between 1991 and 1998.. Retrospective review of archival placental pathology and maternal charts.. The incidence of massive perivillous fibrinoid, perinatal outcome and recurrence rate.. The incidence of massive perivillous fibrinoid was 0.028%, with a recurrence rate of approximately 18%. All the infants suffered intrauterine growth restriction; there was a 31% fetal loss rate and a 33% preterm delivery rate.. Massive perivillous fibrinoid is associated with intrauterine death, intrauterine growth restriction and preterm delivery. It has a significant recurrence rate and both the clinical findings of intrauterine growth restriction and the postmortem findings imply a syndrome of chronic placental insufficiency.

Topics: Abortion, Habitual; Adult; Chorionic Villi; Female; Fetal Death; Fetal Growth Retardation; Fibrin; Gestational Age; Humans; Microscopy, Electron; Obstetric Labor, Premature; Placental Insufficiency; Pregnancy; Recurrence; Retrospective Studies

Blood coagulation in vivo is initiated by factor VII (FVII) binding to its cellular receptor tissue factor (TF). FVII is the only known ligand for TF, so it was expected that FVII-deficient embryos would have a similar phenotype to TF-deficient embryos, which have defective vitello-embryonic circulation and die around 9.5 days of gestation. Surprisingly, we find that FVII-deficient (FVII-/-) embryos developed normally. FVII-/- mice succumbed perinatally because of fatal haemorrhaging from normal blood vessels. At embryonic day 9.5, maternal-fetal transfer of FVII was undetectable and survival of embryos did not depend on TF-FVII-initiated fibrin formation. Thus, the TF-/- embryonic lethal and the FVII-/- survival-phenotypes suggest a role for TF during embryogenesis beyond fibrin formation.

Topics: Animals; Blood Coagulation; Culture Techniques; Embryonic and Fetal Development; Factor VII; Female; Fetal Death; Fibrin; Gene Targeting; Hemorrhage; Hemostasis; Maternal-Fetal Exchange; Mice; Mice, Inbred C57BL; Mutagenesis; Pregnancy; Thromboplastin

Microscopical examination of 50 placentas of stillborn infants and 50 of normal infants (controls) was performed for detection of thrombosis in the stem fetal vessels. Fresh fibrin thrombi occurred with equal frequency in stillborns and normal infants, suggesting that these thrombi are not necessarily of pathological significance. In normal infants they might be related to clamping of the umbilical cord. In placentas of normal infants and of stillbirths with 1 day of placental retention (P.R.) organizing thrombi were rare and when occlusive they were related to avascular villi, which suggests that they were pre-mortem in origin. By contrast organizing thrombi were found in 78.5% of placentas of stillbirths with 2-7 days of P.R, where arterial occlusive thrombi were rarely associated with avascular villi. With over 7 days of P.R. they were almost fully organized. These findings suggest that most organizing thrombi in placental vessels of macerated stillbirths are probably post-mortem clots in process of organization by the still living placenta and should therefore not be attached pathological significance.

Topics: Constriction, Pathologic; Female; Fetal Death; Fibrin; Humans; Placenta; Pregnancy; Thrombosis

In an attempt to determine the frequency, course, and outcome of maternal floor infarcts, 39,215 placentas and pregnancies were reviewed. The disorder is somewhat misnamed, because it is characterized by heavy deposition of fibrin in the decidua beneath the placenta rather than by arterial occlusion and ischemic necrosis of villi. The fibrin in floor infarcts often extends into the intervillous space, where it envelops villi, causing them to become atrophic. The disorder was relatively frequent in the present study, being present in nearly one of every 200 placentas. Mortality was high, with 17 per cent of the fetuses being stillborn. It may be a recurrent disorder, because 50 per cent of the gravidas with floor infarcts, compared with 27 per cent of control subjects (P less than 0.001), had had prior abortions and stillbirths. Damage to the decidua basalis by ischemia or infection may initiate many floor infarcts. Atheroma in the decidual arteries, foci of decidual necrosis, and histologic evidence of low uteroplacental blood flow were more frequent in patients with floor infarcts. Low maternal blood volume may contribute to the low blood flow because maternal hemoglobin values were often abnormally high in gravidas in whom floor infarcts developed. Acute chorioamnionitis, which can damage the decidua, had twice the expected frequency in gravidas with floor infarcts.

Topics: Decidua; Female; Fetal Death; Fetal Growth Retardation; Fibrin; Humans; Infarction; Menstruation Disturbances; Placenta; Pregnancy; Pregnancy Complications, Cardiovascular

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

Topics: Female; Fetal Death; Fetal Membranes, Premature Rupture; Fibrin; Humans; Obstetric Labor, Premature; Pregnancy; Pregnancy Trimester, Second; Tissue Adhesives

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

Soluble fibrin monomer complexes have been determined in approximately 500 obstetric patients by protamine sulfate precipitation, as a test for intravascular coagulation. The incidence of positive fibrin monomer was less than 1% in 139 samples drawn during normal pregnancy. In confirmed abruptio placentae, 84% of samples were positive, but other sources of antepartum bleeding were negative. Positive results were obtained in 24% of samples from patients between 3 and 48 hours after injection of hypertonic saline for second trimester abortion, 33% were positive by only 3% were positive after administration of prostaglandins. The test for intravascular coagulation is simple and rapidly carried out. The results correlated well with the clinical condition of patients with disseminated intravascular coagulation. However, the test is usually negative in patients with thromboembolic phenomena.

Topics: Abruptio Placentae; Blood Coagulation Tests; Disseminated Intravascular Coagulation; Female; Fetal Death; Fibrin; Fibrinogen; Humans; Pregnancy; Pregnancy Complications; Pregnancy Complications, Hematologic; Pregnancy Trimester, First; Pregnancy Trimester, Second; Pregnancy Trimester, Third; Prostaglandins; Protamines; Thromboembolism

In course of overdue pregnancy in rats, produced by application of synthetic gestagens the intrauterine death rate rises, when the gestation time is more than 23 days. Placentas of 47 macereted fetus rats we have investigated. The pathologic-anatomical picture of the placenta characterized by collaps and following regression of the peripheral fetal blood system. Furthermore, there are narrowing processes in great fetal vessels. In the maternal sinus occurs fibrin. The labyrinth of the placenta inclines by production of collagen fibers to a homogenous structure. The trophoblastic epithel is less differentiated. These findings in rat placentas we have compared with those in human placentas in cases of fetal maceration. The worth of these changes for differentiation of intravital against postmortal regressive processes is evident.

Topics: Animals; Epithelial Cells; Female; Fetal Death; Fibrin; Gestational Age; Glycogen; Placenta; Pregnancy; Pregnancy, Prolonged; Rats; Thrombosis; Trophoblasts

Lesions are described in the vocal cords of an unselected group of 91 infants dying as "cot deaths", 11 stillbirths and 107 infants and children dying from conventional diseases. The lesions have been classified into six types. After allowances for the effects of intubation, the same incidence and type of change was present in all but the stillbirths. This argues against them being a specific pathogenic mechanism confined to the cot death situation. The aetiology and pathogenesis are unexplained but indicate the existence of an unsuspected laryngeal disorder that merits further study in mechanism leading to child death.

Topics: Autopsy; Basement Membrane; Female; Fetal Death; Fibrin; Humans; Infant; Infant, Newborn; Intubation, Intratracheal; Laryngeal Diseases; Necrosis; Pregnancy; Sudden Infant Death; Ulcer; Vocal Cords

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: Abortion, Induced; Blood Coagulation Tests; Disseminated Intravascular Coagulation; Factor V; Factor VIII; Female; Fetal Death; Fetal Heart; Fibrin; Fibrinogen; Humans; Hypertonic Solutions; Labor, Obstetric; Methods; Postpartum Period; Pregnancy; Prothrombin Time; Sodium Chloride; Time Factors

Topics: Disseminated Intravascular Coagulation; Female; Fetal Death; Fibrin; Humans; Infant, Newborn; Infant, Newborn, Diseases; Liver; Pregnancy; Thromboembolism

Topics: Autopsy; Blood Pressure; Body Temperature; Delivery, Obstetric; Extraembryonic Membranes; Female; Fetal Death; Fibrin; Gestational Age; Humans; Infant, Newborn; Infant, Newborn, Diseases; Medical History Taking; Necrosis; Pregnancy; Prenatal Care; Time Factors

Topics: Afibrinogenemia; Female; Fetal Death; Fibrin; Fibrinogen; Humans; Placenta; Pregnancy; Uterus

Topics: Abruptio Placentae; Adolescent; Adult; Arteries; Blood Coagulation Tests; Cesarean Section; Delivery, Obstetric; Female; Fetal Death; Fibrin; Fibrinogen; Fibrinolysis; Humans; Pregnancy; Uterus; Veins

Topics: Afibrinogenemia; Blood Coagulation Disorders; Female; Fetal Death; Fibrin; Humans; Hysterectomy; Pregnancy; Pregnancy Complications, Hematologic

The levels of fibrin, fibrinogen degradation products (F.D.P.) in the serum were investigated in normal pregnancy and parturition, after caesarean section, and in patients with abruptio placentae, eclampsia, intrauterine death, and post-partum haemorrhage. No significant change occurred during normal pregnancy, but a highly significant increase was found during labour and again during the first week after normal delivery. After caesarean section the levels of F.D.P. were increased two to four hours after operation, and substantially higher levels were found three to eight days after operation than after normal delivery. High levels of F.D.P. were associated with abruptio placentae and eclampsia, and increased levels after intrauterine death and post-partum haemorrhage.An excess of F.D.P. with diminished or normal systemic fibrinolytic activity suggests that local intravascular fibrin deposition and fibrinolysis occur in normal parturition and in these complications of pregnancy. The very high levels of F.D.P. found in abruptio placentae will be important in the pathogenesis of the defective haemostasis that may accompany this complication.

Topics: Abruptio Placentae; Cesarean Section; Eclampsia; Female; Fetal Death; Fibrin; Fibrinogen; Fibrinolysis; Hemostasis; Humans; Labor, Obstetric; Postpartum Hemorrhage; Pregnancy; Pregnancy Complications

Topics: Abortion, Septic; Abruptio Placentae; Antibodies; Antigens; Blood Coagulation Disorders; Eclampsia; Embolism, Amniotic Fluid; Female; Fetal Death; Fibrin; Fibrinogen; Fibrinolysis; Hemostasis; Humans; Immunoelectrophoresis; Kidney Glomerulus; Lung; Pregnancy; Pregnancy Complications, Hematologic; Spleen; Thrombelastography

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

Topics: Adult; Chemical Precipitation; Choroiditis; Diseases in Twins; Endotoxins; Escherichia coli Infections; Extraembryonic Membranes; Female; Fetal Death; Fetal Diseases; Fibrin; Humans; Infant, Newborn; Infant, Premature, Diseases; Obstetric Labor, Premature; Photomicrography; Placenta; Pregnancy; Pregnancy Complications, Infectious; Rupture; Shwartzman Phenomenon

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

Topics: Adrenal Gland Diseases; Adult; Afibrinogenemia; Arteries; Cerebral Hemorrhage; Female; Fetal Death; Fetal Diseases; Fibrin; Humans; Infant, Newborn; Liver Diseases; Portal Vein; Pregnancy; Splenic Diseases; Thromboembolism; Umbilical Arteries; Umbilical Cord