Intervillous Thrombosis Research Articles

Diagnosis of Placental Abruption: Relationship Between Clinical and Histopathological Findings

Despite intensive investigation, it is unclear whether the diagnosis of placental abruption should be based on established clinical criteria or histopathological findings. Although the vast majority of placental abruption cases appear to have a chronic etiology, it also remains speculative as to whether abruption is an acute or chronic process. The aim of the present multicenter, case-control study was to assess the concordance between clinical and histopathological diagnostic indicators of placental abruption. A secondary aim was to investigate acute and chronic histological lesions associated with clinical abruption. The clinical and histologic criteria for abruption were compared using data obtained from the New Jersey-Placental Abruption Study. The study subjects, 162 women with a confirmed clinical diagnosis of placental abruption, were matched with 173 controls without placental abruption. Criteria for the clinical diagnosis of placental abruption included painful vaginal bleeding accompanied by nonreassuring fetal status, uterine hypertonicity, evidence of clinically significant retroplacental bleeding, or clot(s) or placental abruption diagnosed on prenatal ultrasound. The pathological criteria for a diagnosis of abruption included hematoma with or without recent or old infarctions, foci of villous compression, fibrin deposition, and hemosiderin-laden histiocytes in cases with older hematomas. Histologic lesions were grouped as acute or chronic histologic lesions. Acute lesions included chorioamnionitis, funisitis, acute deciduitis, meconium-stained membranes associated with amnion necrosis and pigmented macrophages, villous stromal hemorrhage, and villous edema. Chronic lesions included chronic deciduitis, maternal floor decidual necrosis, decidual vasculopathy, placental infarction, villous mal-development with delayed or accelerated maturation, hemosiderin deposition, intervillous thrombosis, and villitis. Of the 162 clinically diagnosed cases, only 30.2% (n = 49) were confirmed as placental abruption based on gross or histological findings, whereas the specificity for a histologic confirmation of abruption was 100%. Among clinically diagnosed cases, the most common indication for a clinical diagnosis of abruption was evidence of retroplacental clot(s) or bleeding (77.1%). Two chronic lesions, placental infarction and decidual vasculopathy, were significantly associated with abruption, but no acute lesions were significantly associated with abruption. The investigators conclude from these finding that there is poor concordance between the clinical and pathological diagnosis of placental abruption. The diagnosis of abruption should be based on clinical criteria such as evidence of retroplacental bleeding or clot(s), ultrasound visualization of abruption, or painful vaginal bleeding accompanied by either nonreassuring fetal status or uterine hypertonocity.

Severe Preeclampsia With and Without HELLP Differ With Regard to Placental Pathology

The aim of the present study was to evaluate the histopathology in placentas from patients with severe preeclampsia with and without hemolysis, elevated liver enzymes, and low platelets (HELLP) syndrome. An additional aim was to compare the prevalence of infants born small for gestational age in the 2 groups. The study is retrospective and includes 178 women who have been diagnosed at the Karolinska University Hospital Huddinge or at the Free University Medical Center between 2000 and 2005 with severe preeclampsia. A total of 96 women had severe preeclampsia without signs of HELLP (preeclampsia group), whereas 82 fulfilled the criteria for having HELLP syndrome (HELLP group). Infarction (P=0.014), intervillous thrombosis (P<0.001), and abruption (P=0.002) were more common in the preeclampsia group than in the HELLP group. There was no statistically significant difference in the frequency of accelerated villous maturation (P=0.61), decidual arteriopathy (P=0.27), or chorioamnionitis (P=0.61). Furthermore, there was a higher mean placental weight, adjusted for gestational age, in the Swedish HELLP material than in the preeclampsia group (P<0.001). Finally, mothers in the preeclampsia group gave birth significantly more often to small for gestational age babies than mothers suffering from HELLP syndrome (P<0.001). The histopathologic profile and the range of placental lesions were partly different in the preeclampsia and HELLP patients. Considering the central role that placenta seems to have in preeclampsia, the present result might suggest that different underlying pathogenetic mechanisms and courses can be in play in patients with preeclampsia and HELLP syndrome.

OP10.14: Placental cyst or extra‐amniotic pregnancy?

JM is a 22 year old G2P1 who initially had a 13 week ultrasound which showed a thick membrane adjacent to the superior edge of the placenta, most likely representing a marginal hematoma. A 21 week ultrasound showed normal fetal anatomy, normal amniotic fluid and a normal left anterior placenta. A follow up 28 week ultrasound showed the following: turbid amniotic fluid filled with echoreflections, thick and heterogeneous placenta, numerous cystic structures emanating from the placenta, with no vascular flow, easily deformable by fetal body parts. The differential diagnosis at this point was: placental cyst (s), late amniotic rupture (extra-amniotic pregnancy), previously undiagnosed early amnion rupture with amniotic bands. A follow up 33 week ultrasound showed good growth (45 percentile) and normal amniotic fluid. A fetal echo showed mild tricuspid regurgitation and mild narrowing of the ductus arteriosis. A maternal hyperoxygenation pulmonary vascular test showed normal pulmonary vascular reactivity in response to oxygen, thus decreasing the likelihood for pulmonary hypoplasia. At 36 weeks, the fetus was less than the 10th percentile for size with preservation of the head/abdomen ratio. The fetus was tested with umbilical artery Doppler, NST and AFI. She was induced at 39 weeks and delivered a healthy neonate weighing 5 lbs, 9 ounces. There were no gross anomalies and no evidence of amniotic bands. The placenta grossly showed a 2 × 2 × 3 centimeter placental cyst on the fetal side. Placental pathology reported a marginal hematoma, multiple subchorionic cysts, intervillous thrombosis and old hemorrhage in the membranes. Pathology noted that while not specific, marginal hematoma and evidence of old hemorrhage are characteristic of extramembranous pregnancy.

Maternal vasculopathy and histologic diagnosis of preeclampsia: Poor correlation of histologic changes and clinical manifestation

The purpose of this study was to evaluate the frequency of maternal vasculopathy and to determine the usefulness of placental examination in correlation with clinical manifestation of pregnancy-induced hypertension. We investigated 350 pregnancy-induced hypertension placentas over a 2.5-year period (January 2002-June 2004) to identify the potential usefulness of the maternal vasculopathy in histologic diagnosis and corroboration of clinical preeclampsia. This study was carried out at West Virginia University Ruby Memorial Hospital, where 1271 placentas were examined macroscopically and microscopically for the period. The presence or absence of vascular changes, infarctions, thrombosis, abruption, chorangiosis, and chorioamnionitis were investigated for each placenta with the clinical diagnosis of preeclampsia or pregnancy-induced hypertension. Two types of vascular changes that are characteristic of pregnancy-induced hypertension, namely maternal atherosis and fibrinoid medial necrosis, were found in 21.4% of the placentas (75/350 placentas). These vascular changes were found mainly in the decidua capsularis of the membrane rolls, not on the decidua basalis of the maternal floor. There were more placental infarctions within these placentas (32.3%; 113/350 placentas). Intervillous thrombosis was 18.9% (66/350 placentas); microscopic abruption was 6.3% (22/350 placentas); chorangiosis was 10.9% (38/350 placentas), and chorioamnionitis was 8.6% (30/350 placentas). These findings demonstrate that the maternal vascular changes that are characteristic of pregnancy-induced hypertension are found in approximately 1 of 5 pregnancy-induced hypertension placentas. Examination of pregnancy-induced hypertension placentas should be based on a combination of a number of histologic changes. Furthermore, the decidua capsularis of the fetal membrane roll, rather than the decidua basalis of the maternal floor, of the placenta should be examined for these maternal vascular changes.

Characteristics of histopathological and ultrastructural features of placental villi in pregnant Nepalese women

The placenta is an important functional unit for gas transfer between mother and fetus. The placental membrane, consisting of trophoblast layer interposed between maternal and fetal blood, plays an active role for intensity of respiration, but no morphological evidence has been documented. Until now, it has been reported that fetal growth retardation and increased fetal mortality rate usually could be seen at high altitude. In an attempt to find the cause of high perinatal mortality rate in Nepal, this study was undertaken to examine pathologically about 1000 Himalayan placentas obtained in Nepal and Tibet since 1977, and the results were compared with those of 5500 Japanese placentas at Saitama Medical School since 1990. In this study, characteristics of ultrastructural features of the Nepalese placental villi investigated in recent years are reported. (1) The gross characteristics of placental pathology in the Himalayan group were represented by marked subchorionic fibrin deposits and increased chorionic cysts in contrast to low incidence of intervillous thrombosis compared with those of the Japanese group. (2) As characteristics of histological findings of the placental villi between Himalayan and Japanese groups, the incidence of chorangiosis and chorangioma in the Himalayan group was significantly higher than that in the Japanese group. (3) Accompanying an increase of vasculosyncytial membrane (VSM) in the villi, thickness and separation of basement membrane of the syncytium in addition to increased apoptosis of syncytial cell nuclei were recognized. (4) As characteristic ultrastructural features of chorionic villi of Nepalese placentas, an increase of mitochondria and cystic formation of rough endoplasmic reticulum (rER), in addition to appearance of lamellar bodies similar to alveolar epithelial type II cell in organellae of the syncytium, were observed. These ultrastructural changes of the placental villous capillaries may be ascribed to hypervascularization caused by the chronic hypoxic state. It is, therefore, presumed that trophoblast cells may play an important role for gas transfer mechanism under such a hypoxic state at high altitude.

Defective endovascular trophoblast invasion in primary antiphospholipid antibody syndrome-associated early pregnancy failure

Primary antiphospholipid antibody syndrome (PAPS) is an established cause of recurrent pregnancy loss, traditionally presumed to be due to 'intraplacental thromboses'. This study examines products of conception (POC) from early pregnancy failures to investigate the mechanism of pregnancy loss. POC from patients attending a recurrent miscarriage clinic and from terminations of pregnancy for non-medical reasons were examined histologically with particular regard to the presence or absence of vascular or intervillous thromboses and decidual endovascular trophoblast invasion. There were 31 PAPS-positive, 50 PAPS-negative, 34 aneuploid and 20 control cases at 6-14 weeks gestation. Villous morphology and frequency of intervillous thrombosis were not different among groups. Normal intradecidual endovascular trophoblast invasion was identified significantly less frequently in PAPS+ cases (24%), compared with controls (75%), aneuploid (53%), or PAPS- cases (61%; Z = -3.0, P < 0.01). In all cases there was apparently normal interstitial extravillous trophoblast invasion. Defective decidual endovascular trophoblast invasion, rather than excessive intervillous thrombosis, is the most frequent histological abnormality in PAPS+ associated early pregnancy loss. Furthermore, endovascular trophoblast invasion is not significantly reduced in the majority of fetal aneuploidy-associated pregnancy failures.

Increased Frequency of Genetic Thrombophilia in Women With Complications of Pregnancy

Background Obstetrical complications such as severe preeclampsia, abruptio placentae, fetal growth retardation, and stillbirth are associated with intervillous or spiral-artery thrombosis and inadequate placental perfusion. Whether these complications are associated with an increased frequency of thrombophilic mutations is not known. Methods We studied 110 women who had one of the above-mentioned obstetrical complications and 110 women who had one or more normal pregnancies. The women were tested several days after delivery for the mutation of adenine to guanine at nucleotide 506 in the factor V gene (factor V Leiden), the mutation of cytosine to thymine at nucleotide 677 in the gene encoding methylenetetrahydrofolate reductase, and the mutation of guanine to adenine at nucleotide 20210 in the prothrombin gene. Two to three months after delivery the women were tested for deficiency of protein C, protein S, or antithrombin III and for the presence of anticardiolipin antibodies. Results The mutation at nucl...

Nitric Oxide Synthase Activity and Doppler Parameters in the Fetoplacental and Uteroplacental Circulation in Preeclampsia

Objective: We investigated the hypothesis that changes in blood flow in the uteroplacental and fetoplacental circulation in preeclampsia are associated with an abnormality of placental or uterine placental bed nitric oxide (NO) synthesis.Methods: We measured pulsatility indices on Doppler waveform analysis from uterine and umbilical arteries in 20 patients with preeclampsia and 14 healthy pregnant controls before elective cesarean section. During cesarean section, biopsies from the uterine placental bed and the placenta were taken and the nitric oxide synthase (NOS) activity was measured by the [3H] L-arginine-[3H] L-citrulline conversion assay in these samples.Results: The NOS activity was significantly lower in the uterine placental bed in comparison to the placental tissue (p < 0.01). Placental NOS activity was similar between patients with preeclampsia and healthy controls and in the groups with either a pathological or a normal Doppler flow in the umbilical artery. In the uterine placental bed however, NOS activity from patients with preeclampsia was significantly lower (p 0.01), whereas the blood flow resistance in the uterine arteries was elevated (p < 0.01) in comparison to healthy controls.Conclusions: Our data show that pathological Doppler waveforms in the uterine arteries of patients with preeclampsia are paralleled by diminished NOS activity in the uterine placental bed. Therefore, the compromised NO production in the uterine placental bed may play an important role in the impaired uteroplacental blood flow and potentially in some pathological features of preeclampsia such as intervillous thrombosis formation and fetal growth retardation.

Transient Recurrent Venous Phenomenon

The placenta is an important part of every obstetric ultrasound examination, but its evaluation is often underemphasized. Important abnormalities of the placenta can be detected by ultrasound/p=m-/some of them before they adversely affect the fetus. Most of these abnormalities are vascular and include subchorionic hemorrhage, intervillous thrombosis, and placental abruption. The authors present a placental vascular anomaly not described previously. A transiently filling and emptying retroplacental and subchorionic space, corresponding with venous flow, is described by the authors. Throughout an 18-month period, three cases were observed. The pregnancy outcomes were good in all cases, with healthy neonates at birth. The clinical course and pregnancy outcome of these three cases are described.

A clinicopathological aspect of chorionic villous hemorrhage leading to formation of intervillous thrombosis.

Recently it was reported that chorionic villous hemorrhage (CVH) had a significant association with retroplacental hemorrhage (RPH). In this study, to determine whether CVH has a correlation with RPH or intervillous thrombosis (IVT), placentas associated with CVH were clinico-histopathologically investigated and compared to those with IVT. Obstetric complications in 32 cases with CVH were compared with 258 cases with IVT. Placental abruption was significantly higher (18.7%) in the CVH group than in the IVT group (5.03%) and the incidences of intrauterine fetal death (IUFD) as well as intrauterine growth retardation (IUGR) were also significantly higher (18.7% and 9.37%) in the CVH group than in the IVT group (3.10% and 2.32%). Of the pathological characteristics of the placentas with CVH, IVT was found in 46.8%, but marginal or retroplacental hemorrhages were seen in 34.3%, compared to 14.2% of the IVT group. Premature infants with low birth weight (under 2000 g) and before 36 weeks of gestation were born in 53.1% and 34.3% of cases with CVH placentas. CVH was not only located near the basal plate of the placentas and decidual hemorrhages, but was also highly associated with chorangiosis in 75% of cases. Using histological and ultrastructural studies in CVH cases, villous stroma was filled with fetal erythrocytes and leakage of blood cells was observed through a disruption of the trophoblast layer of hemorrhagic villi. In conclusion, it is suggested that CVH may rather be related to formation of the intervillous thrombosis than to RPH.

Two fetal deaths associated with maternal sepsis and with thrombosis of the intervillous space of the placenta

The placental pathology in two second trimester fetal losses associated with mild maternal disseminated intravascular coagulation are reported. Case one had a dental abscess, a leukocytosis of 36 300 white blood cells/m, and evidence of mild consumptive coagulopathy at 20 weeks. Case two had septic findings including disseminated intravascular thrombosis associated with pyelonephritis. The placentae had extensive intervillous thrombosis at the periphery of spiral arterial flow. It is hypothesized that in mild disseminated intravascular coagulation, the trophoblast inhibits fibrinolysis, favouring thrombosis perhaps due to production of plasminogen activator inhibitor.

Placental cavities

To study placental cavities by gross and microscopic examination and ultrasonography and their frequency with various epidemiologic factors and intervillous thrombosis. After formalin fixation, interval sections of 567 placentas were prepared to search for cavities and intervillous thrombosis. Cavities were subjected to histologic and ultrasonographic examinations. Frequency of cavities with diameter of 1 cm or more was 34.9% in 567 mature placentas. Frequency of cavities was significantly higher in heavy, thick placentas associated with male fetuses. Histologic examination revealed villus laceration in cavities and syncytial cells, isolated chorionic villi, or air bubbles in placental fetal veins. All 82 placentas with cavities showed villus lacerations in the cavities and air bubbles in the fetal veins. Intervillous thromboses in fetal lobules were located only in the cavities. Cavities were first found by ultrasonography at a mean gestational age of 30.9 +/- 3.8 weeks. Ultrasonography did not always differentiate accurately between intervillous thrombosis and cavities. Placental cavities were found significantly more often in heavy, thick placentas associated with male fetuses. Strong uterine contractions during placental detachment could produce villus laceration in cavities, following contamination by air bubbles and isolated villus tissue in the fetal veins. Placental cavities are vulnerable to villus laceration. Intervillous thrombosis occurred only in cavities.

Sonography of the placenta with emphasis on pathological correlation

The placenta is a most interesting but unfortunately often ignored and misunderstood organ. Included in its many functions are fetal oxygenation and nutrition as well as a myriad of endocrinological contributions and protein synthesis. The sonologist is strongly encouraged to study this amazing structure with ultrasound because significant pathology afflicts the placenta, often before affecting the fetus. Placental abnormalities, therefore, can be an “early warning system” for fetal problems. Recognition of clinically important lesions (abruption, accreta) as well as important anatomical variants (intervillous thrombosis, septal cyst) is crucial for the physician who performs and interprets prenatal ultrasound. This article discusses the common abnormalites of the placenta and highlights some correlative pathological processes, which will serve to enhance the reader's understanding of sonographic findings. A practical approach is presented with respect to assessment of the hypoechoic lesion, placental infarction, thick placenta, placenta previa, abruption, placenta accreta, and placental tumors.

Chorangiosis and chorangioma in three cohorts of placentas from Nepal, Tibet, and Japan.

It has been reported that both chorangiosis and chorangioma are increased in placentas at high altitudes. In this study, 1.14% of 2448 Japanese placentas obtained at 30-300 m had chorangiosis or chorangioma, compared with 3.24% of the Nepalese placentas (1300-3000 m) and 9.09% of the Tibetan samples (3800-4200 m). The incidence of both pathologies was significantly higher in the Himalayan groups than those of the Japanese group (P < 0.05). Obstetric complications of the 28 Japanese placentas with chorangiosis and chorangioma included Caesarean section 16 (57.1%), abruptio placentae 2 (7.14%), intrauterine growth retardation 3 (10.7%), intrauterine fetal death 4 (14.2%) and placenta praevia 4 (14.2%). Four infants (14.2%) had Apgar scores ranging from 0 to 3. Among 48 Himalayan placentas with chorangiosis and chorangioma, incidence of marked subchorionic fibrin was significantly higher (25%) than in the Japanese group (3.57%) (P < 0.05). The incidence of abnormal insertion of the cord was significantly higher (14.2%) in the Japanese group than in the Himalayan group (5%) (P < 0.05). There was no significant difference in the frequencies of intervillous thrombosis and infarction between the two groups. These findings suggest that the incidence of pathological change such as chorangiosis and chorangioma may be increased in placentas at Himalayan altitudes.

The expression of the placental anticoagulant protein, annexin V, by villous trophoblasts: Immunolocalization and in vitro regulation

We evaluated the histological and ultrastructural localization of the potent anticoagulant protein, annexin V, at the light and electron microscopic levels, using immunohistochemistry and an immunogold method. Annexin V was found to localize to the microvillar surface of the villous syncytiotrophoblasts. Isolated villous-derived trophoblasts were then utilized to evaluate the expression of annexin 1 protein mRNA in response to syncytialization in vitro, as well as to exposure to adenylate cyclase and protein kinase C agonists. Levels of immunoreactive annexin V released into the conditioned media and associated with cell protein were assessed by ELISA while levels of annexin V mRNA were evaluated by Northern analysis. No significant change in either media or cell-associated annexin V concentrations were detected over time in culture or in response to 1.5 mM 8-bromo-cyclic-adenosine-monophosphate (8-b-cAMP) or 0.15 nM phorbol ester myristic acid (PMA). These results indicate that annexin V is ideally positioned to inhibit intervillous thrombosis and maintain the fluidity of the intervillous circulation. Moreover, the absence of trophoblast annexin V regulation by intracellular second messenger regulators suggests that this crucial placental anticoagulant factor is constitutively produced.

The immunobiology and obstetrical consequences of antiphospholipid antibodies.

Two classes of antiphospholipid antibodies (APA) are associated with adverse pregnancy outcomes. Those APA identified by immunoassays using phospholipid-coated surfaces (e.g., anticardiolipin antibodies) seem to bind to the 57 kD anticoagulant protein, beta 2-glycoprotein-I, when complexed with anionic phospholipid bilayers. Such APA may or may not prolong phospholipid-dependent clotting assays. A second class of APA are identified by their interference with phospholipid-dependent clotting assays (i.e., lupus anticoagulants). The latter bind to phospholipids present in a unique hexagonal phase either alone or complexed with prothrombin or beta 2-glycoprotein-I. There is evidence that both classes of APA are directly responsible for adverse pregnancy outcomes including spontaneous abortions, stillbirths, fetal growth retardation, thrombosis, thrombocytopenia, and preeclampsia. Putative APA-mediated pathogenic mechanisms include intervillous thrombosis, intravillous infarctions and decidual vasculopathy. The thrombogenicity of APA may result from their interference with endothelial phospholipids required for antithrombin III and protein C and S anticoagulant activity and prostacyclin synthesis and/or increased endothelial expression of the procoagulants: tissue factor, von Willebrand factor, platelet-activating factor, and plasminogen activator inhibitor type-1. Other prothrombotic properties seem to include: increased platelet aggregation, and reduced beta 2-glycoprotein-1 and annexin V anticoagulant activity. Rigorous diagnostic criteria must be applied to the detection of both classes of APA because the prevention of adverse pregnancy outcomes requires potentially hazardous anticoagulant therapy.

A clinico-pathologic evaluation of intervillous thrombosis

A clinico-pathologic evaluation of intervillous thrombosis

Ultrasonographic diagnosis of a large placental intervillous thrombosis associated with elevated maternal serum α-fetoprotein level

A placental lesion associated with elevated maternal serum «-fetoprotein level and a positive Kleihauer-Betke test is reported. Serial ultrasonograms showed a progressive increase in the echogenicity of the lesion that corresponded to a large intervillous thrombosis after delivery. This case illustrates the importance of detailed ultrasonographic and pathologic placental investigations in pregnancies with unexplained elevated levels of a-fetoprotein. (Am J Obstet Gynecol 1990;163:1558-60.)

Placental hypoechoic-anechoic areas and infarction: sonographic-pathologic correlation.

High-resolution ultrasound (US) and pathologic analysis were used to define the relationship between placental hypoechoic-anechoic areas, frequently seen in the third trimester, and the clinically significant entity of placental infarction. Placentas were obtained from three groups of patients: those prospectively demonstrating one or more placental hypoechoic-anechoic areas greater than or equal to 1 cm in diameter on third-trimester sonograms (n = 14), those with risk factors for vascular disease (n = 12), and control patients without risk factors (n = 16). Pathologic analysis demonstrated significantly more infarcts in patients with risk factors than in control patients (17 vs three, P = .047). Of a total of 22 infarcts from all three groups, 19 (86%) were isoechoic to viable placenta and therefore not detected with US. The three infarcts identified with US contained hypoechoic or anechoic foci of fibrin or hemorrhage. Of 26 placental hypoechoic-anechoic areas 23 (88%) were decidual septal cysts or intervillous thrombosis without infarction. The authors conclude that nonhemorrhagic placental infarction cannot be identified with ex utero US and, by inference, that prenatal US is probably insensitive for detection of placental infarction.

Placental Less and Maternal Hemoglobin Levels: A Comparative Investigation

A high maternal hemoglobin level during pregnancy has been correlated to a low birth weight and a low placental weight, but has not been investigated in relation to placental factors. In 330 consecutive deliveries, placental lesions, birth weight and placental weight were studied in a multiple regression analysis in relation to maternal hemoglobin concentration, taking into consideration possible confounding factors such as smoking, hypertensive disorders, weight gain, primiparity, gestational age and sex. A high maternal hemoglobin concentration (greater than 130 g/l) was correlated with a low birth weight, acute infarcts and syncytial knots. Intervillous thrombosis was more common in non-smokers and multiparous women, increasing in incidence as gestational age advanced. Infarcts and microscopic perivillous fibrin were correlated with hypertension. Microscopic perivillous fibrin was slightly associated with a high hemoglobin level (greater than 130 g/l) in a bivariate analysis. These findings may indicate that a high maternal hemoglobin level impairs the uteroplacental circulation.