Twin Anemia-polycythemia Sequence Placentas Research Articles

Increased placental expression of angiotensin-converting enzyme 2, the receptor of SARS-CoV-2, associated with hypoxia in twin anemia-polycythemia sequence (TAPS)

IntroductionRecent reports suggest SARS-CoV-2, the virus causing COVID-19, may be transmittable from pregnant mother to placenta and fetus, albeit rarely. The efficacy of vertical transmission of SARS-CoV-2 critically depends on the availability of its receptor, ACE2, in the placenta. In the present study, we tested the hypothesis that placental ACE2 expression is oxygenation-dependent by studying the expression of ACE2 and associated cell entry regulators in the monochorionic twin anemia-polycythemia (TAPS) placenta, a model of discordant placental oxygenation. MethodsWe performed a retrospective comparative immunohistochemical, immunofluorescence and Western blot analysis of ACE2, TMPRSS2 and Cathepsin B expression in anemic and polycythemic territories of TAPS placentas (N = 14). ResultsACE2 protein levels were significantly higher in the anemic twin territories than in the corresponding polycythemic territories, associated with upregulation of the key ACE2-related cell entry regulators, TMPRSS2 and Cathepsin B, immunolocalized to villous trophoblastic and stromal cells. Cellular colocalization of ACE2 and TMPRSS2, suggestive of functionality of this cell entry axis, was demonstrated by double immunofluorescence studies. DiscussionPlacental hypoxia is associated with upregulation of ACE2 expression, concomitant with increased expression of its key cell entry proteases. ACE2-regulated placental functions, both infection- and non-infection related, may be highly oxygenation-dependent.

Longer distance between umbilical cord insertions is associated with spontaneous twin anemia polycythemia sequence.

The aim of the study was to investigate the placental characteristics in spontaneous twin anemia polycythemia sequence. A retrospective case-control study of spontaneous twin anemia polycythemia sequence, twin-to-twin transfusion syndrome and normal monochorionic diamniotic twin pregnancies was performed. The primary outcome was placental characteristics. The prevalence of artery-artery anastomoses in spontaneous twin anemia polycythemia sequence and twin-to-twin transfusion syndrome groups was significantly lower than in the normal monochorionic diamniotic twin group (40.0% vs 33.3% vs 88.8%, respectively, P<.001). The total number of vascular anastomoses in the spontaneous twin anemia polycythemia sequence group (with range given in parentheses) was significantly lower than in the two control groups (3 [1-6] vs 5 [1-14] vs 6 [1-20], P=.001/<.001/.794). The number of artery-vein anastomoses in the spontaneous twin anemia polycythemia sequence was significantly lower than in the two control groups (2 [1-5] vs 4 [1-13] vs 5 [1-19], P=.011/.001/1.000). The total diameter of all vascular anastomoses was significantly smaller in the spontaneous twin anemia polycythemia sequence than in the two control groups (0.9mm [0.3-4.7] vs 5.2mm [0.8-24.6] vs 7.3mm [1.0-25.1], P<.001/<.001/.104), as was the total diameter of artery-to-artery anastomoses (0.5mm [0.3-1.3] vs 2.0mm [0.5-11.8] vs 2.3mm [0.7-9.7], P=.003/<.001/1.000) and the total diameter of artery-to-vein anastomoses (0.8mm [0.3-2.1] vs 4.6mm [0.8-15.3] vs 4.0mm [0.2-21.8], P<.001/<.001/1.000). The ratio between the distance of the two umbilical cords insertion points and the placental maximum diameter in the spontaneous twin anemia polycythemia sequence group was significantly larger than in the two control groups (0.78 [0.49-0.99] vs 0.64 [0.32-1.00] vs 0.55 [0.05-1.00], P=.033/<.001/.138). In spontaneous twin anemia polycythemia sequence placentas, the number of superficial vascular anastomoses is lower, their diameter is smaller and the distance between the two umbilical cord insertion points is longer.

Evaluation of Color Difference in Placenta with Twin Anemia Polycythemia Sequence.

Twin anemia polycythemia sequence (TAPS) occurs in 5% of monochorionic twins and is characterized by large inter-twin hemoglobin differences. The postnatal diagnostic criteria for TAPS are based on hematologic parameters and placental characteristics. Placental examination after birth shows that color of the maternal side between placental territories of the anemic and polycythemic twins is remarkably different. The color difference in TAPS placentas is higher compared to monochorionic placentas with acute peripartum feto-fetal transfusion; thus, this is used as an additional diagnostic criterion for TAPS. Software such as ImageJ enables the computer-based measurement of color intensity in TAPS placentas. However, a detailed method for the calculation of color differences between anemic and polycythemic components of TAPS placentas has not yet been described. The protocol presented here provides a step-by-step method for analyzing color differences in the maternal side of TAPS placentas using ImageJ software.

Discordant placental oxygenation and autophagy in twin anemia-polycythemia sequence (TAPS)

Background(Macro)autophagy is an important process of self-degradation of macromolecules and organelles that ensures cellular homeostasis and energy preservation during stressful conditions. Dysregulated placental autophagy has been implicated in a wide range of pregnancy complications. Recent studies identified hypoxia as a key regulator of trophoblast autophagy in vitro; however, its effects on placental autophagy in vivo remain incompletely understood. In this study, we evaluated the monochorionic twin anemia-polycythemia sequence (TAPS) placenta as model of discordant placental oxygenation to determine the effects of hypoxia on placental autophagy in utero. MethodsWe performed a retrospective comparative analysis of tissue oxygenation and autophagy in anemic and polycythemic territories of TAPS placentas (N = 12). Archival tissues were subjected to immunohistochemical, immunofluorescence and Western blot analyses of carbonic anhydrase (CA) IX (hypoxia marker) and key autophagy/lysosomal markers. ResultsCAIX protein levels were significantly higher in anemic twin territories than in corresponding polycythemic territories, consistent with relative tissue hypoxia. Anemic placental shares further displayed significantly higher levels of LC3I/II (autophagosome markers) and LAMP1/2 (lysosome markers), associated with upregulated expression of lysosome/autophagosome activity-associated markers, transcription factor EB and cathepsin D. The accumulation of autophagosomes and lysosomes in anemic shares was accompanied by elevated p62 protein expression, suggestive of inhibition of the downstream autophagy pathway. ConclusionsTAPS placentas display striking intertwin discordance in tissue oxygenation and autophagic activity and may provide a suitable model for study of the interrelationship between hypoxia, autophagy, and pregnancy outcome in a monochorionic twin setting.

Can color difference on the maternal side of the placenta distinguish between acute peripartum twin–twin transfusion syndrome and twin anemia–polycythemia sequence?

ObjectiveTo investigate the color difference between two placental shares in monochorionic placentas with acute peripartum twin–twin transfusion syndrome (TTTS) and twin anemia–polycythemia sequence (TAPS). MethodsWe evaluated all digital pictures of TAPS, acute peripartum TTTS and a control group of uncomplicated monochorionic placentas examined at our center. We determined the color intensity of the individual placental share on the maternal side of each monochorionic placenta using an image–processing program and calculated the color difference ratio (CDR). ResultsDigital pictures of 5 acute peripartum TTTS, 25 TAPS and 54 control group placentas were included in this study. The median CDR in acute peripartum TTTS was significantly lower compared to TAPS placentas, 1.20 (inter-quartile range (IQR) 1.05–1.20) and 2.50 (IQR 1.85–3.34), respectively (p < 0.01), and was comparable to the control group (CDR 1.11, IQR 1.05–1.22). ConclusionTAPS placentas have a higher CDR compared to acute peripartum TTTS placentas. Examining color difference on the maternal side of the placenta might help distinguish between acute peripartum TTTS and TAPS.

Injection des anastomoses vasculaires pour la compréhension des complications propres aux grossesses monochoriales

ObjectivesThe aim of the study is to compare placental monochorionic angioarchitecture complicated with twin-oligohydramnios-polyhydramnios sequence (TOPS), twin anemia polycythemia sequence (TAPS), twin reversed arterial perfusion (TRAP) and selective intra uterine growth restriction (sIUGR) to normal uneventful monochorionic placenta. MethodsBetween December 2012 and December 2015, monochorionic placenta has been studied at the multiple pregnancy care center of the Femme-Mère-Enfant Hospital in Lyon. Umbilical chords were catheterized and dye injected for macroscopic analysis of angioarchitecture at the anatomopathology department. Placentas treated with laser foetoscopic surgery were excluded. ResultsA total of 126 placentas were injected in the post-partum period. In total, 95% (119/126) of the placentas presented arteriovenous anastomoses (AVA). Median number of AVA was 7. The prevalence of at least one velamentous cord insertion was higher in TOPS and selective intrauterine growth restrictions P<0.01 and P<0.01 respectively, compared to uneventful pregnancies. Arterio-arterial anastomoses (AAA) were present in 82.7% (77/93) of uneventful placentas versus 33.3% of TOPS (P<0.01) and 28.5% of TAPS (P<0.01). The prevalence of veno-venous anastomoses was significantly higher in TOPS (P<0.01). All TAPS placentas showed marginal arteriovenous anastomoses. In TRAP placenta, the acardiac twin had no specific vascular territory. ConclusionThe study confirms literature findings on prevalence of vascular anastomoses in monochorial placentas, suggesting the protective role of AAA in TOPS and TAPS. The role of VVA is yet hard to determinate. Macroscopic observations of monochorionic placentas are valuable and essential keys for understanding, managing and treating anastomotic syndromes.

The Placenta in Twin-to-Twin Transfusion Syndrome and Twin Anemia Polycythemia Sequence.

Twin-to-twin transfusion syndrome (TTTS) and twin anemia polycythemia sequence (TAPS) are complications unique to monochorionic twin pregnancies and their shared circulation. Both are the result of the transfusion imbalance in the intertwin circulation. TTTS is characterized by an amniotic fluid discordance, whereas in TAPS, there is a severe discordance in hemoglobin levels. The article gives an overview of the typical features of TTTS and TAPS placentas.

Color Difference in Placentas with Twin Anemia-Polycythemia Sequence: An Additional Diagnostic Criterion?

Objective: To determine the color intensity difference between the 2 placental shares in monochorionic placentas with twin anemia-polycythemia sequence (TAPS). Methods: We evaluated all digital pictures of TAPS placentas examined at our center and compared them to a control group of uncomplicated monochorionic placentas. We determined the color intensity of individual placental share on the maternal side of each monochorionic placenta using an image processing program and calculated the color difference ratio (CDR). Results: Digital pictures of 19 TAPS and 19 uncomplicated monochorionic placentas were included in this study. The TAPS group consisted of 12 spontaneous TAPS placentas (63%) and 7 post-laser TAPS placentas (37%). The median CDR in the group with TAPS was significantly higher than in the control group, 2.73 (range 1.73-6.36) versus 1.09 (range 1.00-1.35), respectively (p < 0.01). We found a positive correlation between CDR and inter-twin hemoglobin (Hb) difference in the TAPS group (R = 0.66, p < 0.01) but not in the control group (R = 0.04, p = 0.87). Conclusion: TAPS placentas have a significantly higher CDR compared to uncomplicated monochorionic twin placentas. Large inter-twin Hb differences in TAPS are associated with higher CDR.

EP07.03: Variability of the clinical course of monochorionic twins based on a different architecture of placental bed

There are known complications of monochorionic twins: the TTTS (Twin–twin transfusion syndrome), sIUGR (selective intrauterine growth restriction), TAPS (twin anemia polycythemia sequence), TRAP (twin reversed arterial perfusion). The most frequent cases are TTTS, sIUGR and their combinations. The study is based on detailed analysis of the placental vessels and correlated with known clinical course. Therefore the prediction <span style = ''line-height:20.7999992370605px''> of clinical courses of monochorionic twins by ultrasound techniques. We analysed 65 monochorionic biamniotic placentas by use of histological colours. The history of clinical course was known in all cases including ultrasound measurements. Cases of placentas which were not applicable for analysis or cases with unknown clinical courses were excluded. We defined 5 most frequent types of clinical courses of monochorionic twins. The type I – clear TTTS, type II – clear sUIGR, type III – flow type III of sIUGR, type IV and V – combination of TTTS and sIUGR depending on the way of transfusion. TRAP and TAPS placentas were also defined. The knowledge of placental vascular architecture together with known clinical course of monochorionic twins is useful tool for the next management and approach.

Pre-Operative Twin Anemia/Polycythemia in the Setting of Twin-Twin Transfusion Syndrome (TTTS)

Introduction: Twin-twin transfusion syndrome (TTTS) and twin anemia-polycythemia sequence (TAPS) are classified as distinct clinical disorders associated with unbalanced blood flow through placental vascular communications. Typically, TAPS placentas demonstrate few <1 mm arteriovenous (AV) communications, and at fetoscopy the twins are visibly pale and plethoric. Materials and Methods: In a cohort of TTTS patients who underwent laser surgery, those with preoperative findings suggestive of anemia/polycythemia (AP) were compared to those with TTTS alone. AP was defined as middle cerebral artery peak systolic velocity in one twin >1.5 multiples of the median (MoM), and <1.0 MoM in the other. Results: Of 369 TTTS patients, 9 (2.4%) met criteria for preoperative AP. The mean number (±SD) of AV communications in the TTTS + AP group was 5.6 ± 5.7, compared with 8.8 ± 4.8 in the TTTS-alone group (p = 0.013). Five TTTS + AP patients (56%) had a few thin AV communications (mean 2.8 ± 1.6); all 5 had visibly pale and plethoric twins. The remaining 4 (44%) had large or numerous anastomoses (mean 10.5 ± 6.8); none had fetal skin color discordance. Discussion: Preoperative AP affected 2% of TTTS patients. Of these, approximately half had placental and skin color findings typically reported with isolated TAPS.

Prevalence, size, number and localization of vascular anastomoses in monochorionic placentas

IntroductionMost monochorionic (MC) twin pregnancies have an uncomplicated course, but some develop severe complications including selective intrauterine growth restriction (sIUGR), twintwin transfusion syndrome (TTTS) and twin anemia–polycythemia sequence (TAPS). The underlying pathogenesis of these various complications is associated with the ubiquitous presence of vascular anastomoses in MC placentas. MethodsThe aim of this study was to estimate the prevalence, number, size and localization of the anastomoses in sIUGR, TTTS and TAPS placentas compared to normal MC placentas using color dye injection. We excluded MC twin pregnancies treated with fetoscopic laser surgery or selective feticide. ResultsA total of 235 placentas fulfilled the inclusion criteria: 126 normal MC, 47 TTTS, 46 sIUGR and 16 spontaneous TAPS. Median number of anastomoses in normal MC, sIUGR, TTTS and TAPS placentas was 8 (IQR: 4–12), 8 (IQR: 5–14), 7 (IQR: 5–11) and 4 (IQR: 3–5), respectively. The prevalence of arterio-arterial (AA) anastomoses in normal MC, sIUGR, TTTS and TAPS placentas was 96%, 98%, 47% and 19%, respectively. We found AV anastomoses to be evenly distributed along the vascular equator in all MC placentas except in TAPS cases, where anastomoses were mostly localized near the margin. We also found that, in sIUGR and TTTS placentas, AA anastomoses tended to be at the center of the placenta. ConclusionThe present study shows that the prevalence, size, number and localization of the various types of anastomoses differ between normal MC, sIUGR, TTTS and TAPS placentas.

Arterio-arterial vascular anastomoses in monochorionic twin placentas with and without twin anemia-polycythemia sequence

We performed a matched case–control study to analyze the placental angioarchitecture, in particular the diameter of arterio-arterial (AA) anastomoses in monochorionic placentas from pregnancies with spontaneous twin anemia-polycythemia sequence (TAPS) compared to a control group of uncomplicated monochorionic placentas. Placental angioarchitecture was analyzed using colored dye injection. AA anastomoses were detected in 20% (3/15) of spontaneous TAPS placentas. The median diameter of AA anastomoses in the group with and without TAPS was 0.4 mm and 2.2 mm, respectively (p = 0.01). In conclusion, AA anastomoses are rarely detected in TAPS placentas. When present, the AA anastomosis is very small, preventing equilibration of hemoglobin levels between both twins.

Placental Characteristics in Monochorionic Twins With and Without Twin Anemia–Polycythemia Sequence

To study the placental angioarchitecture of monochorionic placentas with and without twin anemia-polycythemia sequence. Eligible were all placentas from monochorionic twin gestations, not complicated by twin-to-twin transfusion syndrome and resulting in double survival. The study was conducted at two European Fetal Therapy Centers between 2002 and 2008. Placental angioarchitecture was evaluated using colored dye injection. Diagnosis of twin anemia-polycythemia sequence was based on the presence of large intertwin hemoglobin difference without the degree of amniotic fluid discordance that is required for the diagnosis of twin transfusion syndrome. Three-hundred thirteen monochorionic twin pregnancies were eligible for the study but placental data could not be completed for 62 placentas (20%). This left 251 monochorionic twin pregnancies of which 11 (4%) fulfilled the criteria for twin anemia-polycythemia sequence. The median number of anastomoses in monochorionic placentas with and without twin anemia-polycythemia sequence was 3 (range: 2-5) and 7 (range: 0-25), respectively (P<.001). Small anastomoses were present in 91% (10/11) of twin anemia-polycythemia sequence-placentas compared with 5% (12/240) of cases without twin anemia-polycythemia sequence (P<.001). Arterioarterial anastomoses were absent in twin anemia-polycythemia sequence-placentas and present in 89% (213/240) of placentas without twin anemia-polycythemia sequence (P<.001). Monochorionic twin placentas with twin anemia-polycythemia sequence are characterized by a paucity of anastomoses and the absence of arterioarterial anastomoses. The few anastomoses that are present in twin anemia-polycythemia sequence placentas are mostly small arteriovenous anastomoses.

Pancreatic transplantation or intensive insulin therapy?

Twin anemia-polycythemia sequence (TAPS) may occur in monochorionic twins either spontaneously or after laser surgery for twin–twin transfusion syndrome. Our aim was to analyze the placental angioarchitecture in spontaneous versus post-laser TAPS.We included all monochorionic twin placentas with spontaneous or post-laser TAPS injected at our center between 2002 and 2012. Placental angioarchitecture was evaluated using colored dye injection.A total of 600 monochorionic placentas were injected during the study period of which 43 (7.2%) with TAPS (spontaneous TAPS, n = 16; post-laser TAPS, n = 27). Almost all anastomoses (96%; 119/124) were very small (diameter <1 mm) and the majority was localized near the placental margin. The median number of anastomoses per placenta was 4 (interquartile range (IQR): 3–5) in the spontaneous TAPS group and 2 (IQR: 1–3) in the post-laser TAPS group (p = 0.003). Arterio-arterial (AA) anastomoses were detected in 14.0% (6/43) of TAPS placentas and were all minuscule (diameter <1 mm). The rate of AA anastomoses in the spontaneous TAPS group and post-laser TAPS group was 18.8% (3/16) and 11.1% (3/27), respectively (p = 0.184).Spontaneous TAPS placentas have a significantly higher total number of anastomoses compared to post-laser TAPS placentas. Most anastomoses were localized near the margins of the placenta. Minuscule AA anastomoses were detected sporadically in both groups and the rate of AA anastomoses is slightly higher in the spontaneous TAPS group than in the post-laser group.Spontaneous TAPS placentas have a different placental angioarchitecture than post-laser TAPS placentas in terms of number and type of vascular anastomoses.