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Assessment of Feto-fetal Transfusion Flow Through Placental Arterio-venous Anastomoses in a Unique Case of Twin-to-Twin Transfusion Syndrome
Abstract
In vivo measurements of blood flow through arterio-venous anastomoses in monochorionic twin placentas have recently been attempted with Doppler ultrasound, but the accuracy is questionable. We present a case of twin-to-twin transfusion syndrome treated with fetoscopic laser surgery. The ex-recipient subsequently became severely anaemic and was treated with an intrauterine blood transfusion at 29 weeks' gestation. After birth, a placental injection study identified residual unidirectional arterio-venous anastomoses from the ex-recipient to the ex-donor without arterio-venous anastomoses in the opposite direction. Prospective measurements of decreasing haemoglobin levels between the intrauterine transfusion and birth allowed us to assess the net blood flow through the anastomoses as 27.9mL/24h. This finding may also explain the inaccuracy of Doppler flow measurements, as such low flow velocities cannot possibly be detected with current Doppler techniques.
... 6,7 Both spontaneous and post-laser surgery TAPS have a similar anatomic substrate that is based on the presence of only few minuscule arteriovenous placental vascular anastomoses, in the absence of superficial arterioarterial anastomoses. 2,8,9 These few minuscule arteriovenous anastomoses lead to a slow, chronic intertwin blood transfusion 2,9 that allows more time for hemodynamic compensatory mechanisms and may prevent dysregulation of hormonal systems and the development of TOPS. 10 TAPS can be diagnosed antenatally with predefined Doppler-ultrasound criteria 4 or postnatally with hematologic criteria in combination with placental injection studies. 6 Postnatal diagnosis of TAPS is based on the presence of chronic anemia (with highly increased reticulocyte count) in the donor and polycythemia in the recipient in association with typical placental angioarchitecture after injection with colored dye. ...
... To date, outcome in TAPS is based on few case reports. 2,9,14 We hypothesized that neonatal morbidity TAPS cases with double survivors is limited mainly to shortterm hematologic complications without other severe complications. The aim of this study was to determine the neonatal outcome in a large series of neonates with TAPS in comparison with a control group of monochorionic twins without TAPS. ...
... 8 Two spontaneous TAPS cases 2 and 2 post-laser surgery TAPS cases were published previously. 3,9 Each twin pair with TAPS was compared with 2 control monochorionic twin pairs who were unaffected by TAPS or TTTS and matched by gestational age at birth (Ϯ 1 week gestation). ...
The purpose of this study was to evaluate neonatal outcome of monochorionic twin pregnancies complicated by twin anemia-polycythemia sequence (TAPS).
A cohort of consecutive monochorionic twins with TAPS with double survivors was included in the study. Each twin pair with TAPS was compared with 2 monochorionic twin pairs who were unaffected by TAPS or twin-to-twin transfusion syndrome and who were matched for gestational age at birth. Neonatal death, severe morbidity, and cerebral injury were studied.
We included 19 twin pairs in the TAPS group and 38 control twin pairs. The incidence of neonatal death and severe neonatal morbidity was similar in the TAPS group and control group (3% [1/38] vs 1% [1/76] and 24% [9/38] vs 28% [21/76], respectively). Severe cerebral injury was detected in 1 infant (5%) in the TAPS group and 1 infant (2%) in the control group.
Neonatal mortality and morbidity rates in a select population of TAPS neonates are similar to control neonatal rates.
... In 2007, we described a case of post-laser TAPS which occurred despite the presence of a small AA anastomosis. Recently, we also detected an AA anastomosis in a spontaneous TAPS case (case presented at the Eurofoetus meeting, Barcelona, May 2009) [25] . In a series of 20 TAPS placentas injected at our center to date, we detected an AA anastomosis in only the 2 abovementioned cases (incidence of AA anastomoses in TAPS: 10 % ). ...
... In two recent postlaser TAPS cases treated with intrauterine transfusions, we were able to calculate the actual blood fl ow through these small AV anastomoses. We found the anastomotic blood fl ow to be approximately 5 -15 ml / 24 h [7,25] . It is not clear why the donor twin in TAPS case does not develop oligohydramnios and the recipient twin does not develop polyhydramnios. ...
... Up to 33 % of placentas treated with laser may still have residual anastomoses [29] . Residual anastomoses can lead to recurrent TTTS or TAPS [25] . An alternative laser surgery technique (so-called " Solomon " technique) may help reduce the risk of missing a small anastomosis during surgery. ...
Monochorionic twins share a single placenta with inter-twin vascular anastomoses, allowing the transfer of blood from one fetus to the other and vice versa. These anastomoses are the essential anatomical substrate for the development of severe complications, including twin-twin transfusion syndrome (TTTS) and twin-anemia-polycythemia sequence (TAPS). TTTS and TAPS are both chronic forms of feto-fetal transfusion. TTTS is characterized by the twin oligo-polyhydramnios sequence (TOPS), whereas TAPS is characterized by large inter-twin hemoglobin differences in the absence of amniotic fluid discordances. TAPS may occur spontaneously in a minority of monochorionic twins or in TTTS cases after laser treatment. This review focuses on the differences between TAPS and TTTS in terms of pathogenesis, incidence, diagnostic criteria, treatment modalities, perinatal outcome and long-term outcome.
... Placental vascular anastomoses in monochorionic twin gestations may lead to twin-to-twin transfusion syndrome (TTTS). Recently, a variant of TTTS was described: twin anemia-polycythemia sequence (TAPS) [1][2][3]. TAPS is characterized by the presence of a large inter-twin difference in haemoglobin level and reticulocyte count without any signs of the oligo-polyhydramios sequence as seen in TTTS. TAPS may occur spontaneously (spontaneous form) or after laser surgery in the treatment of TTTS (postlaser form). ...
... In a recent report, we described a post-laser case of TAPS in which a residual AA anastomosis was also detected [1]. The current case is the first described case of spontaneous TAPS in the presence of an AA anastomosis. ...
... In contrast with the previously reported case [1], filling of the AA anastomosis with colored dye in the current case occurred easily without increased injection pressure or forced manual compression of the colored dye, suggesting that the AA anastomosis was also patent in utero. Interestingly, the diameter of the AA anastomosis in both cases was very small (<1 mm). ...
Monochorionic twin pregnancies are associated with increased perinatal morbidity and mortality. The vascular placental anastomoses in these pregnancies can cause severe complications. We describe a case of twin anemia-polycythemia sequence (TAPS) with an atypical placental angioarchitecture. During pregnancy serial ultrasound examinations of both twins revealed no amniotic fluid discordance and no abnormal Doppler ultrasound measurements (umbilical cord pulsatility index and middle cerebral artery peak systolic velocity). The twins, born at 33 + 3 weeks gestation after spontaneous onset of labour, were found to be anemic and polycythemic, respectively. Placental examination with colored dye injection showed, apart from small ateriovenous anastomoses, an arterio-arterial anastomosis. As arterio-arterial anastomoses have not been described in cases with spontaneous TAPS to date, it was postulated that such anastomoses carried a protective effect against the development of this complication.
... T win anemia-polycythemia sequence is a rare form of feto-fetal transfusion which may occur in apparently uncomplicated monochorionic twin pregnancies (spontaneous form) or after laser surgery as a treatment for chronic twin-twin transfusion syndrome (iatrogenic form). 1,2 Both forms are characterized by the presence of large intertwin hemoglobin difference without signs of twin oligo-polyhydramnios sequence as seen in the typical form of twin transfusion syndrome. 1,2 Postnatal diagnosis is based on the presence of chronic anemia (with reticulocytosis) in the donor and polycythemia in the recipient. ...
... 1,2 Both forms are characterized by the presence of large intertwin hemoglobin difference without signs of twin oligo-polyhydramnios sequence as seen in the typical form of twin transfusion syndrome. 1,2 Postnatal diagnosis is based on the presence of chronic anemia (with reticulocytosis) in the donor and polycythemia in the recipient. 2,3 Iatrogenic twin anemia-polycythemia sequence has been diagnosed antenatally, using Doppler ultrasonography. ...
... The angioarchitectural basis for twin anemia-polycythemia sequence seems to be small unidirectional arteriovenous anastomoses. 1,2,5 Our knowledge is, however, based on the placental characteristics of a few individual cases. 1,2,5 The aim of the present study was to estimate whether there is a difference in placental angioarchitecture in the placentas of a larger cohort of 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.
... Deep-hidden anastomoses were identified in 58% (7/12). In one case of missed chorionic-plate anastomoses after laser (case 3), a severe unidirectional transfusion developed from the recipient to the donor, necessitating intrauterine transfusion of the anemic twin, as described previously (Lopriore et al., 2006b). One example of a lasered placenta in which multiple deep-hidden anastomoses were identified after casting is shown in Figure 1. ...
... To assess the possible hemodynamic consequences of deep-hidden anastomoses, we estimated the fetofetal transfusion of an observed 0.05-mm diameter vessel connecting adjacent cotyledons. Using electrical network analysis and comparison with a previous clinical case with known fetofetal transfusion (Lopriore et al., 2006b), it was indicated that the flow through this deephidden anastomosis must have been on the order of 0.6-1 mL/24 h (see appendix). In contrast, in the clinical case in which AV fetofetal transfusion caused a significant Hb discordance within 48 h of an intrauterine blood transfusion to treat anemia, the fetofetal transfusion was on the order of 27.9 mL/24 h (Lopriore et al., 2006b) at 29 weeks. ...
... Using electrical network analysis and comparison with a previous clinical case with known fetofetal transfusion (Lopriore et al., 2006b), it was indicated that the flow through this deephidden anastomosis must have been on the order of 0.6-1 mL/24 h (see appendix). In contrast, in the clinical case in which AV fetofetal transfusion caused a significant Hb discordance within 48 h of an intrauterine blood transfusion to treat anemia, the fetofetal transfusion was on the order of 27.9 mL/24 h (Lopriore et al., 2006b) at 29 weeks. In our case, however, gestational age was 37 weeks, suggesting that the deephidden anastomotic fetofetal transfusion at 29 weeks was even lower, estimated between about 0.23 and 0.38 mL/24 h (i.e. ...
Our objective was to identify the clinical consequences of deep-hidden anastomoses that occur underneath the placental surface.
Twelve placentae that underwent intrauterine laser ablation of placental anastomoses for twin-twin transfusion syndrome (TTTS) and 14 non-TTTS controls were investigated for deep-hidden anastomoses. Additionally, we investigated the inter-twin haemoglobin differences as an indicator for fetofetal transfusion. Placentae were divided into four groups: TTTS placentae without residual chorionic-plate anastomoses without deep-hidden anastomoses (group 1) and with deep-hidden anastomoses (group 2), and non-TTTS placentae with chorionic-plate anastomoses without deep-hidden anastomoses (group 3) and with deep-hidden anastomoses (group 4).
Deep-hidden anastomoses were identified in 58% (7/12) of the TTTS placentae after laser surgery and in 64% (9/14) of the non-TTTS placentae. Groups 1 and 2 had equal inter-twin haemoglobin differences: medians 1.4 and 1.2 gr/dL, respectively (p = 0.48). In group 3, the median inter-twin haemoglobin difference without deep-hidden anastomoses was 2.6 gr/dL (group 3) and with deep-hidden anastomoses (group 4) it was 5.1 gr/dL (p = 0.26).
Both comparisons imply that deep-hidden anastomoses did not cause any additional increase in Hb difference. In conclusion, haematological and additional hemodynamical analysis show that deep-hidden anastomoses are likely to occur without any clinical consequences.
... 2 Residual anastomoses may lead to several complications, including persistence of TTTS, reversal of TTTS, and isolated fetal hemoglobin difference, also named twin anemia polycythemia sequence (TAPS). [3][4][5][6] In contrast to TTTS, TAPS is not associated with the characteristic finding of twin oligo-polyhydramnios sequence. TAPS may occur in up to 13% of treated cases and has been shown to result from small unidirectional residual anastomoses. ...
... TAPS may occur in up to 13% of treated cases and has been shown to result from small unidirectional residual anastomoses. [3][4][5][6] Guidelines for the management of TAPS are not available. Therapeutic options for TAPS vary from expectant management to a more aggressive approach such as a second laser procedure, intrauterine transfusion, or selective feticide. ...
... 7 As shown in a TTTS model, another possible explanation for transient fetal hydrops in donor twins after laser is the result of the rapid dilution of the donor blood after amnioreduction following laser. 8 In a recent series of 101 consecutive TTTS cases treated with laser, Robyr et al 4 detected 13 cases of TAPS (13%), [3][4][5][6] often resulting from small unidirectional residual anastomoses. 9 In the present case, TAPS and fetal hydrops in the recipient was also very likely caused by se-vere fetal anemia. ...
We present a case of twin anemia-polycythemia sequence after laser surgery for twin-to-twin transfusion syndrome which resolved spontaneously. No residual anastomoses were identified after placental injection with colored dye. We discuss the possible pathogenetic mechanisms that may have led to this remarkable clinical course and discuss the various management options.
... The ex-recipient became anemic and required an intra-uterine blood transfusion. We measured the total Hb concentration before and after transfusion, and after emergency delivery 2 days later, related the decrease in total Hb to the AV flow and determined it as 28 ml/24 h (Lopriore et al 2007). ...
... Thus, utilizing the time behavior of adult Hb concentrations gives more accurate values of inter-twin transfusions than total, i.e. adult plus fetal Hb concentrations. However, two complicating factors not addressed previously (Lopriore et al 2007) need to be dealt with: first, the finite lifetime of adult red blood cells, which is on the order of tens of days (Brace et al 2000) and, second, multiple intra-uterine transfusions. Therefore, we sought to derive the equations relating net inter-twin transfusions with adult Hb concentrations, neglecting the small production in fetal red blood cells, but accounting for their finite lifetime. ...
... Further, the recipient's blood volume is also included in the equations and we suggest that it follows from the ratio of the birth weights to the donor's measured pre-natal blood volume. Previously (Lopriore et al 2007), we presented the expression for the AV flow related to measured total Hb concentrations, neglecting the production and decay of fetal red blood cells. Although not addressed further in this note, these results will also be summarized in tables 2 and 3. Table 2 summarizes the outcomes of the analysis. ...
Twin-twin transfusion syndrome (TTTS) is a severe complication of monozygotic (identical) twin fetuses sharing one single (monochorionic) placenta. TTTS is caused by a net inter-twin transfusion of blood through placental anastomoses, from one twin (the donor) to the other (the recipient), which link the two feto-placental circulations. Currently, the only reliable method to measure the net inter-twin transfusion clinically is when incomplete laser therapy of TTTS occurs and one of the twins becomes anemic and requires an intra-uterine transfusion of adult red blood cells. Then, differences between adult hemoglobin concentrations measured during the transfusion and at birth relate not only to the net inter-twin transfusion but also to the finite lifetime of the adult red blood cells. We have analyzed this situation, derived the differential equations of adult hemoglobin in the donor and recipient twins, given the solutions and given expressions relating the net inter-twin flow with clinically measured parameters. We have included single and multiple intra-uterine transfusions. In conclusion, because incomplete laser therapy occurs frequently, and some cases require an intra-uterine transfusion, this method may allow collecting a wealth of net inter-twin flow data from clinicians involved in laser therapy of TTTS. To aid to the widespread use of this method, we have presented the equations as clearly as possible in tables for easy use by others.
... We recently described a new form of TTTS: twin anaemiae polycythaemia sequence (TAPS). 45,46 This atypical form of TTTS can occur spontaneously (natural form) or after laser surgery (iatrogenic form). Both forms are characterized by the presence of large intertwin haemoglobin difference without signs of twin oligopolyhydramnios sequence (TOPS) as seen in the typical form of chronic TTTS. ...
... Both forms are characterized by the presence of large intertwin haemoglobin difference without signs of twin oligopolyhydramnios sequence (TOPS) as seen in the typical form of chronic TTTS. 45,46 Interestingly, in iatrogenic TAPS, it is usually the former recipient who becomes anaemic, whereas the former donor becomes polycythaemic. 26,47,48 The iatrogenic form of TAPS after laser occurs in up to 13% of cases; 26 the incidence of the spontaneous form of TAPS is not known. ...
... TAPS appears to be mediated through a few minuscule arteriovenous anastomoses (Fig. 3). 45,46 We recently calculated that the blood flow across such small arteriovenous anastomoses might be as low as 5.6 mL/24 h. 45,46 We hypothesized that if only a few very small vascular anastomoses are present, intertwin blood transfusion might occur very slowly, allowing more time for haemodynamic compensatory mechanisms to take place. ...
Placental vascular anastomoses are almost invariably present in monochorionic (MC) placentas. These anastomoses are the essential anatomical substrate for the development of several haematological complications in MC twins, in particular twin-to-twin transfusion syndrome (TTTS). Several forms of TTTS have been described, including chronic TTTS, acute perimortem TTTS, twin anaemia-polycythaemia sequence, acute perinatal TTTS and twin reversed arterial perfusion sequence. A significant evolution in prenatal care strategies and management options for patients with TTTS has occurred during the last decade. In chronic TTTS, endoscopic laser ablation of communicating placental vessels has led to an increase in survival rates. This review analyzes the possible pathophysiologic mechanisms involved, discusses the latest findings in diagnosis, therapy and prognosis, and focuses on fetal and neonatal haematologic complications associated with the various forms of TTTS.
... The intertwin vascular anastomoses have a key role in the pathogenesis of TTTS and sFGR. In 2007, a new MC pregnancy complication was described by Lopriore et al. [108] that involves a discordance in postnatal hemoglobin and hematocrit levels, a difference in neonate reticulocyte levels, and small AV anastomoses in the placenta after colored dye injection (Figure 9). This condition was named twin anemia polycythemia sequence. ...
... This condition was named twin anemia polycythemia sequence. TAPS happens when blood from one twin is slowly transfused to the other by small AV anastomoses at a 5-15 ml/ 24 h rate [108]. Unlike TTTS, there is a less acute and well-compensated intertwin transfusion process leading to a discordance in hemoglobin levels without hemodynamic or amniotic fluid alterations [110]. ...
... En términos generales, se estima la tasa de mortalidad sin tratamiento en un 80-100 %, con un porcentaje entre 15-50 % de secuelas neurológicas. 4,7,8 Así pues, en los países desarrollados, y gracias a los continuos avances en terapia fetal y diagnóstico prenatal, el pronóstico es bueno si el tratamiento se hace de forma precoz y resulta efectivo. 7,9,10 Sin embargo, en países no desarrollados, el pronóstico es muy desalentador; por lo que son raros los casos de fetos nacidos que presenten buena calidad de vida. ...
... En términos generales, se estima la tasa de mortalidad sin tratamiento en un 80-100 %, con un porcentaje de entre 15-50 % de secuelas neurológicas. 4,7,8,17 Así pues, en los países desarrollados, y gracias a los continuos avances en terapia fetal y diagnóstico prenatal, el pronóstico es bueno si el tratamiento se hace de forma precoz y resulta efectivo. 7,9,10 Sin embargo, en países no desarrollados, el pronóstico es muy desalentador, por lo que son raros los casos de fetos nacidos que presenten buena calidad de vida. ...
Twin-twin transfusion syndrome is one of the most serious complications of monochorionic multiple gestations. Its etiology is due to a chronic blood transfusion from de donor twin to the recipient twin through the vascular anastomoses between the placental territories of both fetuses. The characteristic clinical presentation appears in both donor and recipient fetuses, as a direct consequence of altered volemia in each one. Polyhydramnios related to polyuria resulting from a state of constant hypervolemia is observed in the recipient twin, finally evolving into congestive heart failure. The clinical presentation in the donor twin is reversed and characterized by oligoamnios, oliguria, retarded intrauterine growth and hypovolemia, with untreated mortality rates ranging 80-100 % of all cases, which may vary depending on the severity of the transfusion. The diagnosis is based on exhaustive echographic examination of both fetuses to make an early diagnosis and correct staging, since the prognosis depends very much on early action. The treatment of choice is fetoscopic laser coagulation of vascular anastomoses between 18 and 26 weeks of gestation. The prognosis is variable, depending on the availability of fetal therapy and the gestational age at diagnosis, being prognosis generally very poor without an effective treatment.
... These few small anastomoses shared between the two placentas allow a chronic and slow transfusion of blood from the donor to the recipient twin (Figure 1). The actual blood flow through these small anastomoses ranges from 5 to 15 mL per 24 hours Lopriore, van den Wijngaard et al., 2007). This process gradually leads to highly discordant Hb levels, causing the donor twin to become anemic and the recipient twin to become polycythemic. ...
... AA anastomoses are rare in TAPS cases and occur in 10-20% of TAPS placentas. AA anastomoses are considered to protect against the development of TTTS or TAPS because of the bidirectional blood flow, allowing inter-twin equilibration of blood volumes (de Villiers et al., 2012;Lopriore, van den Wijngaard et al., 2007;Suzuki, 2010;van Meir et al., 2010).The size of AA-anastomoses in TAPS appear to be significantly smaller (diameter <1 mm) compared to AA anastomoses in TTTS cases or in uncomplicated monochorionic twins (Zhao et al., 2013). Spontaneous TAPS placentas differ from post-laser TAPS placentas. ...
Monochorionic twins share a single placenta and are connected with each other through vascular anastomoses. Unbalanced inter-twin blood transfusion may lead to various complications, including twin-to-twin transfusion syndrome (TTTS) and twin anemia polycythemia sequence (TAPS). TAPS was first described less than a decade ago, and the pathogenesis of TAPS results from slow blood transfusion from donor to recipient through a few minuscule vascular anastomoses. This gradually leads to anemia in the donor and polycythemia in the recipient, in the absence of twin oligo-polyhydramnios sequence (TOPS). TAPS may occur spontaneously in 3–5% of monochorionic twins or after laser surgery for TTTS. The prevalence of post-laser TAPS varies from 2% to 16% of TTTS cases, depending on the rate of residual anastomoses. Pre-natal diagnosis of TAPS is currently based on discordant measurements of the middle cerebral artery peak systolic velocity (MCA-PSV; >1.5 multiples of the median [MoM] in donors and <1.0 in recipients). Post-natal diagnosis is based on large inter-twin hemoglobin (Hb) difference (>8 g/dL), and at least one of the following: reticulocyte count ratio >1.7 or minuscule placental anastomoses. Management includes expectant management, and intra-uterine blood transfusion (IUT) with or without partial exchange transfusion (PET) or fetoscopic laser surgery. Post-laser TAPS can be prevented by using the Solomon laser surgery technique. Short-term neonatal outcome ranges from isolated inter-twin Hb differences to severe neonatal morbidity and neonatal death. Long-term neonatal outcome in post-laser TAPS is comparable with long-term outcome after treated TTTS. This review summarizes the current knowledge after 10 years of research on the pathogenesis, diagnosis, management, and outcome in TAPS.
... In addition, this study confirms that only a minority of TAPS placentas (20%) contains an AA anastomosis [1], a significantly lower incidence compared to uncomplicated MC pregnancies (89%) [2]. Although the presence of an AA anastomosis may have an important protective effect, it does not preclude the development of TAPS [3,4,6]. ...
... As previously shown, the pathogenesis of TAPS seems to be based on a unique angioarchitecture characterized by the presence of a paucity of minuscule vascular anastomoses [2]. The few small anastomoses allow a slow transfusion of blood (as low as 5e15 ml/24h) from the donor to the recipient, leading gradually to highly discordant hemoglobin levels [6,7]. ...
... Severe anemia in the donor twin can lead to fetal hydrops, severe acidemia, and perinatal death while severe polycythemia in the recipient twin can cause impaired perfusion, skin necrosis, vascular limb occlusion and perinatal death [3] . Several management options have been proposed for TAPS, including intrauterine transfusion (IUT), laser surgery, elective delivery and expectant management, but the optimal management is not clear [1,[4][5][6][7] . ...
... The management of TAPS is controversial and includes IUT (intravascular or intraperitoneal), laser surgery, selective feticide, elective delivery and expectant management [3][4][5]7] . Fetoscopic laser surgery is the only causative treatment for TAPS but is technically challenging due to the absence of polyhydramnios and the presence of only minuscule anastomoses. ...
Twin anemia-polycythemia sequence (TAPS) is a rare condition which may occur either spontaneously in uncomplicated monochorionic twin pregnancies or may develop after laser treatment in twin-twin transfusion syndrome. TAPS is characterized by a large intertwin discordance in hemoglobin levels without discordance in amniotic fluid levels, and may lead to severe complications including fetal hydrops, hematological morbidity and perinatal mortality. Several treatments have been proposed including intrauterine transfusion, laser surgery, elective delivery and expectant management. The optimal treatment remains unclear. In this case series we report 3 TAPS cases managed recently at our center with a combination of intrauterine blood transfusion for the anemic twin and intrauterine partial exchange transfusion for the polycythemic twin. In 1 case, the donor was found to have severe cerebral injury on neuroimaging examination. We propose etiologic mechanisms for cerebral injury in TAPS, discuss the rationale behind this treatment alternative, and evaluate the pros and cons of the various management options.
... In contrast to TTTS, which results from imbalanced intertwin blood transfusion in combination with imbalanced hormonal regulation, TAPS probably results mainly from slow intertwin blood transfusion without hormonal imbalance [10] . We have recently been able to calculate the actual blood flow through these small AV anastomoses in two postlaser TAPS cases, and found the anastomotic blood flow to be approximately 5-15 ml/24 h [6,11] . In a recent study on the placental angioarchitecture of 11 consecutive spontaneous TAPS placentas compared to 240 pla-centas from uncomplicated monochorionic twin pregnancies, we found that TAPS placentas were characterized by the presence of only very few and small unidirectional AV anastomoses in the absence of arterioarterial (AA) anastomoses [12] . ...
... Although AA anastomoses are rare in TAPS, the presence of an AA anastomosis does not preclude the development of TAPS. In 2007, we described a case of postlaser TAPS which occurred despite the presence of a small AA anastomosis [11] . Recently, we also detected an AA anastomosis in a spontaneous TAPS case [13] . ...
Monochorionic twins share a single placenta with intertwin vascular anastomoses, allowing the transfer of blood from one fetus to the other and vice versa. These anastomoses are the essential anatomical substrate for the development of several complications, including twin-twin transfusion syndrome (TTTS) and twin anemia-polycythemia sequence (TAPS). TTTS and TAPS are both chronic forms of fetofetal transfusion. TTTS is characterized by the twin oligopolyhydramnios sequence, whereas TAPS is characterized by large intertwin hemoglobin differences in the absence of amniotic fluid discordances. TAPS may occur spontaneously in up to 5% of monochorionic twins and may also develop after incomplete laser treatment in TTTS cases. This review focuses on the pathogenesis, incidence, diagnostic criteria, management options and outcome in TAPS. In addition, we propose a classification system for antenatal and postnatal TAPS.
... In the previous case, published by our group in 2007 [9], the flow that we calculated (28 mL/24 h) was higher compared to the current case. The difference is probably due to the presence of several residual anastomoses instead of the single anastomosis found in this case. ...
... Table 1 Blood values before and after birth in the new donor and new recipient and quantification of the net AV blood flow between the 1st and the 2nd IUT (interval 1) and between the 2nd IUT and birth (interval 2). In the previous case, we calculated the net anastomotic blood flow by measuring only the decrease in total Hb [9] since the adult/ fetal Hb ratio had not been measured, resulting in 9.2 ml/24 h (interval 1) and 13.2 ml/24 h (interval 2), only slightly higher than the flows calculated using the reduction in adult Hb. The previous approach is inferior in methodology compared to the present method using only adult Hb values. ...
Twin-to-twin transfusion syndrome (TTTS) is due to unbalanced inter-twin blood flow through placental vascular anastomoses. We present a TTTS-case treated with fetoscopic laser surgery that allowed us to calculate the net inter-twin blood flow. In the weeks following laser treatment, the ex-recipient developed severe fetal anemia and was treated with two intrauterine adult red cell transfusions (at 26 and 29 weeks' gestation, respectively). After birth, placental injection with color-latex identified a single residual arterio-venous anastomosis from the ex-recipient to the ex-donor. We measured the fetal and adult hemoglobin concentrations in the anemic fetus before and after both intrauterine transfusions, and in both twins at birth. On the basis of these measurements, we calculated the blood flow across the residual arterio-venous anastomosis and found it to be 5.8+/-1.5 mL/24h after the 1st transfusion and 11.4+/-2.9 mL/24h after the 2nd transfusion.
... Therefore, comparable with previous work [5e8], we sought to analyze the benefits and risks of sequential laser therapy to aid facilitating its more widespread introduction. We simulated the response of the twins to realistic transfused volumes of blood utilising our computational model of TTTS [9,10] and the scarcely reported individual AV transfusions versus their arterial or venous diameters [2,11,12]. We inferred the range of possible AV dimensions that may be observed during fetoscopy from postnatal analysis of non-lasered TTTS placentas. ...
... From their data the TTTS case could not be identified. Third, in a case of incomplete laser therapy, resulting in the Twin AnemiaePolycythemia Sequence requiring an intra-uterine transfusion 2 days before emergency delivery, our group measured 28 ml/24 h (1.17 ml/h) through four residual AV anastomoses at 29 weeks [12]. From postnatal placental dye injection the internal diameter of these anastomoses was about 0.5 mm. ...
Sequential laser therapy of twin-twin transfusion syndrome (TTTS) includes laser obliteration of arteriovenous (AV) anastomoses from donor to recipient (AVDR) before obliterating AV anastomoses from recipient to donor (AVRD). This strategy allows for a beneficial intra-operative transfusion of blood from the hypervolemic recipient to the hypovolemic donor. In the present study, we sought to analyze the benefits and risks of sequential laser therapy with our computational model to aid its more widespread introduction. We simulated an equally shared placenta with an AVDR and a smaller diameter AVRD causing TTTS at 20 weeks. Laser coagulation and various volumes and directions of inter-twin transfusion were simulated at 21 weeks. A typical result is that when an AVDR is coagulated first, and 10 min later the AVRD with inner diameter of about 1 mm, an inter-twin transfusion of 25 ml may result from the recipient to the donor, based on literature data of AV flow versus diameter. This procedure causes a simulated loss of 50% of the recipient's blood volume. The opposite coagulation sequence, thus coagulating the AVRD first, 10 min later followed by the AVDR of 1 mm inner diameter, causes a loss of the donor's blood volume of 64%. In conclusion, our simulations support the concept of sequential laser therapy for TTTS and suggest directions for an improved safety and efficacy of this strategy.
... Not much is known about single anastomotic blood flow rates. Two studies reporting on anastomotic blood flow showed very different results, between 11.6 mL/min with intra-amniotic Doppler measurements [12] and 5.6 mL/24 h based on calculation of decreasing hemoglobin levels between intrauterine transfusion and birth [13] . The first one being highly unlikely due to the fact that the amount of flow exceeds the total blood volume of a midgestation fetus, currently no reliable technique exists to assess single anastomotic blood flow. ...
Objective:
To assess the impact of laser power and firing angle on coagulation efficiency for closing placental anastomoses in the treatment of twin-twin transfusion syndrome.
Methods:
We used an ex vivo blood-perfused human placenta model to compare time to complete coagulation using 30 vs. 50 W of neodymium-doped yttrium aluminum garnet laser power and using a firing angle of 90? vs. 45?. Placentas were perfused with pig blood at 5 mL/min. Differences were analyzed using independent-samples t test, Mann-Whitney U test, or ?2 test as appropriate.
Results:
Coagulation took less time and energy using 50 W (n = 53) compared to 30 W (n = 52), 11 vs. 22 s (p < 0.001), and 557 vs. 659 J (p = 0.007). Perpendicular coagulation (n = 53) took less time and energy compared to a 45? angle (n = 21), 11 vs. 17 s (p = 0.004), and 557 vs. 871 J (p = 0.004). Bleeding complicated 2 (3%) measurements in the 50-W group, 5 (10%) in the 30-W group, and 3 (14%) in the 45? group.
Discussion:
In a highly controlled model, a 50-W laser power setting was more energy efficient than 30 W in coagulating a placental vein. A more perpendicular laser firing angle resulted in more efficient coagulation. Furthermore, bleeding due to vessel wall disruption occurred more often with lower power and a more tangential approach.
... Finally, minuscule vascular anastomoses have also been discovered underneath the placental surface using a casting technique with latex injection. In this study, placental casting was not performed and the presence of deep-hidden anastomoses was not evaluated (van den Wijngaard et al., 2007). In conclusion, vascular anastomoses are extremely rare (and almost non-existent) in DC placentas, but ubiquitous in MC placentas. ...
Placental vascular anastomoses in twins lead to a shared circulation and may subsequently enable the development of severe complications such as twin–twin transfusion syndrome (TTTS) and twin anemia–polycythemia sequence (TAPS). The presence of vascular anastomoses has frequently and systematically been studied in monochorionic (MC) placentas, but only rarely in dichorionic (DC) placentas. The aim of this study was to compare the prevalence of vascular anastomoses and evaluate the sharing discordance in MC and DC placentas. All consecutive placentas of MC and DC twins delivered at the Leiden University Medical Center (the Netherlands) and Medical University of Warsaw (Poland) from 2012 to 2015 were routinely injected with colored dye and included in the study. We excluded twin pregnancies treated with fetoscopic laser surgery. A total of 258 placentas were analyzed in this study, including 134 MC placentas and 124 DC placentas. Vascular anastomoses were present in 99% (133/134) of MC placentas and 0% of DC placentas (
p
< .01). Placental share discordance between MC twins was significantly larger compared to DC twins, 19.8 (interquartile range [IQR] 8.1–33.3) and 10.8 (IQR 6.2–19.0), respectively (
p
< .01). Vascular anastomoses associated complications occurred in 16% (22/134) MC twins. Our findings show that vascular anastomoses are almost ubiquitous in MC placentas, but non-existent in DC placentas. In addition, unequal placental sharing appears to be more common in MC than in DC placentas.
... There are three types of vascular anastomoses: arteriovenous (AV), arterioarterial (AA) and venovenous (VV) anastomoses. The AV anastomoses are formed at the capillary level within shared cotyledon and carry unidirectional blood from one twin to the other, which may result in chronic fetal transfusion, such as twinetwin transfusion syndrome (TTTS) and twin anemiapolycythemia sequence (TAPS) [1]. The AA and VV anastomoses are respectively created by direct connection of arteries and veins from each twin. ...
... Estas comunicaciones facilitarían intercambios sanguíneos unidireccionales, lentos y persistentes en el tiempo, lo que asociado a la discrepancia de peso intergemelar, conducirían a la aparición progresiva de anemia en el ex receptor y policitemia en el ex donante (3,6,13). Lopriore y cols (14,15), estimaron que la velocidad del flujo en estas comunicaciones A-V minúsculas debiese ser alrededor de 5-15 mL/24 horas. gemelos se hizo crítica. ...
Presentamos la descripción del diagnóstico y manejo de una secuencia anemia-policitemia (SAP) que se presenta como complicación de una terapia láser exitosa en un embarazo gemelar monocorial cursando una transfusión feto-fetal (TFF) severa. Describimos la manifestación de esta complicación tardía de la terapia láser de la TFF severa y realizamos una revisión de la literatura internacional al respecto. A pesar del éxito de la introducción de la terapia láser en cuanto a la sobrevida y secuelas neonatales, recientemente se han descrito una serie de complicaciones de presentación tempranas o tardías. Entre las tardías, destacan la muerte de uno o ambos gemelos, recidiva de la TFF, y aparición de una SAP. Varios autores han descrito que la SAP sería secundaria a la presencia, o persistencia, de comunicaciones vasculares extremadamente pequeñas de flujo lento, las cuales llevan a una discordancia en los niveles de hemoglobina entre ambos gemelos, sin diferencias en sus volúmenes sanguíneos.
... There are three types of vascular anastomoses: arterio-arterial (AA), veno-venous (VV) and arterio-venous (AV) anastomoses. AV anastomoses have a unidirectional blood flow and may lead to an uncompensated inter-twin blood transfusion, which can result in twinetwin transfusion syndrome (TTTS) [1]. In contrast, AA and VV anastomoses allow bidirectional blood flow thus theoretically providing compensation for imbalanced flow due to the AV anastomoses. ...
... The largest analysis concerning long-term neurodevelopmental outcome after TTTS with laser surgery was published by Lopriore et al . [26]. They investigated 278 children at two years of age (corrected for prematurity). ...
Aim of the study: Newborns from multiple pregnancies are increasing in number and demonstrate a higher perinatal morbidity and mortality compared to singletons. Prematurity is the main reason for most neonatal diseases in twins, but other variables may play a role and their prenatal evaluation may improve the overall outcome. Main findings: Prematurity is six times more frequent in twins and therefore birth weight is significantly lower compared to singletons. Thus, twins are more exposed to prematurity related diseases (respiratory, cardiovascular, infectious, etc.) and to long-term complications (especially neurological disabilities). Results: It is very difficult to estimate the increased risk of neonatal morbidity related to twinning independently to the increased risk of prematurity and therefore to interpret data on morbidity rates, in particular regarding the neurodevelopmental outcome. Conclusion: Prevention of preterm birth is a primary goal in managing multiple pregnancies, together with prophylaxis with corticosteroids in order to improve foetal lung maturity. Accurate risk assessment strategies and adequate obstetrical-neonatological management of multiple pregnancies may reduce the increasing need for neonatal intensive care and for health resources in the long-term follow-up that has been observed over the last decades.
... Two spontaneous TAPS patients were treated with fetoscopic laser surgery after diagnosis and were thus excluded from the study. One post-laser TAPS patient was excluded because of the presence of a (small) superficial arterio-arterial anastomosis on placental injection (Lopriore et al., 2007c). Nineteen twin pairs thus fulfilled the inclusion criteria for this study. ...
To evaluate the neonatal hematological features of monochorionic twins with twin anemia-polycythemia sequence (TAPS) and to determine the additional diagnostic value of reticulocyte count measurement.
A cohort of consecutive monochorionic twins with TAPS (n = 19) was included in the study and each twin pair was compared with two monochorionic twin pairs (n = 38) unaffected by TAPS or twin-twin transfusion syndrome (TTTS), matched for gestational age at birth. We measured full blood counts on day 1 and determined the incidence of anemia, polycythemia, reticulocytosis and thrombocytopenia.
Median inter-twin hemoglobin (Hb) difference in monochorionic twins with and without TAPS was 13.7 g/dL and 2.4 g/dL, respectively (p < 0.01). Median inter-twin reticulocyte count ratio in twins with and without TAPS was 3.1 and 1.0, respectively (p < 0.01). Thrombocytopenia (platelet count < 150 x 10(9)/L) occurred more often in the TAPS group than in the control group, 45% (17/38) versus 11% (11/38), respectively (p < 0.01). In the TAPS group, mean platelet count was significantly lower in recipients than in donors, 133 x 10(9)/L versus 218 x 10(9)/L, respectively (p < 0.01).
TAPS twins have a large inter-twin Hb difference in combination with a large inter-twin reticulocyte count ratio. Recipients are more often thrombocytopenic than donors, probably due to polycythemia.
... As the intrauterine blood transfusion is administrated to the new donor, presence of adult hemoglobin in the new recipient is an irrefutable evidence of feto-fetal transfusion through a patent anastomosis. We recently discussed this issue in a similar TTTS case treated with intrauterine blood transfusion after incomplete laser (Lopriore et al., 2007c). In another case report, measurement of adult hemoglobin after birth also allowed us to determine the inter-twin transfusion rate . ...
Twin anemia polycythemia sequence (TAPS) is a consequence of unequal sharing of red blood cells between monochorionic twins resulting in anemia in the donor and polycythemia in the recipient twin. Prenatally TAPS can occur spontaneously or complicate incomplete laser surgery for twin transfusion syndrome. While there may be clinical overlap with twin transfusion syndrome or selective fetal growth restriction, diagnosis relies on Doppler measurement of middle cerebral artery peak systolic velocities. Significantly discordant velocities are diagnostic, while severity staging is based on signs of cardiovascular compromise. Conservative management, fetoscopic laser coagulation, selective twin reduction, fetal blood and exchange transfusion and delivery may be selected guided by the gestational age of diagnosis, the severity of the condition, likelihood of success and the patients priorities. Prenatal curative treatment that minimizes the risk for prematurity and residual morbidity at birth is most likely to offer the greatest short and long term benefits.
With an increasing incidence of twin gestations, understanding the inherent risks associated with these pregnancies is essential in modern obstetrics. The unique differences in placentation in twins contribute to the increased risks. Monochorionic twins are susceptible to complications because of their unique placental architecture, including twin-to-twin transfusion syndrome, the twin anemia-polycythemia sequence, selective intrauterine growth restriction, and the twin reversed arterial perfusion sequence. Knowing the clinical correlations of placental anatomy in these gestations helps perinatal pathologists perform a more informed placental evaluation, allowing for better care for the mother and her children.
Introduction
Twin anaemia-polycythaemia sequence (TAPS) occurs when significant haemoglobin discordance exists between monochorionic fetuses. Most reported cases occur iatrogenically after twin-to-twin transfusion syndrome (TTTS) laser therapy; spontaneous TAPS is also reported. The purpose of this study was to investigate pregnancy management and immediate neonatal outcomes for monochorionic multiple pregnancies complicated by TAPS referred to the NSW Fetal Therapy Centre (FTC).
Methods
Retrospective cohort study of multiple pregnancies referred to NSW FTC between April 2006 and April 2014. Fourteen TAPS cases [discordant middle cerebral artery peak systolic volume (MCA-PSV) or clinician diagnosis antenatally, or Hb >20 g/dL vs. <12 g/dL post-natally] were compared to an existing TTTS database (n = 142) and uncomplicated monochorionic diamniotic (MCDA) twin pregnancies (n = 45). Outcomes measured were maternal demographics; ultrasound findings at referral; management, including whether in utero fetal therapy was performed; and pregnancy outcome, including gestation at birth, mode of birth, birthweight, fetal/neonatal complications and neonatal survival to discharge.
Results
The majority of TAPS cases were spontaneous (9/14) and occurred later in pregnancy than TTTS (median gestation at diagnosis 26.0 ± 4.9 vs. 20.4 ± 2.6 weeks, P < 0.001). However, TAPS perinatal outcome was similar to TTTS (survival of both twins 62% vs. 53%, survival of at least one twin 85% vs. 87%, overall survival 73% vs. 70%) and overall survival significantly lower than for uncomplicated MCDA pregnancies (73% vs. 98%, P < 0.001).
Conclusion
Overall mortality for TAPS was similar to that of TTTS but significantly higher compared to uncomplicated MCDA pregnancies, underscoring the potential severity of TAPS despite its later gestational onset.
We describe the diagnosis and management of twin anemia-polycythemia sequence (TAPS), which occurs as a late complication of successful laser therapy in twin monochorionic pregnancies developing severe twin to twin transfusion syndrome (TTTS). We offer a description of this late complication of laser therapy in this condition and a review of the related medical literature. Despite the successful introduction of laser therapy on the survival and neonatal sequelae, various early and late complications related to this procedure have been recently described. Among the late, stands out the death of one or both twins, recurrence of TTTS, and the appearance of TAPS. With regards TAPS, several authors have reported that it would be secondary to the presence, o persistence, of extremely small slow flow vascular communications, which lead to discrepancies in the hemoglobin levels between the twins, with no differences in blood volume.
Introduction
Twin anemia-polycythemia sequence (TAPS) is a newly described form of chronic twin transfusion. Previous observational studies noted a discordance between birth weight and individual placental share in TAPS. The purpose of this study was to investigate if fetal growth in monochorionic (MC) twins with TAPS is determined by placental share or by the net inter-twin blood transfusion.
Methods
All consecutive MC twin placentas of live-born twin pairs with and without TAPS examined at our center between June 2002 and February 2014 were included in this study. Hemoglobin (Hb) levels and individual placental share were evaluated at birth and correlated with birth weight share. We excluded MC twin pregnancies with twin-twin transfusion syndrome.
Results
A total of 270 MC twin pregnancies (TAPS group, n=20; control group without TAPS, n=250) were included in this study. Donors with TAPS had a lower birth weight than recipients in 90% (18/20) of cases, but a larger placental share in 65% (13/20) of cases. In the TAPS group, birth weight share was positively correlated with Hb share at birth (P<0.01) but not with placental share (P=0.54). In the control group without TAPS, birth weight share was strongly correlated with placental share (P<0.01) but not with Hb share (P=0.14).
Discussion
A relatively larger placental share may enable the survival of the anemic twin in TAPS.
Conclusion
In contrast with uncomplicated MC twins, fetal growth in MC twins with TAPS is determined primarily by the net inter-twin blood transfusion instead of placental share.
Twin anemia-polycythemia sequence (TAPS) is a recently described complication of monochorionic placentation characterized by discordance in hemoglobin (Hgb) levels in the absence of amniotic fluid abnormality characteristic of classical twin-twin transfusion syndrome (TTTS). The placental angioarchitecture that predisposes to TAPS consists of small diameter arteriovenous anastomoses and the absence of balancing arterioarterial anastomoses. This vascular pattern occurs sporadically in 3 to 5% of monochorionic twins or iatrogenically following 2 to 13% of selective fetoscopic laser surgeries for TTTS. The diagnosis is based on measurement of the middle cerebral artery peak systolic velocity (MCA-PSV) which is not part of the Quintero staging for TTTS. With mild disease increased MCA-PSV in the anemic donor twin and a decreased MCA-PSV in the recipient twin are characteristic while severe disease is associated with critical Doppler findings, hydrops or single twin demise as in TTTS. Treatment options include fetoscopic laser, fetal blood transfusion, conservative management, and often preterm delivery. The most promising approach to TAPS is its prevention since the iatrogenic form comprises the majority of cases. When the fetoscopic laser technique is modified by coagulating the chorionic plate along the vascular equator (equatorial dichorionization or "Solomon" technique) the incidence of postlaser TAPS and recurrent TTTS is significantly reduced, survival is improved, and there is no increase in complications.
To evaluate neonatal outcomes and clinical characteristics of monochorionic diamniotic (MD) twins with a large intertwin hemoglobin (Hgb) difference at birth.
This was a retrospective cohort study of MD twin gestations delivered at Osaka Medical Center and Research Institute for Maternal and Child Health between 2003 and 2012. Cases of abortion, acardiac twins, or intrauterine death were excluded in this study. A large intertwine Hgb difference at birth was defined as >8.0g/dL according to the postnatal criteria for twin anemia-polycythemia sequence (TAPS). The intertwin reticulocyte count ratio (RCR) was calculated by dividing the reticulocyte count of the anemic twin by that of the polycythemic twin. Cases with Hgb differences were divided into two groups according to the RCR, TAPS when the RCR was >1.7 and acute feto-fetal hemorrhage (AFFH) when the RCR was ≤1.7. Neonatal outcomes were compared between the TAPS and AFFH groups.
During the study period, 432 out of a total of 532 MD twins born at our hospital were analyzed. There were 12 (2.8%) cases of a large intertwin Hgb difference. The median gestational age at birth was 34 weeks (range, 23-38 weeks), and all cases were delivered by cesarean section (CS). There were seven (1.6%) cases of TAPS and five (1.2%) cases of AFFH. The neonatal survival rate was 92.3%, but 1 pair of twins with TAPS experienced neonatal death. All (100%) cases with TAPS and two (40%) cases with AFFH required blood transfusion or partial exchange transfusion for at least one infant.
Although the incidence of TAPS and AFFH may be low in MD twins, many affected neonates required treatment for hematological abnormalities. In all cases of AFFH, the twins were delivered via CS; therefore, CS for MD twins does not appear to prevent AFFH.
Objective:
This study aimed to compare the angio-architecture of monochorionic placentas of spontaneous twin anaemia-polycythemia sequence (TAPS) with placenta of twin-to-twin transfusion syndrome (TTTS) with residual anastomoses after laser coagulation and placentas of uncomplicated monochorionic twin pregnancies.
Methods:
This case-control study compares the angio-architecture of monochorionic placentas of spontaneous TAPS (n = 12) with that of monochorionic placentas of TTTS treated by laser coagulation with residual anastomoses (TTTS + RA; n = 20) and placentas of monochorionic pregnancies without complications (n = 24), matched for gestational age. Placental sharing and angio-architecture were assessed by injection of colored dye.
Results:
The median diameter of the arterio-venous (AV) anastomoses in TAPS placentas was 2.26, 0.215 with TTTS + RA and 4.17 mm in normal monochorionic pregnancies (p < .03). The mean diameter of the arterio-arterial (AA) anastomoses in monochorionic placentas with spontaneous TAPS was 0.2 mm versus 0.15 mm in TTTS + RA and 2.0 mm in normal pregnancies, respectively (p < 0.03, p < 0.007). The number of AA anastomoses was lower with TAPS (0.3 versus 0.50 and 1, respectively, p < 0.015, p < 0.0001). Besides, unequal sharing was more frequent in TAPS as compared with monochorionic normal pregnancies (75% versus 29%, p = 0.03).
Conclusion:
Age matched placentas of spontaneous TAPS are characterized by very small AV anastomoses and very few AA anastomoses of smaller diameter than placentas of monochorionic twins with TTTS or without obvious complications.
Twin anemia-polycythemia sequence (TAPS) results from slow inter-twin blood transfusion through minuscule placental vascular anastomoses and is characterized by large inter-twin hemoglobin differences in the absence of amniotic fluid discordances. The optimal management for TAPS is not clear. We report a case of TAPS detected antenatally by Doppler ultrasound examination at 15(+6) weeks' gestation. After counseling, the parents opted for an expectant management. Bi-weekly Doppler measurements were performed and remained fairly stable. An emergency Caesarean section was performed at 34(+5) weeks. The donor was severely anemic (hemoglobin level 4.3 g/dL) while the recipient twin had severe polycythemia-hyperviscosity (hemoglobin level 25.4 g/dL). On day 1, he developed respiratory insufficiency and subclinical status epilepticus. MRI showed a total loss of grey-white matter differentiation as sign of severe diffuse cerebral ischemia and bilateral intra-and extra axial hemorrhages. There was almost complete lack of arterial and venous cerebral blood flow. On day 3, intensive care treatment was withdrawn in view of the severity of the brain injury. This case report demonstrates that TAPS may lead to severe cerebral injury and fatal outcome in the recipient twin. The importance of antenatal Doppler ultrasound investigations and management dilemmas in TAPS are highlighted. Copyright © 2012 ISUOG. Published by John Wiley & Sons, Ltd.
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.
In last years, owing to the widespread availability of assisted-reproduction technology, multiple pregnancy rates in Western countries have increased. In twin pregnancies, an increased rate of gestational complications, intrauterine growth restriction (IUGR), preterm birth and severe perinatal conditions is present. These complications are more frequent in monozygotic twins compared to dizygotic twins as well as an increased relative risk of chromosomal abnormalities and congenital malformation. Monochorionic twins are at higher risk for complications, since they share a common placenta where an imbalance in unidirectional arteriovenous anastomoses can lead to twin–twin transfusion syndrome. This extremely dangerous condition, if not early identified, can determine severe fetal complications with mortality rates that, in case of no treatment, reaches 90%. Laser photocoagulation is the treatment of choice in severe twin-to-twin transfusion syndrome with high survival rate. IUGR occurs more frequently in MC twins and along with prematurity and perinatal pathology is considered an important determinant of developmental delay.
Fetoscopic laser coagulation of placental vascular anastomoses is considered to be the treatment of choice in severe twin-to-twin transfusion syndrome. The aim of fetoscopic laser surgery is to separate completely the inter-twin placental circulation. Incomplete laser coagulation may result in residual vascular anastomoses. The incidence and clinical implications of residual anastomoses in twin-to-twin transfusion syndrome treated with fetoscopic laser surgery has not yet been studied. We examined all placentas treated with fetoscopic laser surgery and delivered at our center between June 2002 and December 2005 with vascular injection using colored dyes. Presence of residual anastomoses was studied in association with adverse outcome and inter-twin hemoglobin difference at birth. Adverse outcome was defined as fetal demise, neonatal death or severe cerebral injury. The relation between residual anastomoses and placental localization (anterior or posterior uterine wall) was evaluated. A total of 52 laser-treated placentas were studied. Residual anastomoses were detected in 33% (17/52) of placentas. Adverse outcome was similar in the groups with and without residual anastomoses, 18% (6/34) and 29% (20/70), respectively (p=0.23). Large inter-twin hemoglobin differences (>5g/dL) were found in 65% (11/17) of cases with residual anastomoses and 20% (7/35) of cases without residual anastomoses (p<0.01). Anterior placental localization was not associated with a more frequent presence of residual anastomoses. In conclusion, residual anastomoses at our institution are seen in one-third of monochorionic placentas treated with fetoscopic laser surgery. Although residual anastomoses in our study were not associated with adverse outcome, they were often associated with neonatal hematological complications.
In this prospective cohort study, we evaluated the initial results of fetoscopic laser surgery for severe second trimester twin-to-twin transfusion syndrome (TTTS) treated at our centre.
A total of 100 consecutive pregnancies with severe second trimester TTTS treated at our centre with selective fetoscopic laser coagulation of vascular anastomoses on the placental surface between August 2000 and November 2004 were included in the study. Perinatal survival was analysed in relation to Quintero stage.
Median gestational age was 20 weeks at fetoscopy (range: 16-26) and 33 weeks at delivery (range: 18-40). Perinatal survival rate was 70% (139/200). The treatment resulted in at least one survivor at the age of 4 weeks in 81% of pregnancies. Perinatal survival was significantly higher when treatment was performed in the early Quintero stages (95% in stage 1, 76% in stage 2, 70% in stage 3, 50% in stage 4) (p = 0.02).
Results of fetoscopic laser surgery for TTTS in our centre are similar to those in specialised centres in other countries. Diagnosis and treatment in the early Quintero stages resulted in significantly higher perinatal survival.
To compare fetoscopic laser surgery with amniodrainage in the treatment of twin-to-twin transfusion syndrome (TTTS) diagnosed after 26 weeks of gestation.
A retrospective cohort study.
Leiden University Medical Centre, a tertiary referral hospital for fetal therapy.
Between January 1991 and February 2006, 21 TTTS cases were diagnosed and treated after 26 weeks of gestation.
Treatment of TTTS consisted of either amniodrainage or fetoscopic laser coagulation of vascular anastomoses.
Primary outcome: adverse outcome (intrauterine or neonatal death, major neonatal morbidity and/or severe cerebral injury). Secondary outcome: gestational age at birth.
Eleven TTTS cases were treated with amniodrainage and ten with laser surgery. Median gestational age at birth in the amniodrainage group and in the laser surgery group was 29 and 31 weeks, respectively (P = 0.17) All infants were born alive. Major neonatal morbidity occurred more often in the amniodrainage group than in the laser surgery group, 27% (6/22) and 0% (0/20), respectively (P = 0.02). Severe cerebral injury in the amniodrainage group and in the laser surgery group occurred in 23% (5/22) and 15% (3/20) of infants, respectively (P = 0.70). Neonatal mortality in the amniodrainage group and in the laser surgery group was 14% (3/22) and 0% (0/20), respectively (P = 0.23). Overall adverse outcome was 36% (8/22) in the amniodrainage group and 15% (3/20) in the laser surgery group (P = 0.17).
In TTTS diagnosed after 26 weeks of gestation, amniodrainage and laser surgery both result in 100% survival. However, infants born after laser surgery have less major neonatal morbidity.
Laser coagulation of anastomotic vessels on the placental surface is the treatment of choice in severe second trimester twin-to-twin transfusion syndrome (TTTS). This procedure is associated with technical difficulties when the placenta is located on the anterior side of the uterus. We describe a novel technique for fetoscopy in TTTS with completely anterior placenta where laparoscopy is used to guide safe percutaneous insertion of the fetoscope through the lateral abdominal wall and the dorsal side of the uterus.
Prospective controlled series of 16 TTTS pregnancies with completely anterior placenta (study group) treated with this novel technique. Studied outcomes were technical result of the procedure and perinatal survival. Outcome in the study group was compared with outcome of 49 TTTS pregnancies treated with conventional percutaneous fetoscopic laser without laparoscopy, 9 of these with partially anterior placenta (control group A) and 40 with lateral or posterior placenta (control group B).
In the study group, the procedure-related complication rate was 25% (4/16). In 1 case, uterine entry of the fetoscope from the lateral abdominal wall was not possible due to complex bowel adhesions. In 3 patients, intra-amniotic haemorrhage occurred after fetoscopic entry, preventing complete laser coagulation of anastomoses. One of these patients required 2 units of blood transfusion. The procedure-related complication rate in control groups A and B was 22% (2/9) and 5% (2/40), respectively (intra-amniotic haemorrhage n = 3, severe leakage of amniotic fluid into the peritoneal cavity, n = 1). Perinatal survival in the study group, control group A and control group B was 63% (20/32), 78% (14/18) and 70% (56/80), respectively.
Combined laparoscopy and fetoscopy is a novel technique that enables safe uterine entry and creates optimal visualisation for laser coagulation of inter-twin anastomoses in TTTS pregnancies with completely anterior placenta. The procedure-related complication rate and perinatal survival rate were similar compared to the conventional percutaneous technique. Procedure-related complications occur more often with partially or completely anterior placenta.
In monoamniotic twin pregnancies discordant for fetal anomaly, parents may opt for selective feticide. However, the normal co-twin remains at risk of sudden demise from cord entanglement. We report on three cases of successful selective feticide by cord occlusion combined with cord transection.
We describe technical details and outcome of three monoamniotic twin pregnancies discordant for fetal anomaly (two cases of anencephaly and one case of congenital heart block) in which cord occlusion was followed by transection of the cord using contact laser.
The fetoscopic cord occlusion and transection using laser was successfully performed at 15, 16 and 19 weeks gestation, respectively. In one case, amniotic fluid leakage occurred after fetoscopy. The surviving co-twins were born at 36, 38 and 36 weeks gestation, respectively; two of the three were born vaginally and they were all healthy.
In monoamniotic twins, selective feticide using laser occlusion and transection of the umbilical cord is technically feasible and can lead to near-term vaginal birth of healthy co-twins.
Twin-twin transfusion syndrome (TTTS) represents a pregnancy complication with a high risk for perinatal mortality and postnatal morbidity. Mathematical models have been utilized to examine the mechanisms of disease and potential treatment modalities. We developed four consecutive models based on pathophysiology mechanisms. Conceptually, these models remained simple, but with increased complexity in details. We present our models tutorially with the necessary equations expressed in words. The aetiology of TTTS was related to AV anastomoses from donor to recipient and their growth commensurate with placental growth. We assessed that natural growth of placenta and foetuses causes the diameter and length of the AV, as well as the AV's pressure gradient, to increase proportional to gestational age. The AV transfusion then increases faster than natural foetal growth. A progressively increasing discordance subsequently develops, not compensated for by foetal growth. A simulation is performed to show how this discordance in blood volumetric development causes successive discordances in other functions, particularly renal, circulatory, and cardio-vascular, resulting in disease progression to the various stages of TTTS. In conclusion, mathematical modelling of TTTS has provided an understanding of the sequence of events that leads to the various presentations of TTTS stages as well as the efficacy of therapies.
Invasive techniques such as amniocentesis and cordocentesis are used for diagnosis and treatment in fetuses at risk for anemia due to maternal red-cell alloimmunization. The purpose of our study was to determine the value of noninvasive measurements of the velocity of blood flow in the fetal middle cerebral artery for the diagnosis of fetal anemia.
We measured the hemoglobin concentration in blood obtained by cordocentesis and also the peak velocity of systolic blood flow in the middle cerebral artery in 111 fetuses at risk for anemia due to maternal red-cell alloimmunization. Peak systolic velocity was measured by Doppler velocimetry. To identify the fetuses with anemia, the hemoglobin values of those at risk were compared with the values in 265 normal fetuses.
Fetal hemoglobin concentrations increased with increasing gestational age in the 265 normal fetuses. Among the 111 fetuses at risk for anemia, 41 fetuses did not have anemia; 35 had mild anemia; 4 had moderate anemia; and 31, including 12 with hydrops, had severe anemia. The sensitivity of an increased peak velocity of systolic blood flow in the middle cerebral artery for the prediction of moderate or severe anemia was 100 percent either in the presence or in the absence of hydrops (95 percent confidence interval, 86 to 100 percent for the 23 fetuses without hydrops), with a false positive rate of 12 percent.
In fetuses without hydrops that are at risk because of maternal red-cell alloimmunization, moderate and severe anemia can be detected noninvasively by Doppler ultrasonography on the basis of an increase in the peak velocity of systolic blood flow in the middle cerebral artery.
Twin-to-twin transfusion syndrome (TTTS) is a complication of monochorionic twin pregnancies associated with high perinatal mortality and morbidity. Placental vascular anastomoses, almost invariably present in monochorionic placentas, are the essential anatomical substrate for the development of TTTS. According to recent studies, different pathophysiologic mechanisms may play a role. Diagnosis of TTTS is no longer based on neonatal criteria such as birth weight discordance and hemoglobin difference, but on strict prenatal ultrasound criteria. A significant evolution in prenatal care strategies and management options for patients with TTTS has occurred during the last decade. Endoscopic laser ablation of communicating placental vessels is a new treatment modality that has led to an increase in survival rates. In perinatology, a decrease in mortality rates may be associated with an increase in morbidity rates. Follow-up studies in infants with TTTS are shedding more light on the wide range of morbidity associated with TTTS, such as neurological, cardiac and renal sequelae. This review analyzes the possible pathophysiologic mechanisms involved, discusses the latest findings in diagnosis, therapy and prognosis, and focuses on neonatal and pediatric morbidity associated with TTTS.
We developed a mathematical model of twin-twin transfusion syndrome (TTTS) that includes a hydropic recipient twin, adding interstitial and intracellular fluid compartments, fetal congestive cardiac failure, and the dynamics of renin-angiotensin system (RAS) mediators to our previous TTTS model. Ten differential equations for each twin, coupled by the net fetofetal transfusion of blood and blood components, i.e., colloids, osmoles, and RAS mediators, describe the development of fetal arterial and venous blood volumes, blood osmolality and colloid osmotic pressure (COP), interstitial fluid volume and COP, intracellular fluid volume, amniotic fluid volume and osmolality, and RAS mediator concentration. We included varying placental anastomoses, placental sharing, and amnionicity. The 20 differential equations were solved numerically from 0 to 40 wk with a 0.6-s time step. Consistent with clinical experience, model predictions are as follows. Unidirectional arteriovenous anastomoses and arteriovenous anastomoses inadequately compensated by oppositely directed anastomoses cause severe TTTS that includes a hydropic recipient. Adequately compensated arteriovenous anastomoses simulated TTTS without hydrops. The probability that oppositely directed anastomoses prevent onset of a hydropic recipient after TTTS onset, i.e., the largest interval between onset of TTTS and onset of hydrops in the recipient, was best for a venovenous anastomosis, closely followed by an arterioarterial and finally an oppositely directed arteriovenous anastomosis. Hydropic recipients have decreased amniotic fluid volume. Unequal placental sharing and amnionicity modify hydrops onset. In conclusion, our model simulates a sequence of events that results in a hydropic recipient twin in severe TTTS. The model may allow an assessment of the efficacy of current therapeutic interventions for TTTS cases that include a hydropic recipient twin.
Twin-twin transfusion syndrome in monochorionic twin pregnancies is not understood completely and is controversial which hampers development of acceptable diagnostic and rational treatment strategies. A haemodynamic model was developed that relates fetal growth with (1) fetoplacental blood flow and fetomaternal effects, and (2) net twin-twin transfusion from donor to recipient twin. Fluid balance mechanisms were neglected. Placental vascular anastomoses (arteriovenous, venoarterial, arterioarterial, venovenous) were modelled as straight blood vessels connecting the placental cord insertions that grow during pregnancy. Poiseuille's law predicts significantly decreasing anastomosing resistances, and when placental sharing is unequal it is assumed that smaller placental fractions cause smaller blood volumes and pressures. Two coupled first-order differential equations describing each twin's blood volume were determined and analysis showed that placental and anastomotic development cause anastomotic blood flow to increase faster than fetal growth. Hence, it is proposed as the syndrome's underlying pathophysiology that fetal discordance increases progressively, beyond fetal compensatory capacity. Fewer anastomoses cause larger discordance, but its onset can vary widely during pregnancy. Arteriovenous plus compensating anastomoses produce dynamic steady-state growth patterns with large, opposite, measurable anastomotic blood flows. Clinical study of fetal growth patterns may identify the syndrome's underlying placental anatomy. Predicted trends depend only weakly on implemented fetal physiology and are most likely realistic. This knowledge could improve future management of the syndrome.
(1) To calculate the feto-placental volume (FPV), using the haematocrit (Ht) values and the percentages of fetal haemoglobin (HbF), before and after red blood cell transfusion. (2) To estimate the transfusion-induced loss of plasma fluid.
Retrospective analysis of data of 42 anaemic fetuses at the first transfusion [gestational age (GA) 19-36 weeks].
Department of Obstetrics, Leiden University Medical Centre, The Netherlands.
Fifteen hydropic and 27 non-hydropic fetuses.
Donor blood volume (V(donor)) and Ht (Ht(donor)), fetal pre- and post-transfusion Ht values (Ht(initial), Htfinal) and percentages of HbF (HbF(initial) and HbF(final)) were used to calculate the FPV. The total red cell volume after transfusion (RCV(final)) and Ht(final) were used to estimate the plasma fluid loss.
Feto-placental blood volume and loss of plasma fluid.
The equations that use Htfinal over-estimate the FPV when the formula does not account for the difference between donor and post-transfusion Ht (FPV(Ht) = 21.36 * GA, - 390; r = 0.89). FPV is underestimated (FPV(Ht) = 9.90 * GA - 172; r = 0.84) when the blood volume increases with a volume less than the added donor blood volume. The calculation of FPV, using HbF percentages and the initial fetal RCV, is independent of volume changes (FPVHbF = 15.10 * GA - 279; r = 0.85). Comparing RCV(final) and Ht(final) values showed that 31.1 +/- 14.5% of the transfused volume was lost. Results of the hydropic fetuses did not differ from those of the non-hydropic fetuses.
FPV values based on Ht values are less reliable than those based on RCV and HbF findings. When, for practical reasons, Ht values have to be used, we propose an adapted equation for the calculation of the necessary volume of donor blood: V(donor) = FPV(HbF) * (Ht(final) - Ht(initial) / (Ht(donor) - 0.70 * Ht(final)).
We aimed to determine rates of interfetal transfusion along arterio-arterial (AA) anastomoses in monochorionic twins in vivo from analysis of Doppler waveform patterns. Twenty-one monochorionic twin pregnancies in which an AA anastomosis was identified antenatally underwent serial Doppler velocimetry. Unidirectional AA anastomotic flow rates increased with increasing gestational age (log y = 8 x 10(-9)x - 5 x 10(-8); p = 0.0002). The mean net rate of flow through an AA anastomosis at 28 weeks gestation was 7.6 x 10(-8) l/s (SD = 4.9 x 10(-8) l/s). This flow was significantly related to the distribution of arterio-venous (AV) anastomoses (p = 0.009) and birthweight discordancy (p = 0.006). We derived estimates of flow along individual AV anastomoses by assuming that net AA countertransfusion is shared equally among uncompensated AV anastomoses, and speculate that the median AV flow rate at 28 weeks is in the order of 6 x 10(-8) l/s. In conclusion, this study demonstrates that flow rates along AA anastomoses can be quantified antenatally. These are the first estimates of flow rates in vivo along placental anastomoses. Although AA net flows are modest, chronic unbalanced counterflow of this magnitude in the absence of compensatory superficial anastomoses could lead to significant haemodynamic compromise.
