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Ttts/Taps/Tops Twin‐Twin Transfusion Syndrome and Twin Anemia Polycythemia Sequence “The“The historyhistory ofof manman forfor thethe ninenine monthsmonths precedingpreceding hishis birthbirth would,would, probably,probably, bebe farfar moremore interestinginteresting andand containcontain eventsevents ofof greatergreater momentmoment thanthan allall thethe threethree scorescore andand tenten yearsyears thatthat followfollow it.”it.” SamuelSamuel TaylorTaylor ColeridgeColeridge MiscellaniesMiscellanies AestheticAesthetic andand Literary,Literary, 18031803 Twin Anemia Polycythemia Sequence •A true form of feto‐fetotransfusion •Characterized by large intertwin hemoglobin differences without signs of twin oli/poly sequence •Occurs spontaneously in 3 to 5% of monochorionic diamniotic twins •Chronic transfusion via < 1 mm placental vessel •Occurs in 0.3 to 13% of cases after fetoscopic laser Twin Anemia Polycythemia Sequence •Doppler ultrasound abnormalities showing an increased •Increased peak systolic velocity in the MCA of donor twin •Consistent with anemia •Decreased MCA‐PSV in the recipient twin •Suggestive of polycythemia Donor Recipient Vacular connection Twin Anemia‐Polycythemia Sequence:Diagnostic Criteria, Classification,Perinatal Management and Outcome F. Slaghekke a W.J. Kist a D. Oepkes a S.A. Pasman a J.M. Middeldorp aF.J. Klumper a F.J. Walther b F.P.H.A. Vandenbussche a E. Lopriore b. Fetal Diagn Ther 2010;27:181–190 Twin Anemia Polycythemia Sequence Antenatal Findings at Doppler Ultrasound Examination Stage 1: MCA‐PSV donor >1.5 MoM and MCA‐PSV recipient <1.0 MoM, without other signs of fetal compromise Stage 2: MCA‐PSV donor >1.7 MoM and MCA‐PSV recipient <0.8 MoM, without other signs of fetal compromise Stage 3 as stage 1 or 2, with cardiac compromise of donor, defined as critically abnormal flow* Stage 4 hydrops of donor Stage 5 intrauterine demise of one or both fetuses preceded by TAPS * Critically abnormal Doppler is defined as absent or reversed end‐diastolic flow in umbilical artery, pulsatile flow in the umbilical vein, increased pulsatility index or reversed flow in ductus venosus. Twin Anemia Polycythemia Sequence Treatment Options Survival •Observation 75% •Intra‐uterine transfusion 100% •Fetoscopic laser 100% •IUT and Fetoscopic Laser 100% •Selective fetocide 50% •Termination of pregnancy 0% Twin Anemia‐Polycythemia Sequence:Diagnostic Criteria, Classification,Perinatal Management and Outcome F. Slaghekke a W.J. Kist a D. Oepkes a S.A. Pasman a J.M. Middeldorp aF.J. Klumper a F.J. Walther b F.P.H.A. Vandenbussche a E. Lopriore b. Fetal Diagn Ther 2010;27:181–190 TWIN-TWINTWIN-TWIN TRANSFUSIONTRANSFUSION SYNDROMESYNDROME Unsolved problem • Most common complication in MC twins • 4-35% of all MC gestations in US • 0.1-0.9 per 1000 births • 17% of all perinatal mortality in twins • Mortality of 80-100% if untreated • Mortality of 15-63% even with treatment Twin-TwinTwin-Twin TransfusionTransfusion SyndromeSyndrome Diagnostic Criteria • Neonatal criteria - Discordant cord blood Hgb > 5 g/dl - Discordant birth weight > 20% • Non-TTTS meeting criteria - 19/130 had Hgb > 5 g/dl - Growth restriction without TTTS - Fetal acidosis, hypoxemia - Polycythemia • Discordant Hgb rare in TTTS • Discordant weight common in TTTS - ? threshold of >20% Twin-TwinTwin-Twin TransfusionTransfusion SyndromeSyndrome •Echocardiogram •Fetal MRI Diagnostic Evaluation •Ultrasound • Monochorionic gestation • Oligohydramnios DVP < 2cm • Polyhydramnios DVP > 8cm • Doppler velocimetry changes • Donor • AEDF in UA • Complete absence of DF in UA • Recipient • Pulsatile UV • AEDF in UA • DV: decreased, absent, reversed a wave • Growth discordance TTTSTTTS DIAGNOSISDIAGNOSIS OFOF EXCLUSIONEXCLUSION •15% cases not TTTS •TTTS mimicked by • Placental insufficiency • Dichorionic gestation • Discordant anomaly • Discordant viral infection • Klippel-Trenaunay- Weber FetalFetal MRIMRI FindingsFindings inin TTTSTTTS Recipient Donor Cases Cases Hydrops/ 15% 6% Ascites Brain Bleed/ 15% 3% Ischemia Demise 4% 6% TwinTwin TwinTwin TransfusionTransfusion SyndromeSyndrome TTTS Cardiomyopathy • Cardiac decompensation • More afterload pathology • Not volume stress • Isolated tricuspid regurgitation • RV hypertension Systolic P> 80 mmHg • Pulmonary outflow tract obstruction • Pulmonary insufficiency • Pulmonary atresia/intact ventricular septum • Elevated Endothelin I • Fisk et al 1998 • Recipent twins hypertensive as newborns • Tolosa et al 1993 EchocardiographicEchocardiographic FindingsFindings inin TTTSTTTS •Myocardial hypertrophy RV > LV •Decreased compliance RV > LV -Monophasic inflow •AV valve incompetence TV > MV •Poor compliance/ AV valve incompetence reflected in •DV abnormalities -Decrease in a wave -Absence of a wave -Reversal of a wave •Acquired congenital heart disease -Pulmonic valve stenosis, insufficiency, atresia -Not reversible with treatment of TTTS EndothelinEndothelin--11 LevelsLevels inin TTTSTTTS From Bajoria et.al., Human Reproduction 1999; 14(6) ReninRenin--AngiotensionAngiotension SystemSystem (RAS)(RAS) inin TTTSTTTS CardiacCardiac SequelaeSequelae:: RecipientRecipient TwinTwin Volume Overload CardiacCardiac SequelaeSequelae inin TTTS:TTTS: DonorDonor TwinTwin • Less in utero abnormality • Abnormal postnatal arterial function - Decreased arterial distensibility - Related to vascular changes related to low vascular volume/flow? - Risk of later hypertension? QuinteroQuintero StagingStaging ofof TTTSTTTS Stage I: Discordant amniotic fluid: DVP >8 cm & < 2 cm Stage II: Absent bladder in the donor Stage III: Doppler velocimetry changes in UA, UV, DV Stage IV: Hydrops Stage V: Death of one fetus AcuteAcute CardiacCardiac ChangesChanges inin TTTSTTTS Quintero Staging I II III IV V Donor Recipient AEDF in UA Severe biventricular failure Reversal of flow in DV Severe TR/MR Reversal of flow in UA rec Early TTTS Endstage TTTS Staging is heavily weighted toward the donor Recipient findings on in advance stage III and IV NIHNIH TTTSTTTS TrialTrial Logistic Regression Analysis of Covariates Cardiovascular Profile Score (CVPS) Normal -1 point -2 points Hydrops None Ascites, pleural skin edema pericardial effusion Venous Dopplers Normal DV atrial reversals Venous pulsations 10/10 CT Ratio < 0.35 > 0.35< 0.5 > 0.5 Abnormal myo- Vent SF > 0.28 SF < 0.28 cardial function No AV regurg TR or semi lunar TR +dysfunction valve regurg any MR Abnormal Normal AEDF REDF Arterial Dopplers Cardiovascular Profile Score (CVPS). From Huhta, J Perinat Med 29:390-398, 2001 NIHNIH SponsoredSponsored TTTSTTTS TrialTrial Logistic Regression Analysis of Covariates on Survival • Recipients - Cardiovascular Profile Score* - Most predictive of poor recipient outcome - OR = 3.025/point - p = 0.054 • Donors - Most predictive models of poor outcome - Increased Stage - OR = 0.446/stage p = 0.124 - Earlier Gestational Age - OR = 1.052/day p = 0.097 *Huhta et al J Perinat Med 29:390‐398, 2001 ImpactImpact ofof FetalFetal EchocardiographicEchocardiographicF Findingsindings onon RecipientRecipient SurvivalSurvival •Cardiovascular Profile Score (CVPS) •62 consecutive recipient twins with TTTS • 3 stage IV • 26 stage III • 33 stage I or II • All patients treated by SFLP • All patients had pre-operative echo evaluated • Blinded to outcome Michelfelder et al Ultrasound Obstet Gynecol 30: 965‐71, 2007 Shah AD, et al:J Am Soc Echocardiogr 2008 TR jet RecipientRecipient SurvivalSurvival FollowingFollowing SFLPSFLP BasedBased onon PrePre--OperativeOperative CVPSCVPS p< 0.03 p< 0.008 Survival Recipient % CVPS ProblemProblem withwith thethe CVPSCVPS Normal -1 point -2 points Hydrops None Ascites, pleural skin edema pericardial effusion Venous Dopplers Normal DV atrial reversals Venous pulsations CT Ratio < 0.35 > 0.35< 0.5 > 0.5 Abnormal myo- Vent SF > 0.28 SF < 0.28 cardial function No AV regurg TR or semi lunar TR +dysfunction valve regurg any MR Abnormal Normal AEDF REDF Arterial Dopplers Cardiovascular Profile Score (CVPS). From Huhta, J Perinat Med 29:390-398, 2001 Not sensitive enough TTTSTTTS Cardiomyopathy Cardiomyopathy • Fetal hypertensive cardiomyopathy • 3 parameters of cardiomyopathy - AV valve competence - Mild, moderate, severe TR/MR - Hypertrophy - End-diastolic LV, RV, Septum - Myocardial dysfunction - Tei myocardial performance index FetalFetal CareCare CenterCenter ofof CincinnatiCincinnati Cincinnati Modification of Quintero TTTS Staging Stage I Stage II Stage III IIIA Mild cardiomyopathy IIIB Moderate cardiomyopathy IIICSevere cardiomyopathy Stage IV Stage V EchocardiographicEchocardiographic FeaturesFeatures ofof TTTSTTTS byby StageStage Incidence of TR and MR 100 90 80 70 60 Tricuspid 50 Regurgitation 40 Mitral 30 Regurgitation 20 10 0 III IIIACincinnati IIIB Stage IIIC IV Cincinnati Stage EchocardiographicEchocardiographic Features Features ofof TTTSTTTS byby Biventricular Hypertrophy StageStage Incidence of Biventricular Hypertrophy 100 90 80 70 60 50 Biventricular 40 Hypertrophy 30 Percent 20 10 0 III IIIA IIIB IIIC IV Cincinnati Stage AssessingAssessing RecipientRecipient TTTSTTTS CardiomyopathyCardiomyopathy Tei Myocardial Performance Index Tei C, et al. New index of combined systolic and diastolic myocardial performance: a simple and reproducible measure of cardiac function--a study in normals and dilated cardiomyopathy. J Cardiol 1995;26:357-66 Eidem BW, et al: Quantitative assessment of fetal ventricular function: establishing normal values of the myocardial performance index in the fetus. Echocardiography 2001;18:9-13 Ichizuka K et al, The Tei index for evaluation
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