• Disease Overview
  • Synonyms
  • Signs & Symptoms
  • Causes
  • Affected Populations
  • Disorders with Similar Symptoms
  • Diagnosis
  • Standard Therapies
  • Clinical Trials and Studies
  • References
  • Programs & Resources
  • Complete Report

Twin Anemia Polycythemia Sequence


Last updated: May 20, 2021
Years published: 2021


NORD gratefully acknowledges Enrico Lopriore, MD, PhD, Head of Department of Neonatology, Willem-Alexander’s Children’s Hospital, Leiden, The Netherlands, and Stephanie Ernst, Founder, TAPS Support Foundation for the preparation of this report.

Disease Overview

Twin anemia polycythemia sequence (TAPS) is a rare but severe complication in identical twin pregnancies that share a single placenta (monochorionic). TAPS is caused by an imbalance in red blood cells exchanged between the twins through tiny placental blood circulations (anastomoses). This leads to too few red blood cells (anemia) in the donor twin and too many red blood cells (polycythemia) in the recipient twin. TAPS was first described in 2006,1 and being a relatively “new” disease; it is sometimes confused with the better-known twin-to-twin transfusion syndrome (TTTS).

However, TAPS is a separate disease with characteristic pathogenesis, diagnostic criteria, classification system, and outcome.

TAPS is a chronic and slow imbalance in blood flow between the babies, happening at any time during the pregnancy. It causes chronic anemia and polycythemia without an imbalance in the amniotic fluid between the twins, a characteristic of TTTS that often leads to maternal symptoms due to the rapid growth of the mother’s stomach.

Unlike TTTS, TAPS has no physical symptoms due to no fluid differences in the babies and often remains undiagnosed. This is why Doppler ultrasound measurements on the mid-cerebral artery are vital during pregnancy, as this is the only reliable way to detect TAPS.

Treatment options for TAPS before birth include expectant management ( “watch and wait”), premature delivery, intrauterine transfusion with or without partial exchange transfusion, laser surgery, and in very severe cases, selective reduction of the pregnancy.

The best management option is currently still unknown. The management and outcome in TAPS can vary in severity from case to case, depending upon when during pregnancy the syndrome occurs, when a diagnosis is made, and what treatments are performed.

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  • TAPS
  • feto-fetal transfusion syndrome
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Signs & Symptoms

Before birth, TAPS may go undetected due to lack of symptoms and the lack of excess amniotic fluid (polyhydramnios) like in TTTS. TAPS can be detected using Doppler ultrasound examination, focusing specifically on the blood flow (peak systolic velocity, PSV) in the middle cerebral artery (MCA). In the donor, the MCA-PSV is increased as a sign of fetal anemia. In the recipient, the MCA-PSV is decreased as a sign of polycythemia.

Although routine MCA-PSV measurements are proven to be an adequate predictor for TAPS, it has been challenging to implement Doppler screening for TAPS in the bi-weekly ultrasound check-ups for monochorionic twins. Other signs on ultrasound may also be a starry sky liver in the recipient and placental dichotomy (a bright appearance to the donor’s share of the placenta). At birth, signs and symptoms are more evident as the donor is strikingly pale and the recipient is purple/red color (plethoric). The placenta must be examined, and blood testing completed to confirm the diagnosis.

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Tiny blood vessels in the shared placenta that connects the babies’ umbilical cords and blood circulations (anastomoses) cause TAPS. These connections are present in all monochorionic twin pregnancies. In most cases, the blood flow stays relatively balanced through these connecting blood vessels. However, in TAPS, the blood between the two babies is not balanced. One baby, the donor, gives more blood to the other, the recipient, leading to the donor becoming anemic and the recipient polycythemic.

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Affected populations

TAPS is a rare disorder affecting a small number of monochorionic twin pregnancies. Many cases go undiagnosed and unrecorded; the actual frequency is unknown.

All too often, TAPS is only diagnosed at birth when one baby is pale while the other is red. TAPS happens spontaneously in 5% of all monochorionic pregnancies (spontaneous TAPS) and can also occur in TTTS pregnancies after incomplete laser surgery (post-laser TAPS) due to small missed or incompletely sealed connections.

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TAPS can be detected during pregnancy by Doppler ultrasonography. Ultrasound findings in TAPS include twins of the same gender; a single, shared placenta (monochorionic), a thin membrane dividing the babies’ amniotic sacs; no differences in amniotic fluid (TTTS); and the presence of discordant MCA-PSV Dopplers.

The current staging system for TAPS follows the one proposed by Tollenaar et al.2. Like TTTS, this classification system may suggest that TAPS follows an orderly progression over time. However, this is not the case, and it can progress in highly variable and unpredictable ways.

When physicians examine the placenta after delivery, this can confirm the twins’ monochorionic status. The placenta must be injected with colored dye to detect the tiny connecting blood vessels because these are not visible to the naked eye.

The maternal side of the placenta shows a remarkable color difference with a pale side of the donor and a darker and congested side of the recipient. At birth, doctors must check the hemoglobin and reticulocytes of the babies. In TAPS, hemoglobin discordance is more than 8 g/dL. The reticulocyte count in the donor is higher due to chronic anemia and increased red blood cell production (erythropoiesis). Reticulocyte ratios are measured by dividing the reticulocyte count of the donor by the recipient. In TAPS cases, the difference is more than 1.7.

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Standard Therapies

Outcome and Treatment

Outcomes in both spontaneous and post-laser TAPS are problematic and associated with an increased risk of permanent injury and death. Adverse effects of TAPS are mainly due to complications related to prematurity. Long-term outcomes in TAPS show an increased risk of bilateral deafness and neurodevelopmental impairment in donors 3. Hearing loss was detected in 15% of donors, but the cause is not entirely clear.

Specialized hearing screening should be performed in all TAPS survivors to ensure that hearing loss is detected in a timely manner. Early intervention is vital to avoid speech and language developmental delays.

Fetoscopic laser surgery is a treatment option for TAPS, but evidence for optimal treatment is still lacking. The TAPS Trial is working on determining the best treatment for TAPS by comparing laser surgery with other treatment methods.4

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Clinical Trials and Studies

Information on current clinical trials is posted on the Internet at www.clinicaltrials.gov. All studies receiving U.S. government funding, and some supported by private industry, are posted on this government website.

For information about clinical trials being conducted at the NIH Clinical Center in Bethesda, MD, contact the NIH Patient Recruitment Office:

Toll-free: (800) 411-1222
TTY: (866) 411-1010
Email: [email protected]

Some current clinical trials also are posted on the following page on the NORD website:

For information about clinical trials sponsored by private sources, in the main, contact:

For more information about clinical trials conducted in Europe, contact:

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1. Lopriore E, Middeldorp JM, Oepkes D, Kanhai HH, Walther FJ, Vandenbussche FP. Twin anemia-polycythemia sequence in two monochorionic twin pairs without oligo-polyhydramnios sequence. Placenta. 2007 Jan;28(1):47-51.

2. Tollenaar LSA, Lopriore E, Middeldorp JM, Haak MC, Klumper FJ, Oepkes D, Slaghekke F. Improved prediction of twin anemia-polycythemia sequence by delta middle cerebral artery peak systolic velocity: new antenatal classification system. Ultrasound Obstet Gynecol. 2019 Jun;53(6):788-793.

3. Tollenaar LSA, Lopriore E, Slaghekke F, Oepkes D, Middeldorp JM, Haak MC, Klumper FJCM, Tan RNGB, Rijken M, Van Klink JMM. High risk of long-term neurodevelopmental impairment in donor twins with spontaneous twin anemia-polycythemia sequence. Ultrasound Obstet Gynecol. 2020 Jan;55(1):39-46.

4. The TAPS Trial https://en.thetapstrial.com/

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