Twin-to-twin transfusion syndrome and limb ischemia: a case report

Introduction

Twin-to-twin transfusion syndrome (TTTS) is the most important cause of death and handicap in a monochorionic twin pregnancy [15]. It was first described by the German gynecologist Friedrich Schatz in 1875. However, this was probably not the first case to be “illustrated”: a 17^th century painting in the Netherlands probably shows a deceased twin after TTTS [2]. If untreated, this condition has a very high mortality and even despite antenatal treatment, the morbidity in infants remains high [8–10]. Several treatment strategies are available for TTTS. Serial amniodrainage and selective laser photocoagulation (SLP) are most commonly used. SLP, however, shows less mortality and morbidity [15]. Although SLP is an expensive intervention, a recent cost-effectiveness analysis showed a favorable profile when compared with serial amniodrainage [13]. In utero acquired limb ischemia is a known complication of monochorionic twin pregnancies. It is more common among the recipient twins in TTTS and is most likely related to a disease process; the pathogenesis, however, remains unclear [4, 7].

Case report

A 17-day-old male neonate was referred together with his twin brother to a level-three neonatal intensive care unit for socio-geographic reasons and further evaluation and treatment for severe right lower limb ischemia. He was the first of twins born at a gestational age of 34 weeks delivered by emergency cesarean section for fetal distress of both twins after a pregnancy complicated by TTTS, diagnosed in early pregnancy. Because of the severity of the TTTS (stage IV by Quintero), SLP had been performed at 26 weeks at the referring hospital. This procedure was performed without any complications. Ultrasound scans performed during pregnancy did not detect any limb abnormalities in either twin. However, these scans focused on the detection of any recurrent TTTS, parameters of fetal well-being, and cardiac function. Except for the brain, heart, and kidneys, a systematic review of the entire anatomy is usually no longer performed. The infant was the former recipient in this condition.

At birth, he showed good Apgar scores of 8 both at 1 and 5 min; he weighed 1950 g. A necrotic right limb was noted immediately after birth. The necrosis consisted of a clear line of demarcation with signs of circumferential constriction at this level starting about 1 cm above the knee joint, and below this a pale lower limb was seen with prominent bone structures and vanishing soft tissue (Figure 1). The patient was admitted at the referring intensive care unit because of low birth weight, prematurity, and the necrotic limb. Besides hyperbilirubinemia, which was treated with phototherapy, no other neonatal complications occurred. Clotting profile showed no abnormalities; hence, no extra thrombophilic workup was performed. After referral to our center, surgical intervention was postponed until a clear line of demarcation was seen. Once the demarcation was clear (day 22), an amputation of the lower leg and knee joint was performed, with resection of a small part of the “healthy” femur to create a good stump. This procedure was performed without any complications. His brother showed no remarkable problems during his admission.

Figure 1

Picture taken shortly after birth showing necrosis of the right leg.

The necrotic part of the leg was sent for anatomic-pathological investigation. Macroscopic investigation showed a toe-heel distance of 2.2 cm. This is compatible with a gestational age of 16—18 weeks [5]. On microscopic investigation, there was no definite explanation for the necrosis, although anatomo-pathological findings strongly suggested a vascular thrombosis (Figure 2).

Figure 2

Picture showing vascular thrombosis of the right leg on anatomic-pathological investigation.

Discussion

Limb ischemia is a known complication of TTTS, which nearly always affects the recipient [7, 8]. The physiopathological mechanism resulting in this phenomenon is not yet fully understood. Although several hypotheses have been suggested, the role of the SLP has never been investigated. Moreover, none of the proposed hypotheses are conclusive.

Polycythemia has been proposed as a major contributing factor in its pathogenesis [3, 4]. Polycythemia, however, is a much more common finding in these children than limb ischemia, as stated by Lopriore et al. [11]. Although this difference in incidence does not rule out that polycythemia – and the associated hyperviscosity – plays a role in the cascade leading to limb ischemia, other mechanisms are likely to be involved as well.

These other hypotheses mainly focus on the hormones and peptides that influence the vascular system. The concentrations of endothelin, a potent vasoconstrictive peptide, are higher in recipients when compared with donors, which theoretically could influence the blood flow in these infants [1]. Yet, clinical implications of these findings remain highly uncertain. The renin-angiotensin system has also been proposed as a major contributing factor. Mahieu-Caputo et al. [12] showed that the renin expression is significantly different in both twins. The donor twin has an increased renin synthesis due to the relative volume depletion. This renin passes through the connections between the two and thereby increases blood pressure and vascular tonus in the recipient. These vascular changes might contribute to a pro-thrombogenic status. This mechanism was also confirmed in later studies [6].

SLP has not been clearly linked to limb ischemia in literature [4]. In our case, the limb necrosis was initially attributed to SLP. However, the size of the foot strongly suggested that the necrosis started at a gestational age well before the time of SLP (2.2 cm for 16–18 weeks compared with 4.8 cm for 26 weeks). Pathological examination thus refuted the proposition that SLP caused the limb ischemia in our patient. As a conclusion, our case supports the hypothesis that limb necrosis is most probably caused by the underlying disease process rather than by SLP. Physicians should be cautious to attribute this complication to SLP.