Vascular damage in Feto–Fetal Transfusion Syndrome

The interdependency of the two fetal circulations is highly specific of monochorionicity. This is also the main anatomical and functional support for the development of vascular disruptive cerebral lesions. Two theories were suggested in the early 1960s and in the 1990s by Benirschke5 and Larroche,25 respectively, to explain the pathogenesis of these lesions. There are two main circumstances associated with cerebral lesions and FFTS syndrome when both twins are alive as opposed to when one fetus has died in utero. In 1961, Benirschke proposed that pathological findings were compatible with an embolization phenomenon which could explain several visceral infarcts and lesions of necrosis.

These could only be found in one surviving twin next to its dead co-twin.5 This pathological mechanism suggested that necrotic debris and thrombocytoplastic substances elaborated in the dead twin or in its infarcted placenta could reach the surviving twin through placental vascular shunts, resulting in the occlusion of vessels or disseminated intravascular coagulation (DIC) and subsequent damage. Although this explanation was attractive, findings and it was never demonstrated in vivo. Necrotic emboli are therefore an unlikely phenomenon, owing to the dead twin’s inability to disseminate emboli in the survivor and particularly against its active pressure and because blood flow stops shortly after the death of one twin. Thrombosis was only demonstrated by Yoshioka et al26 in two infants, which were 5 and 12 months old at the time of diagnosis.

These two infants were born next to their macerated co-twin. Occlusion of the cerebral vessels was identified using angiography and suggested an embolic origin of the thrombosis. However, they would have also been compatible with a vasospasm or thrombosis due to an acute drop in blood pressure and blood volume in the immature cerebral vessels. In-utero DIC has never been confirmed in vivo in any surviving twin. However, this simplistic image of one twin being poisoned by its dead co-twin has imprinted perinatologists’ brains beyond generations and beyond reason owing to paragraphs copied from one textbook to the next and lacking critical analysis.

In 1991, Fusi et al27 even described one case of single intrauterine death in which no coagulation abnormality could be established in the survivor in utero using fetal blood sampling within days of the death of his sibling. In 1990 Larroche et al25 highlighted the state of hemodynamic imbalance related to the monochorionic condition. She supported the idea that this was the main and probably the only phenomenon involved in the development of brain lesions in monochorionic twins since it could occur just as well when both twins were alive. Although a chronic and overall unidirectional transfusion from one twin, the donor, to his sibling, the recipient, is likely to occur through placental vascular anastomoses, this can also evolve as an acute and massive28 phenomenon, leading to feto–fetal exsanguination.

Amnioreduction alters feto–fetal hemodynamics with acute changes in blood pressure both in donors and recipients.27 This can also occur following incomplete laser coagulation. This hemodynamic theory was confirmed by the consistent diagnosis of severe anemia in single survivors irrespective of their initial status of donor or recipient and by the constant finding of polycythemia in the dead twin both postnatally and in utero within hours following the death of one monochorionic twin.25,29–33 Jou34 and Gembruch35 have visualized reversal of the transfusion initiated towards the agonizing twin, near the time of its death, using color and pulsed Doppler examination.

The development of anemia in the surviving twin can accurately be monitored using Vmax in the middle cerebral artery (Vmax?MCA) by considering a cut-off value of greater than 1.5 MoM (multiple of the median) of the expected value. This avoids the need for fetal blood sampling in order to refine the risk to the survivor and it allows correction of severe anemia by intrauterine transfusion36 to be more selectively targeted at cases of fetal exsanguination. Although this may appear a lifesaving procedure, its influence on the development of cerebral lesions in the survivor should be further investigated.32,36