Obligatory etiology

Obligatory etiology. Twin–twin transfusion syndrome

In obligatory TTTS, the placental vascular design is deterministic or fatalistic. The faulty placental vascular design consists of the presence of either more numerous or larger arteriovenous (AV) anastomoses from donor to recipient. As a result, more blood flows from donor to recipient. To investigate this hypothesis, we assessed the size, number, and direction of arteriovenous anastomoses. Demonstration of faulty placental vascular design: The DR score 3 Detailed endoscopic analysis of the size, number, and direction of AV anastomoses in TTTS placentas indeed suggests larger or more numerous AV anastomoses from donor to recipient.

In a study we conducted on 20 TTTS patients with pure AV anastomoses identified endoscopically during laser surgery, the number of vascular communications was established in two ways:
• as a single communication, if only an artery and a vein participated
• as multiple communications, if prolific branching precluded an accurate estimate of the number of vessels.


For single communications, the vessel size used for the calculations was that of the largest participating vessel. For areas with multiple communications, the vessel size used was that of the largest vessel immediately prior to the branching. Vessel size was subjectively classified as hair, small, medium, or large (Figure 3.1).

A relative weight of ?1 (small), ?1.4 (medium), or ?1.9 (large) was assigned for the different vessel sizes, based on visual observations. The direction of flow of AV communications, whether from donor (AVDR) or from recipient (AVRD) was established by tracing back the artery to the corresponding fetus of origin, knowing that arteries cross over veins. Four additional patients had superficial arterioarterial (AA) or venovenous (VV) anastomoses. Because the direction of flow in AA or VV communications could not be established, these patients were excluded from the analysis. The net direction of blood flow in each case was determined by performing an algebraic sum of the AV communications using Poiseuille’s law for capillary flow:

where q is flow rate, C is a constant to account for unit conversion, r is the radius of the capillary, p is pressure, B is the volume factor of the fluid, m is viscosity, and L is the length of the capillary. Although differences in blood pressure, fluid viscosity, and vessel length could be present, the prevailing factor in the equation is the radius of the blood vessel, elevated to the 4th power. An algebraic sum of the weighted flow in each case (?AVRDs – ?AVDRs) yielded a donor recipient (DR) score (Figure 3.2).

Table 3.1 shows the number, size, and direction of the communications and the corresponding DR score for each individual case in the 20 patients studied. The mean number of communications was 4.1 (range 1–8). Communications were bidirectional (i.e. both AVDRs and AVRDs were present in the same placenta) in 18/20 (90%) of cases. In 2 patients, a single unidirectional AVDR was found. Eighty percent of cases had a negative DR score, suggesting indeed a net exchange of blood from donor to recipient. Two patients had a positive DR score, suggesting an apparent net flow of blood from recipient to donor. This most likely represents the relative imprecision of vessel size assessment.

To test the validity of the conclusion with regard to the sensitivity of the measurement, we tabulated the DR score for varying ranges of relative vessel size. Table 3.2 shows different scenarios for the medium- and large-sized vessels considered (1.2–1.6 for the medium, and 1.7–2.1 for the large; Figure 3.3). As can be seen, the minimum percent of negative DRs in the worst scenario is 75%.

Actually, even if with extreme relative sizes, such as ?1, ?10, and ?100 for small, medium, and large vessels, the results of the DR score remain unchanged. This means that the key element in the assessment of the size of the anastomosis is the subjective qualification of the vessel as small, medium, or large. Misjudgment of the relative vessel sizes within the same patient is unlikely, as one can continuously compare their sizes during surgery. Differences in size assignment between patients do not alter the results, since the DR score is performed individually.

Our subsequent assessment of the size, number, and direction of AV anastomoses in a total of 400 TTTS patients has shown the presence of at least one AVDR in all cases. In no instance were there communications only from recipient to donor (AVRDs). Sixteen cases (4%) had communications only from donor to recipient (AVDRs).

The endoscopic analysis of the number, size, and direction of AV anastomoses suggests that a vascular anatomical basis may indeed be responsible for the development of TTTS in a subset of patients. Although the actual amount of blood exchange can only be estimated from this assessment, a larger number or larger size of AVDRs suggests that, indeed, a net flow of blood may take place from donor to recipient twin and be responsible for the syndrome.

Persistent or reverse twin–twin transfusion syndrome as further evidence of the obligatory etiology 

Persistent or reverse TTTS may result from patent anastomoses left after laser therapy for TTTS. The anastomoses may have been overlooked altogether, or, as in most cases, sublasered. Patients with persistent TTTS will show one or more patent AVDRs.

Patients with reverse TTTS will show one or more patent AVRDs. If the opportunity permits, a second laser procedure will allow identification and lasering of the patent anastomosis. Resolution of the syndrome occurs invariably. Thus, cases where a single anastomosis, AVDR or AVRD has been left patent, constitute an unintended iatrogenic experimental demonstration of the obligatory pathophysiological mechanism for TTTS. The following case illustrates the point.

The patient was a gravida-2, para-1 at 17.6 weeks’ gestation referred with the diagnosis of TTTS. She had not undergone genetic or therapeutic amniocentesis. Ultrasound confirmed the presence of a monochorionic, diamniotic twins with a posterior placenta.

The maximum vertical pocket (MVP) in the recipient was 8.6 cm, and 0.9 cm in the donor. The bladder of the donor twin was visible and Doppler studies were not critically abnormal, making it a stage II disease (see Chapter 7). During surgery, 4 AV anastomoses were identified and photocoagulated: from donor to recipient, 1 large, 1 medium, from recipient to donor; 1 large and 1 small.

A follow-up ultrasound on the first post-op day revealed a normal fetal heart rate for both twins. The patient returned with reverse TTTS at 24.3 weeks’ gestation. The MVP in the former recipient sac was 1.4 cm and 12.8 cm in the sac of the former donor. The patient underwent a second procedure during which two small AV communications were ablated (one from donor to recipient, one from recipient to donor). Symptoms of TTTS did not recur. The patient delivered two viable female infants at 34 weeks’ gestation. Surgical pathology revealed no residual patent anastomosis.