The Fontan pathway represents the surgical solution for all “non-septable” hearts, either due to underdevelopment or the complete absence of a cardiac chamber. In other words, the Fontan procedure is the definitive strategy for managing single-ventricle physiology. Achieving the Fontan stage requires two prior surgeries. In the neonatal period, based on the infant’s primary issue, one of the following procedures is performed:

• Reduced pulmonary flow: systemic-to-pulmonary shunt.
• Reduced systemic flow: stage 1 Norwood.
• Increased pulmonary flow: pulmonary banding.

Subsequently, at 4-6 months of age, once the initial treatment becomes insufficient, the Glenn surgery (superior cavopulmonary connection) is performed. Finally, between 2 and 4 years of age, the child’s growth allows the Fontan surgery to be carried out.

In his seminal 1971 article in Thorax, Francis Fontan clarified the intent of his procedure: “This is not an anatomical correction, which would necessitate the creation of a right ventricle, but rather a physiological restoration of pulmonary flow along with the suppression of left and right blood mixing.” This physiological solution comes at a price, leading to several maladaptations, including an increased prothrombotic state with unclear etiology.

Standard hemostasis tests do not provide sufficient information on coagulation status, particularly in Fontan circulation (FC) patients. In recent years, clinical practice has incorporated new technologies offering a more comprehensive assessment of coagulation. Among these, calibrated automated thrombography (CAT) evaluates the impact of various factors on thrombin formation. This technological advancement underpins the study we analyze today.

This research, conducted by a Polish team, included 81 adult FC patients from three tertiary hospitals. Healthy volunteers aged 18-40 years (n = 54) served as controls. Individuals with elevated total cholesterol levels, suspected thrombophilia, or pregnancy were excluded. To minimize confounding factors, anticoagulant and/or antiplatelet therapies were discontinued with sufficient lead time to obtain baseline hemostatic profiles. Three thrombin formation scenarios were evaluated: the influence of platelets, coagulation factors, and tissue factor derived from microparticles. Interest in microparticles has surged due to their apparent role in thrombus formation in systemic processes, including oncologic, inflammatory, and cardiovascular conditions.

Upon analyzing the data, Skorek et al. observed that 40% of the FC group exhibited thrombocytopenia, while most patients had elevated liver enzymes. Seventy percent were classified as NYHA functional class II, and half of the cohort was receiving anticoagulant or antiplatelet therapy. These findings align with expectations, including the decreased activity of coagulation factors V, VII, and X reported in FC patients. However, a 185% increase in microparticle-derived tissue factor was identified in the Fontan group (p < .001). Platelet influence demonstrated a reduced thrombin formation potential in the FC group (p < .001), persisting across subgroups stratified by antiplatelet use and thrombocytopenia (p < .001). These results were consistent regardless of systemic ventricle type or anastomosis configuration (extracardiac conduit/intracardiac conduit/atriopulmonary). Conversely, microparticle-derived tissue factor influence indicated greater thrombin formation potential (p < .001).

The authors concluded that microparticles, particularly the tissue factor derived from them, may significantly contribute to the prothrombotic state in FC.

COMMENTARY:

Interest in FC has risen in the literature, partly due to data emerging from national registries such as those in Australia and New Zealand. We know Fontan survival exceeds 80% at 30 years, with patients often enjoying a good quality of life, engaging in work, and leading nearly normal lives. Most patients will not require further surgical interventions, and fewer than 5% will undergo cardiac transplantation. These registries provide a more contemporary perspective, revealing outcomes better than expected. As a result, a growing cohort of patients with this unique circulation is likely to lead long lives. However, not all outcomes are favorable. Eight percent of these patients will experience symptomatic thrombotic events, with subsequent mortality exceeding 30%. Identifying, understanding, and addressing the complications associated with this circulation is imperative.

Non-pulsatile pulmonary flow, slowed venous return, hepatic congestion, Fontan prosthetic material, hypoxemia, and turbulence at cavopulmonary anastomoses cause endothelial damage. Damaged endothelial cells release microparticles and von Willebrand factor into the bloodstream. This groundbreaking study by Skorek et al. establishes a strong association between these microparticles and the prothrombotic state of FC. Their findings shed light on anticoagulation management in this population, an area with no scientific consensus. The endothelial involvement suggests new therapeutic targets.

Despite its novel contributions, the study has limitations. The sample size is small, although it represents the largest cohort of FC patients in Poland. The FC group is heterogeneous in anastomosis techniques, systemic ventricle types, and baseline medications (some on antiplatelets, others on anticoagulants). Additionally, the lack of follow-up data precludes evaluating the progression of the studied variables.

Thanks to studies like this, we begin to address some unanswered questions, though much remains to be learned regarding optimal treatment for single-ventricle hearts.

REFERENCE:

Skorek P, Skubera M, Natorska J, Ząbczyk M, Trojnarska O, Pająk J, et al. Dissimilarity in coagulation system in adults after Fontan surgery based on thrombin generations. Eur J Cardiothorac Surg. 2022 Dec 2;63(1):ezac550. doi: 10.1093/ejcts/ezac550.