Intermediate term thrombotic risk in contemporary total cavo-pulmonary connection for single ventricle circulations

Abstract

Despite the common occurrence of thrombosis in Fontan circulations, the mid-term thrombotic risk beyond the first two postoperative years is poorly defined especially in total cavo pulmonary Fontan. This study examines the thrombotic incidence and risk beyond the first 2 years after contemporary Fontan surgery. Using a retrospective cohort study design, 89 Fontan patients, 50 male, were included and evaluated with a median of 8.3 years (IQR 6.8-11.4) follow-up. Hospital records were reviewed for known risk factors of thrombosis, thrombotic events, antiplatelet and anticoagulation management, and basic characteristics. Forty seven patients (52%) had a dominant left ventricle, and 28 (32%) had hypoplastic left heart syndrome. Eight patients had thrombotic events post Fontan surgery at a median age of 9 years (IQR 5.6-13), 5.7 (IQR 2.0-9.7) years following surgery, not including events that occurred immediately peri-operatively. Four thrombotic events were intracardiac whereas the remainder were extra-cardiac. There was no significant univariate correlation between thrombosis and the presence of ventricular morphology, pulmonary arterial reconstruction, or type of cavopulmonary anastomosis (lateral tunnel vs. extracardiac conduit). Thrombosis continues to be an important intermediate-term risk even for patients with contemporary Fontan circulations. These results strongly suggest that thrombophilic risk is not dictated purely by vascular pathway and hemodynamic variables. Further investigation into the pathophysiology, individualized risk, and effectiveness of anticoagulation strategies are required in this high risk population.

Fontan-Associated Liver Disease: Pathophysiology, Staging, and Management

“…16 • Prothrombotic state: Thromboembolic events are a constant feature in Fontan patients due to the anatomical and functional characteristics of the Fontan circulation and to a state of thrombophilia. 17 Indeed, Fontan patients have a hypercoagulability state with low serum levels of antithrombin III, thrombomodulin, α2-antiplasmin, and C and S proteins and high levels of thrombin-antithrombin complex, similar to that observed in cirrhosis. 18 Microthrombosis has thus been proposed as another profibrogenic mechanism in an animal model of FALD, opening the door to exploration of the role of anticoagulation as an antifibrotic agent in this population.…”

Single-Ventricle Physiology

“…Single-ventricle patients have a multiplicity of risk factors that promote thrombosis, and it has been shown that thromboembolic events may affect up to 33% of patients, contributing to nearly 25% of mortalities, including death from pulmonary embolism and cerebrovascular accidents. 7,33,34 The underlying risk factors include the very crux of the Fontan, the passive, non-pulsatile venous flow through the pulmonary bed. Also included are chronic venous congestion, low cardiac output, dilated atrium, cardiac arrhythmia, and PLE.…”

“…The use of novel oral anticoagulants is promising; however, studies concerning their benefit in Fontan patients have yet to completed. 7,[33][34][35][36]…”

Long Term Consequences of the Fontan Procedure and How to Manage Them

“…Despite changes in the surgical design of Fontan, and although the AP Fontan has largely been abandoned, thrombosis continues to be a major problem following the Fontan procedure [64]. transitioned from VKA to NOAC therapy, and there were no reported adverse events in those who were started on a NOAC without prior anticoagulation [71].…”

“…The reported prevalence of thromboembolic (TE) events is as high as 33%, contributing to approximately 25% of mortalities via deep venous thrombosis, pulmonary embolism, or cerebrovascular accident[64][65][66]. Thrombosis risk factors include non-pulsatile pulmonary flow, low cardiac output, arrhythmias, type of Fontan connection, residual shunts or intentional fenestration, dilated atrium, ventricular dysfunction, hypoxia, liver disease, PLE, and underlying coagulation abnormalities[65][66][67].…”