Severe adverse events related to vitamin K antagonists in children with congenital or acquired heart disease

Abstract

Although increasingly used, vitamin K antagonists (VKA) remain difficult to manage for children with congenital or acquired heart disease (CAHD). To assess the occurrence of thrombosis and major bleeding events in children with CAHD treated with VKA and to determine associated risk factors. All children enrolled in the VKA dedicated educational program between 2008 and 2020 were prospectively included. Clinically suspected thrombotic events were confirmed by imaging, while major bleedings were defined according to the ISTH. Time in therapeutic range (TTR) was calculated to evaluate the stability of anticoagulant therapy. Statistical analysis included Cox proportional hazard models. We included 390 patients, median age at initiation was 6.6 (IQR: 12.8–3.2) years. Median follow-up was 17.7 months. The median TTR was 85.2% (IQR: 95.3%–74.4%). Thirteen thrombosis in 9 (2.3%) children and 24 major bleedings in 17 (4.4%) children were reported. At 6 years, 86.6% (CI95% [75.6%–92.4%]) and 95% (CI95% [89%–97.8%]) of patients were free of major bleeding and thrombotic events, respectively. In univariate analysis mitral valve replacement (MVR) was associated to major bleeding events (HR 3.32 [1.16–9.44], P = 0.025). In multivariable analysis, recurrent minor bleeding events (≥ 3) (HR 4.9 [1.7–13.8], P = 0.002) and global TTR under 70% (HR: 3.6 [1.1–10.9], P = 0.04) were risk factors associated to major bleeding events whereas MVR did not reach the level of significant association (HR: 1.92 [0.6; 5.9], P = 0.25). In multivariable analysis, Kawasaki disease (HR: 11.84 [2.7–52.6], P = 0.001) and global TTR under 80% (HR: 5.05 [1.2–20.7], P = 0.025) were main risk factors for thrombotic events. Overall, VKA use appears to be safe and effective in children with CAHD. Patients with Kawasaki disease and those with a TTR under 80% are at highest risk of thrombosis. A TTR under 70% and minor recurrent bleeding events are the main risk factors for major bleeding events.