Abstract
Background:
Kawasaki disease (KD) is the leading cause of acquired heart disease in children in developed countries, typically presenting in children under age 5 with fever, rash, and lymphadenopathy. Coronary artery dilation and aneurysms are the most serious long-term complications, occurring in up to 25% of untreated children. Large aneurysms significantly increase the risk of acute thrombosis and myocardial ischemia, with at least 10% developing aneurysmal thrombosis (McCrindle et al., 2020). Children with coronary aneurysms of Z score ≥10 or absolute diameter ≥8 mm are typically managed with combined antiplatelet and anticoagulant therapy—most often low molecular weight heparin (LMWH) or vitamin K antagonists (VKAs). Recently, direct oral anticoagulants (DOACs) such as apixaban have emerged as safe, effective alternatives, offering oral administration, stable dosing, and fewer drug interactions. While routine anti-Xa monitoring is not required for DOACs in standard indications, the high thrombotic risk in KD and evolving pediatric dosing strategies may justify titration to higher peak levels.
Methods:
This study aimed to describe our institutional practice using apixaban for thromboprophylaxis in children with KD and large coronary aneurysms, and to report associated thrombotic and bleeding outcomes. To support this patient population, we established a monthly joint cardiology-hematology clinic for KD patients requiring long-term thromboprophylaxis. After at least 6 months of enoxaparin and/or warfarin, patients are eligible to transition to weight-based, twice-daily apixaban. In the absence of a liquid formulation, 2.5 and 5 mg tablets are split, crushed, and suspended in liquid by the family. Drug levels are measured using anti-Xa assays calibrated to apixaban, with the first level obtained ~2 weeks after initiation, targeting 200–300 ng/mL. If within range, a second level is drawn 2 weeks later. Once two levels are therapeutic, monitoring occurs every 3–6 months; dose adjustments prompt rechecking 1–2 weeks later.
We conducted a retrospective chart review of KD patients with large coronary aneurysms transitioned to apixaban between January 2024 and July 2025 at our institution. Primary endpoints were thrombosis and bleeding, categorized using ISTH criteria for major, clinically relevant non-major (CRNM), and minor bleeding. The secondary endpoint was the number of dose adjustments.
Results:
Twenty patients with KD who were transitioned to apixaban were identified. A diagnosis of KD with large coronary artery aneurysms or significant coronary artery dilation was made between 2009 and 2024. Four patients developed coronary artery thrombi though none occurred while on apixaban – 1 at the time of diagnosis, 2 while on enoxaparin, and 1 while off anticoagulation. There were no major bleeding events observed. All minor bleeding events that occurred while on apixaban also occurred while on enoxaparin or warfarin (epistaxis, n=6). All patients received single or dual anti-platelet therapy during their treatment course. Median apixaban dose adjustments for the cohort were one, with five patients requiring 3 or more dose changes. In patients with significantly elevated peak levels > 300 ng/ml, bleeding complications were not observed (n=6). Thirteen patients had levels <200ng/mL requiring dose increases.
Conclusion:
This descriptive, retrospective chart review highlights the real-world use of apixaban for thromboprophylaxis in high-risk KD patients with large coronary artery aneurysms or dilation. Despite the small sample size and limited follow-up, our findings suggest that apixaban is a safe and effective option in this population. However, important limitations remain. Pediatric dosing is weight-based, and the lack of flexible formulations can make dose adjustments challenging. Additionally, it remains unclear whether routine monitoring of apixaban levels for this population is necessary, particularly given the wide variability in drug levels observed—both in our study and others (e.g., Vanderpluym 2023)—without associated bleeding or thrombotic events. Nonetheless, our findings are encouraging, as apixaban may offer a safer, more convenient alternative that improves quality of life for children with KD and giant coronary aneurysms.
