Use of apixaban in children awaiting heart transplantation.

BACKGROUND: The use of apixaban in the pediatric cardiac population is expanding. We describe our apixaban dosing and monitoring strategy in children and young adults awaiting heart transplantation, along with outcomes related to bleeding and thrombosis during wait-list and early post-transplant periods. METHODS: This study is a retrospective, single-center analysis of all patients receiving apixaban while awaiting cardiac transplantation. Weight-based dosing was monitored with peak drug-specific anti-Xa chromogenic analysis. Significant post-operative bleeding defined by chest tube output or need for surgical intervention. RESULTS: From September 2020 to December 2022, 19 patients, median age 13.5 years (6.1, 15.8 years), weighing 48.9 kg (15.4, 67.6) received apixaban while awaiting transplant. Indication for apixaban was prophylaxis (n = 18, 3 with ventricular assist devices) and treatment of thrombus (n = 1). There were no clinically relevant non-major or major bleeding, nor thrombotic events while awaiting transplant. The median time from last apixaban dose to arrival in the operating room was 23.2 h (15.6-33.8), with median random apixaban level of 37 ng/mL (28.3, 59), 6.3 h (4.8, 8.4) prior to arrival in the operating room. In this study, 32% of patients had significant post-operative bleeding based on chest tube output post-transplant or need for intervention. No patients meeting criteria for significant post-operative bleeding were thought to be attributable to apixaban. CONCLUSIONS: Careful use of apixaban can be safe and effective while awaiting heart transplant. There was no appreciable increase in peri-operative bleeding. The use of apixaban is promising in providing safe, predictable and efficacious anticoagulation while avoiding additional patient stressors.

Real-world use of apixaban for the treatment and prevention of thrombosis in children with cardiac disease.

BACKGROUND: Direct oral anticoagulants use in pediatric cardiology is poorly defined. OBJECTIVE: We present the largest experience of apixaban use in children with heart disease, using weight- and level-based dosing. METHODS: Retrospective single-center analysis of cardiac patients ≤19 years treated with apixaban. Patients were evaluated for safety (clinically relevant non-major [CRNM] or major bleeding; thrombotic events) and effectiveness (thrombus improvement by imaging). Peak drug-specific anti-Xa chromogenic assay results ("apixaban levels") were analyzed. RESULTS: Over 3 years (5/2018-9/2021), 219 children, median age 6.8 years (0.3-19), median weight 20.8 kg (4.8-160) received apixaban, totaling 50,916 patient days. Of them, 172 (79%) warranted thromboprophylaxis and 47 (21%) thrombosis treatment (with 10 arterial, 19 venous, 15 intracardiac, and 3 pulmonary). The median initial peak apixaban level was 165 ng/mL (23-474; n = 125) in the prophylaxis subgroup and 153 ng/mL (30-450; n = 33) in the treatment subgroup; dosage was adjusted in response to levels in 25% of the patients. There were 4 bleeding safety events (3 CRNM; 1 major, hemoptysis complicating empyema); the serious bleeding event rate was 2.9 per 100 patient-years of apixaban. Minor bleeding events (42) were noted in 18 patients, with an additional 2 having leukopenia, 1 transaminitis, and 3 rashes. An improvement in thrombosis was seen in 95% of the treated patients with available follow-up imaging (37/39 patients). CONCLUSION: Apixaban use was feasible with a low rate of adverse events across a diverse pediatric cardiac population using commercially available tablets dosed to weight and adjusted based on peak apixaban levels.

Coagulation profiles and viscoelastic testing in multisystem inflammatory syndrome in children.

OBJECTIVE: To characterize viscoelastic testing profiles of children with multisystem inflammatory syndrome in children (MIS-C). METHODS: This single-center retrospective review included 30 patients diagnosed with MIS-C from March 1 to September 1, 2020. Thromboelastography (TEG) with platelet mapping was performed in 19 (63%) patients and compared to age- and sex-matched controls prior to cardiac surgery. Relationships between TEG parameters and inflammatory markers were assessed using correlation. RESULTS: Patients with MIS-C had abnormal TEG results compared to controls, including decreased kinetic (K) time (1.1 vs. 1.7 minutes, p < .01), increased alpha angle (75.0° vs. 65.7°, p < .01), increased maximum amplitude (70.8 vs. 58.3 mm, p < .01), and decreased lysis in 30 minutes (Ly30) (1.1% vs. 3.7%, p = .03); consistent with increased clot formation rate and strength, and reduced fibrinolysis. TEG maximum amplitude was moderately correlated with erythrocyte sedimentation rate (ESR) (r = 0.60, p = .02), initial platelet count (r = 0.67, p < .01), and peak platelet count (r = 0.51, p = .03). TEG alpha angle was moderately correlated with peak platelet count (r = 0.54, p = .02). Seventeen (57%) patients received aspirin (ASA) and anticoagulation, five (17%) received only ASA, and three (10%) received only anticoagulation. No patients had a symptomatic thrombotic event. Six (20%) patients had a bleeding event, none of which was major. CONCLUSIONS: Patients with MIS-C had evidence of hypercoagulability on TEG. Increased ESR and platelets were associated with higher clot strength. Patients were prophylactically treated with ASA or anticoagulation with no symptomatic thrombosis or major bleeding. Further multicenter study is required to characterize the rate of thrombosis and optimal thromboprophylaxis algorithm in this patient population.

Apixaban for treatment of intracardiac thrombosis in children with congenital heart disease.

Apixaban is well studied in adults; paediatric data are extremely limited. We describe 3 children (age 2-6 years, weight 13-17 kg) with congenital heart disease who developed intracardiac thrombosis, and in whom typical treatments had failed (in 1) or were considered impractical (in 2). All were treated with apixaban 2.5 mg orally twice daily with complete (in 2) or partial (in 1) thrombus resolution and no clinical bleeding events.

Utility of a dedicated pediatric cardiac anticoagulation program: the Boston Children's Hospital experience.

Congenital heart disease is the leading cause of stroke in children. Warfarin therapy can be difficult to manage safely in this population because of its narrow therapeutic index, multiple drug and dietary interactions, small patient size, high-risk cardiac indications, and lack of data to support anticoagulation recommendations. We sought to describe our institution's effort to develop a dedicated cardiac anticoagulation service to address the special needs of this population and to review the literature. In 2009, in response to Joint Commission National Patient Safety Goals for Anticoagulation, Boston Children's Hospital created a dedicated pediatric Cardiac Anticoagulation Monitoring Program (CAMP). The primary purpose was to provide centralized management of outpatient anticoagulation to cardiac patients, to serve as a disease-specific resource to families and providers, and to devise strategies to evolve clinical care with rapidly emerging trends in anticoagulation care. Over 5 years the CAMP Service, staffed by a primary pediatric cardiology attending, a full-time nurse practitioner, and administrative assistant with dedicated support from pharmacy and nutrition, has enrolled over 240 patients ranging in age from 5 months to 55 years. The most common indications include a prosthetic valve (34 %), Fontan prophylaxis (20 %), atrial arrhythmias (11 %), cardiomyopathy (10 %), Kawasaki disease (7 %), and a ventricular assist device (2 %). A patient-centered multi-disciplinary cardiac anticoagulation clinic was created in 2012. Overall program international normalized ratio (INR) time in therapeutic range (TTR) is favorable at 67 % (81 % with a 0.2 margin) and has improved steadily over 5 years. Pediatric-specific guidelines for VKOR1 and CYP2C9 pharmacogenomics testing, procedural bridging with enoxaparin, novel anticoagulant use, and quality metrics have been developed. Program satisfaction is rated highly among families and providers. A dedicated pediatric cardiac anticoagulation program offers a safe and effective strategy to standardize anticoagulation care for pediatric cardiology patients, is associated with high patient and provider satisfaction, and is capable of evolving care strategies with emerging trends in anticoagulation.