Real-World Experience of Direct Oral Anticoagulant Use in a Single Pediatric Center

Abstract

Background: Pediatric venous thromboembolism (VTE), a disease comprising deep venous thrombosis and pulmonary embolism, has increased by 130-220%. Anticoagulation therapy is the mainstay of treatment, and direct oral anticoagulants (DOACs) offer several advantages. Recently, two DOACs (Dabigatran and Rivaroxaban) have been approved for use in children in the United States. Nonetheless, DOACs have been used "off-label” in children on an individualized basis, subject to approval from insurance plans. This study aims to evaluate real-world epidemiological and outcome data from a single-center cohort of pediatric patients treated with DOACs. Methods: In this single-center, IRB-approved study, 54 patients from the pediatric hematology oncology VTE database were identified and analyzed using SPSS statistical software, and a descriptive statistical analysis was conducted. Results: Epidemiological features: Of the 54 patients, 21 (39%) subjects were males, and 33 (61%) were females. Ages ranged from 4 to 22 years, with a mean age of 16.3 years. The majority of the subjects, 94%, were greater than 12 years old. Most (94%) of patients had venous thrombosis, 2% had an arterial thrombus, and 4 % had both arterial and venous. A breakdown of primary thromboembolism location highlights that the majority, 30%, had a pulmonary embolism on diagnosis, and the most common risk factors included obesity, catheterization, and infection (Tables 1 and 2). Of the 54 patients, 11% were started on DOACs as their initial anticoagulation treatment, 82% were switched to a DOAC on follow-up after initial treatment with heparin or low molecular weight heparin; four patients (7%) were started on DOACs after recurrent VTE on another anticoagulant. Twenty-one (39%) patients were on Apixaban, 32 (59%) were on Rivaroxaban, and 1 (2%) was on Dabigatran. One patient transitioned from Rivaroxaban to Apixaban due to an allergic reaction to the medication. Patients were on various durations of therapy ranging from 3 months to an extended duration depending on their clinical status and risk factors. Outcomes on DOACs: One (2%) patient had a major bleeding episode per ISTH definition. This was an episode of tonsillar artery bleeding status post tonsillectomy that required cauterization and surgical mesh placement in the operating room. Of the 33 females, two were premenarchal at the time of anticoagulation; therefore, 4 (13%) had evidence of heavy menstrual bleeding (HMB) that required medical intervention. HMB was identified by patients’ recall of menstrual bleeding; only one patient had a pictorial blood loss assessment chart (PBAC) score. Per ISTH definitions, 5 (9%) had clinically relevant non-major bleeding, including 4 patients with HMB and one additional patient with bloody diarrhea secondary to underlying ulcerative colitis that required medical intervention. One patient (2%) had minor bleeding with bloody secretions from a chest tube resulting in temporary holding of anticoagulantion. Five (9%) had recurrent VTE while on a DOAC (2 were on Apixaban, and 3 were on Rivaroxaban) and were transitioned to other forms of anticoagulation. Conclusion: The bleeding and recurrent VTE rates after DOACs appear comparable to other anticoagulants in pediatric VTE; heavy menstrual bleeding should be investigated in adolescent females. Given the recent approval of DOACs for pediatric patients, additional multi-centered outcome studies are needed to determine recurrence and bleeding risks. Figure 1View largeDownload PPTFigure 1View largeDownload PPT Close modal