Athn 15: Characterizing the Real-World Use of Direct Oral Anticoagulants in Pediatric Patients - Interim Analysis

Background: There are currently four direct oral anticoagulants (DOACs) approved for the acute treatment and prevention of venous thromboembolism (VTE) in adults. Pediatric hematologists across the United States (US) are using DOACs for their patients based on extrapolated data from adult studies and recently published phase 3 pediatric-specific studies. (Brandao LR, et al. Blood, 2019 and Male C, et al. Lancet Haematol, 2020.)

Because further data regarding DOAC use in children are needed, ATHN 15: Characterizing the Real-World Use of Direct Oral Anticoagulants in Pediatric Patients, was developed and is being sponsored by the American Thrombosis and Hemostasis Network (ATHN). The study is being conducted at ATHN-affiliated sites in the US and aims to characterize the real-world use of DOACs in children diagnosed with VTE. ATHN is a nonprofit network of over 140 federally funded hemophilia treatment centers (HTCs) that provides the infrastructure for clinical research and public health surveillance.

Methods: Data being captured includes demographics, clinical characteristics, anticoagulation management, and treatment outcomes (bleeding and recurrent thrombosis) of patients <21 years of age, who have received or are receiving a DOAC since January 1, 2015 for the treatment of an acute VTE episode or prevention of thrombosis recurrence. Data are collected for up to 6 months from the start of DOAC treatment.

Results: As of May 31, 2020, 76 patients from 9 sites have been enrolled (see Table 1 for demographics). Deep venous thrombosis (DVT) of the lower extremities or pelvis is the most prevalent VTE (n = 23, 30.26%), followed by DVT of the upper extremity or upper thorax and pulmonary embolism plus VTE (n = 22, 28.95 and n = 13, 17.1% respectively). 82.89% of patients did not have a history of prior VTE at the time of enrollment. Of the 15 patients with a radiologically confirmed anatomic anomaly, Paget Schroetter/Thoracic Outlet Syndrome and May-Turner Syndrome are the most common (n = 6, 40% and n = 4, 26.7%, respectively). Factor V Leiden heterozygosity, reported in 8 patients, is the most prevalent inherited thrombophilia.

Forty-eight patients were identified as having a medical risk factor associated with their VTEs. Sixteen (33.3%) were classified as obese and another 13 (27.1%) had a hospital admission stay greater than 7 days and within 30 days prior to the VTE. At least one specific drug or environmental risk factor was reported in 44 patients. Concomitant use of hormonal contraception (currently taking/stopped within 4 weeks prior to VTE) and the presence of a central venous catheter (present at time of VTE or within 30 days prior to VTE) were the most commonly reported (n = 18, 40.9% and n = 15, 34.09%, respectively).

Rivaroxaban is the most prescribed DOAC with 59.2% (n = 45) of patients using this agent. Apixaban and dabigatran use is also reported (n = 29; 38.2% and n = 2; 2.6% respectively). Of the 76 patients, 65 received a different anticoagulant prior to starting a DOAC. Enoxaparin and unfractionated heparin are most commonly prescribed prior to the institution of a DOAC regimen (n = 52, 80% and n = 17, 26.2%).

Conclusions: Despite lack of an FDA-approved pediatric indication, hematologists in the US are already using DOACs for children with VTE. Most pediatric patients treated with a DOAC are older than 13 years of age, although we anticipate this will change as providers develop more comfort with these drugs. Interestingly, most of these patients were started on a different anticoagulation regimen prior to starting a DOAC.

As enrollment continues, ATHN 15 will serve as a resource for pediatric hematologists to characterize the real-world use of DOACs in children. Further analysis will evaluate DOAC-specific utilization, efficacy and adverse events, including heavy menstrual bleeding.