Standard Anticoagulation May Be Overkill for Pediatric VTE

For children being treated for a provoked venous thromboembolism (VTE), a shortened course of anticoagulation struck a good balance between efficacy and safety, the small Kids-DOTT trial showed.

Six weeks of anticoagulant therapy met noninferiority criteria against the standard of 3 months in terms of both symptomatic recurrent VTE events (0.66% vs 0.70%) and clinically relevant bleeding events at 1 year (0.65% vs 0.70%), according to Neil Goldenberg, MD, PhD, of Johns Hopkins All Children’s Hospital in St. Petersburg, Florida, and colleagues, writing in JAMA.

As such, the trial provides higher-quality evidence to back guideline suggestions for a 6-week course of antithrombotic therapy in pediatric VTE as an alternative to the standard 3 months for children and adults alike.

“The findings suggest that anticoagulant therapy could be stopped sooner than currently recommended and that doing so is likely to be as safe as longer treatment. Quality of life may be improved in many children by decreasing the duration of subcutaneous injections,” said Jacques Lacroix, MD, of Université de Montréal, CHU Sainte-Justine, Quebec, and colleagues in an accompanying editorial.

According to Goldenberg and colleagues, Kids-DOTT also adds to the evidence that recurrent VTE and bleeding risks are lower than previously reported in observational studies of children receiving anticoagulation for acute VTE. “This may reflect experience gained in pediatric VTE management and improved ability to distinguish provoked from unprovoked VTE in children and young adults,” they wrote.

Kids-DOTT was a randomized trial conducted in Australia, Austria, Canada, the Netherlands, and the U.S. in 2008-2021.

Participants were 417 people younger than age 21 years with acute provoked VTE — attributed to a hospitalization-related event, trauma, or a central venous catheter — who had neither persistent antiphospholipid antibodies nor complete occlusion on repeat imaging at 6 weeks.

Patients were randomized to anticoagulant therapy, predominantly low-molecular-weight heparins, lasting 6 weeks versus the conventional 3 months. They were then followed up to 2 years with no routine surveillance imaging.

The 297 participants entered in the main per-protocol analysis had a median age of 8.3 years and were roughly split between the sexes.

Goldenberg’s group reported that adverse events, most commonly fever, reached 26% and 32% of the 6-week and 3-month anticoagulation groups, respectively.

“Should clinicians wait for the results of additional [randomized clinical trials] before changing the current guidelines? Given that the study was conducted at 42 centers in 5 countries over 13 years, it is unlikely to be repeated,” commented Lacroix and colleagues.

Nevertheless, given the small number of children with cancer or pulmonary embolism in Kids-DOTT, the investigators cautioned against applying study findings to these patients.

“Although the data reported by Goldenberg et al are compelling enough that some practitioners may want to apply them immediately, the results should be applied judiciously and not be extrapolated to patients with unprovoked VTE and older patients,” the editorialists added.

It also remains to be seen whether a shortened course of oral anticoagulants also works for pediatric VTE. Dabigatran (Pradaxa) only became the first direct oral anticoagulant approved for this indication in mid-2021.