The FDA has approved an expanded indication for Grifols' antithrombin III (human) (THROMBATE III) to include pediatric patients diagnosed with hereditary antithrombin deficiency (hATd), marking a significant milestone in treating this rare blood clotting disorder. With this label update announced on November 18, 2025, antithrombin III becomes the first and only antithrombin concentrate (ATc) approved for both adults and pediatric patients with hATd.
The approval was supported by extrapolation of data from two clinical studies in adult patients, which concluded that ATc can be "safely and effectively used in pediatric patients with hATd," according to Grifols. This regulatory decision addresses a critical unmet medical need in pediatric care for a disorder that carries substantial thrombotic risk.
Addressing High-Risk Thrombotic Disorder
Hereditary antithrombin deficiency is a frequently undiagnosed blood clotting disorder that may affect up to 700,000 people in the United States. Patients living with the disease face a higher-than-average risk of developing abnormal blood clots, with hATd having one of the highest thrombotic risks of all inherited thrombophilias. According to Grifols, 85% of patients with hATd will experience at least one thrombotic episode by age 50.
"This label expansion helps close a long-standing gap in the treatment of pediatric patients with hereditary antithrombin deficiency," said George M. Rodgers, III, MD, PhD, professor of Medicine, Division of Hematology and Hematologic Malignancies, University of Utah School of Medicine. "It gives clinicians added confidence that ATc can be appropriately used in children."
Clinical Evidence Supporting Approval
The expanded indication is supported by clinical trial data demonstrating the efficacy of antithrombin III in patients with hATd for treatment and prevention of thromboembolism before, during, and after surgery and childbirth. In a prospective open-label clinical trial, 21 participants were administered THROMBATE III for 16 prophylaxis events and 10 for treatment of thrombosis, with 2 patients receiving treatment for both prophylaxis and thrombosis management.
Notably, none of the 13 patients with hATd and histories of thromboembolism treated prophylactically on 16 separate occasions with THROMBATE III for high thrombotic risk situations—including 11 surgical procedures and 5 pregnancies and/or deliveries—developed thrombotic complications. Among 10 patients with hATd treated with both THROMBATE III and heparin for major thrombotic or thromboembolic complications, including 4 with thrombosis during their first trimester of pregnancy, 9 recovered with no additional thromboses or extension of existing thrombosis.
Dosing and Administration
The dose is individualized to achieve an antithrombin level of 80% to 120% of normal human plasma, with the rate of administration adapted based on individual patient responses. The full dose is typically given over 10- to 20-minute durations, and there are no known contraindications to the treatment.
Safety Profile and Considerations
In clinical studies, the most common adverse reactions (≥5%) included dizziness, chest discomfort, nausea, dysgeusia, and pain (cramps). Most adverse events were considered mild or moderate, with no serious adverse events reported in the clinical trials.
Healthcare providers should be aware that the anticoagulant effect of heparin is increased when used with antithrombin III in patients with hereditary AT deficiency, potentially requiring heparin or low-molecular-weight heparin dose reductions to avoid bleeding. Additionally, because antithrombin III is derived from human plasma, it may pose a risk of transmitting infectious agents, including viruses and theoretically the Creutzfeldt-Jakob disease agent.
"Expanding the indication to include pediatric patients provides a new option for children and families facing hereditary antithrombin deficiency," said Roland Wandeler, president of Grifols Biopharma, emphasizing the significance of this approval for the pediatric patient population previously lacking approved treatment options.
