324 - Challenges in the Management of Factor VII Deficiency in a Pediatric Patient Complicated by Presence of Inhibitor

Poster Number: 324

Ariane Moffett, Sanford Children's Hospital, Sioux Falls, SD, United States; Brianna Murphy, Sanford Children's Hospital, Sioux Falls, SD, United States

Background: Among the rare inherited bleeding disorders, factor VII deficiency is the most common. The incidence of a severe homozygous deficiency is 1 in 300,000-500,000 people worldwide. There is wide variability in penetrance and bleeding phenotype, often making management difficult. Current treatments involve replacement therapy with recombinant Factor VII, plasma or FFP, however these products remain challenging due to the short half-life and availability for home prophylactic regimens. 

Objective:  (1) To discuss the management of a severe factor VII deficiency in a growing child given the limitations of current treatments. Recombinant factor VII has a short half-life, complicating prophylactic infusion schedules. (2) To discuss approaches in eradicating inhibitors in patients with factor VII deficiency.

Design/Methods: On initial diagnosis, the patient was started on 30 mcg/kg of daily NovoSeven infusions Monday through Friday. She was maintained on this regimen for three months, until she developed a spontaneous intracranial hemorrhage. Her NovoSeven dosing was increased to 90mcg/kg every 12 hours as she was unable to be safely weaned to every 24 hours due to oozing and increasing INR (international normalized ratio). This prophylactic regimen was complicated by multiple central line infections, requiring two central line removals. At 18 months of age, she was incidentally found to have a spontaneous subdural hematoma and a knee joint bleed with good compliance to her twice daily NovoSeven infusions. Mixing studies were obtained and were indicative of an inhibitor to Factor VII. She was treated with high dose steroids followed by Rituximab and finally cyclophosphamide and IVIG with no improvement in her inhibitor status. 

Results: Since the patient has been unable to clear the inhibitor and INR levels continue to be abnormal, she was switched to Sevenfact in place of NovoSeven. Conclusion(s): Currently, there are published case studies that share treatment regimens for factor VII prophylaxis, such as the Seven Treatment Evaluation Registry. However, there are currently no published guidelines regarding prophylaxis management for patients with severe bleeding phenotypes. Furthermore, there are also no guidelines that address inhibitor management for factor VII deficiency. Patients, like ours, who develop inhibitors refractory to treatment are at a greater risk of mortality due to life threatening bleeds. Therefore, further research is needed to develop management guidelines for patients with severe factor VII deficiency in need of prophylactic therapy and treatment of inhibitors.