Intrapulmonary Recombinant Factor VIIa for Diffuse Alveolar Hemorrhage in Children

Abstract

Diffuse alveolar hemorrhage (DAH) is a life-threatening pulmonary complication in patients with hematologic malignancies or autoimmune disorders, and it has a high mortality rate. The current treatment options of corticosteroids, transfusions, and immunosuppressants have been limited and largely unsuccessful, and they can be accompanied by multiple complications. Intrapulmonary administration of recombinant activated factor VII (rFVIIa) has been reported in adults, but there are scarce data on its use in children. The present article reviews our institutional experience with intrapulmonary rFVIIa for the treatment of DAH in children. The study included 6 pediatric patients with acute, bronchoscopically confirmed DAH treated between 2011 and 2013. The median age was 11 years, and patient diagnoses were as follows: acute myeloid leukemia (2 patients), myelodysplastic syndrome (1 patient), hemophagocytic lymphohistiocytosis (1 patient), T-cell lymphoblastic lymphoma (1 patient), and idiopathic pulmonary hemosiderosis (1 patient). These patients were treated with intrapulmonary rFVIIa concurrent with methylprednisolone, fresh-frozen plasma, and maintenance of the platelet count >50 000/mm3. Complete and sustained hemostasis after rFVIIa treatment and an absence of adverse events were observed in all patients. The PaO2/fraction of inspired oxygen ratio increased significantly, and rapid clinical improvements were observed. Two patients who received hematopoietic stem cell transplantation died of subsequent respiratory syncytial virus and Acinetobacter baumannii infections, but the other 4 patients exhibited rapid improvement, were successfully weaned from ventilators, and experienced long-term survival. Our findings indicate that intrapulmonary administration of rFVIIa is an effective and safe treatment option for children with DAH; however, further clinical studies are needed.