title: Pilot trial of a novel two-step therapy protocol using nebulized tranexamic acid and recombinant factor VIIa in children with intractable diffuse alveolar hemorrhage.
abstract: OBJECTIVE
  Diffuse alveolar hemorrhage (DAH) is a life threatening condition with very limited, often unsuccessful, therapeutic options. This study aimed at exploring the feasibility and efficacy of nebulized tranexamic acid TXA (n-TXA) and nebulized recombinant factor VIIa (n-rFVIIa) when used in a two-step therapy protocol in children with intractable DAH in a pediatric intensive care unit.
  
  
  METHODS
  In a prospective trial, n-TXA (250 mg/dose for children < 25 kg and 500 mg/dose for children > 25 kg) was administered to 18 children (median age [interquartile range]; 24.0 months [11.3, 58.5]) with intractable DAH. N-rFVIIa (35 micro g/kg/dose for children < 25 kg, and 50 micro g/kg/dose for children > 25 kg) was added if no or minimal response was seen after 3 to 4 doses (18 to 24 hours) of n-TXA.
  
  
  RESULTS
  DAH was stopped in 10 (55.6%) children with n-TXA alone within 24 hours of therapy. Documented concomitant respiratory infection showed a significant negative association with response to n-TXA in a step.wise regression analysis (OR=0.06; 95% CI=0.01-0.74). In the other 8 (44.4%) children, n-rFVIIa was added due to n-TXA failure. Six (75.0%) showed complete cessation of DAH, while two children failed to respond with the addition of n-rFVIIa (25.0%). None of the children who responded to therapy showed recurrence of DAH after therapy termination. No complications related to therapy were recorded.
  
  
  CONCLUSIONS
  n-TXA and n-rFVIIa were effective and safe when used in a two-step-therapy protocol to control intractable DAH in pediatric patients in intensive care settings. This therapy modality warrants further exploration through larger multicenter clinical trials.
authors.affiliation: Hind Bafaqih, Consultant Pediatric Intensive Care Medicine, Pediatric Intensive Care Unit, Prince Sultan Military Hospital, Riyadh, Saudi Arabia, M: 966555558218, hbafagih13@gmail.com.
authors.forename: Hind
authors.initials: H
authors.lastname: Bafaqih
authors.forename: May
authors.initials: M
authors.lastname: Chehab
authors.forename: Suliman
authors.initials: S
authors.lastname: Almohaimeed
authors.forename: Farah
authors.initials: F
authors.lastname: Thabet
authors.forename: Abdulrahman
authors.initials: A
authors.lastname: Alhejaily
authors.forename: Mohammed
authors.initials: M
authors.lastname: AlShahrani
authors.forename: Mohammed A
authors.initials: MA
authors.lastname: Zolaly
authors.forename: Abeer A
authors.initials: AA
authors.lastname: Abdelmoneim
authors.forename: Ehab S
authors.initials: ES
authors.lastname: Abd
mesh_terms: D000933:Antifibrinolytic Agents / Q000008:administration & dosage*; D002675:Child, Preschool; D004359:Drug Therapy, Combination / Q000379:methods; D015942:Factor VIIa / Q000008:administration & dosage*; D005240:Feasibility Studies; D005260:Female; D006470:Hemorrhage / Q000188:drug therapy*; D006801:Humans; D007223:Infant; D015278:Intensive Care Units, Pediatric; D008171:Lung Diseases / Q000188:drug therapy*; D008297:Male; D009330:Nebulizers and Vaporizers; D010865:Pilot Projects; D011446:Prospective Studies; D011650:Pulmonary Alveoli; D011994:Recombinant Proteins / Q000008:administration & dosage; D014148:Tranexamic Acid / Q000008:administration & dosage*; D016896:Treatment Outcome
chemical_list: D000933:Antifibrinolytic Agents; D011994:Recombinant Proteins; D014148:Tranexamic Acid; C103587:recombinant FVIIa; D015942:Factor VIIa