{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,1]],"date-time":"2026-08-01T10:38:09Z","timestamp":1785580689121,"version":"3.56.0"},"reference-count":25,"publisher":"American Academy of Pediatrics (AAP)","issue":"1","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2015,1,1]]},"abstract":"<jats:p>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 &amp;gt;50\u2009000\/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.<\/jats:p>","DOI":"10.1542\/peds.2014-1782","type":"journal-article","created":{"date-parts":[[2014,12,30]],"date-time":"2014-12-30T01:30:05Z","timestamp":1419903005000},"page":"e216-e220","source":"Crossref","is-referenced-by-count":36,"title":["Intrapulmonary Recombinant Factor VIIa for Diffuse Alveolar Hemorrhage in Children"],"prefix":"10.1542","volume":"135","author":[{"given":"Jeong A.","family":"Park","sequence":"first","affiliation":[{"name":"Department of Pediatrics, Haeundae-Paik Hospital, Inje University College of Medicine, Busan, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Byoung-Ju","family":"Kim","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Haeundae-Paik Hospital, Inje University College of Medicine, Busan, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"417","published-online":{"date-parts":[[2015,1,1]]},"reference":[{"issue":"4","key":"2021120907193751000_B1","doi-asserted-by":"crossref","first-page":"1014","DOI":"10.1097\/00003246-200004000-00017","article-title":"Outcome of bone marrow transplantation patients requiring mechanical ventilation.","volume":"28","author":"Huaringa","year":"2000","journal-title":"Crit Care Med"},{"issue":"5","key":"2021120907193751000_B2","doi-asserted-by":"crossref","first-page":"539","DOI":"10.1038\/sj.bmt.1702546","article-title":"Increasing incidence of diffuse alveolar hemorrhage following allogeneic bone marrow transplantation: cryptic etiology and uncertain therapy.","volume":"26","author":"Lewis","year":"2000","journal-title":"Bone Marrow Transplant"},{"issue":"4","key":"2021120907193751000_B3","first-page":"1006","article-title":"Diffuse alveolar hemorrhage in allogeneic bone marrow transplantation. A postmortem study.","volume":"151","author":"Agust\u00ed","year":"1995","journal-title":"Am J Respir Crit Care Med"},{"key":"2021120907193751000_B4","first-page":"37","article-title":"Local pulmonary administration of factor VIIa (rFVIIa) in diffuse alveolar hemorrhage (DAH)\u2014a review of a new treatment paradigm.","volume":"6","author":"Heslet","year":"2012","journal-title":"Biologics"},{"issue":"4","key":"2021120907193751000_B5","doi-asserted-by":"crossref","first-page":"411","DOI":"10.1002\/ppul.21178","article-title":"Bronchoscopic instillation of activated recombinant factor VII to treat diffuse alveolar hemorrhage in a child.","volume":"45","author":"Colin","year":"2010","journal-title":"Pediatr Pulmonol"},{"issue":"3","key":"2021120907193751000_B6","doi-asserted-by":"crossref","first-page":"257","DOI":"10.1002\/mpo.2950090309","article-title":"The cytosine arabinoside (Ara-C) syndrome.","volume":"9","author":"Castleberry","year":"1981","journal-title":"Med Pediatr Oncol"},{"issue":"5","key":"2021120907193751000_B7","doi-asserted-by":"crossref","first-page":"1079","DOI":"10.1002\/1097-0142(19900301)65:5<1079::AID-CNCR2820650506>3.0.CO;2-K","article-title":"Fatal pulmonary failure complicating high-dose cytosine arabinoside therapy in acute leukemia.","volume":"65","author":"Andersson","year":"1990","journal-title":"Cancer"},{"issue":"6","key":"2021120907193751000_B8","doi-asserted-by":"crossref","first-page":"R177","DOI":"10.1186\/cc5132","article-title":"Successful pulmonary administration of activated recombinant factor VII in diffuse alveolar hemorrhage.","volume":"10","author":"Heslet","year":"2006","journal-title":"Crit Care"},{"issue":"8","key":"2021120907193751000_B9","doi-asserted-by":"crossref","first-page":"879","DOI":"10.1038\/sj.bmt.1701995","article-title":"High-dose corticosteroid therapy for diffuse alveolar hemorrhage in allogeneic bone marrow stem cell transplant recipients.","volume":"24","author":"Raptis","year":"1999","journal-title":"Bone Marrow Transplant"},{"issue":"5","key":"2021120907193751000_B10","doi-asserted-by":"crossref","first-page":"965","DOI":"10.1542\/peds.109.5.965","article-title":"Diffuse alveolar hemorrhage in pediatric hematopoietic cell transplant patients.","volume":"109","author":"Heggen","year":"2002","journal-title":"Pediatrics"},{"issue":"4","key":"2021120907193751000_B11","doi-asserted-by":"crossref","first-page":"269","DOI":"10.1097\/SMJ.0b013e3182126d3b","article-title":"Diffuse alveolar hemorrhage.","volume":"104","author":"Newsome","year":"2011","journal-title":"South Med J"},{"issue":"3","key":"2021120907193751000_B12","doi-asserted-by":"crossref","first-page":"314","DOI":"10.1097\/MOP.0b013e3280dd8c4a","article-title":"Diffuse alveolar hemorrhage syndromes in children.","volume":"19","author":"Susarla","year":"2007","journal-title":"Curr Opin Pediatr"},{"issue":"12","key":"2021120907193751000_B13","doi-asserted-by":"crossref","first-page":"975","DOI":"10.1038\/sj.bmt.1703731","article-title":"Treatment of diffuse alveolar hemorrhage after allogeneic bone marrow transplant with recombinant factor VIIa.","volume":"30","author":"Hicks","year":"2002","journal-title":"Bone Marrow Transplant"},{"issue":"10","key":"2021120907193751000_B14","doi-asserted-by":"crossref","first-page":"1038","DOI":"10.1016\/j.bbmt.2006.06.002","article-title":"Diffuse alveolar hemorrhage and infection-associated alveolar hemorrhage following hematopoietic stem cell transplantation: related and high-risk clinical syndromes.","volume":"12","author":"Majhail","year":"2006","journal-title":"Biol Blood Marrow Transplant"},{"issue":"5","key":"2021120907193751000_B15","doi-asserted-by":"crossref","first-page":"641","DOI":"10.1164\/rccm.200112-141CC","article-title":"Diffuse alveolar hemorrhage in hematopoietic stem cell transplant recipients.","volume":"166","author":"Afessa","year":"2002","journal-title":"Am J Respir Crit Care Med"},{"issue":"6","key":"2021120907193751000_B16","doi-asserted-by":"crossref","first-page":"2400","DOI":"10.1016\/S0012-3692(15)31709-8","article-title":"Diffuse alveolar hemorrhage after allogeneic hematopoietic stem-cell transplantation: treatment with recombinant factor VIIa.","volume":"124","author":"Pastores","year":"2003","journal-title":"Chest"},{"issue":"5","key":"2021120907193751000_B17","doi-asserted-by":"crossref","first-page":"403","DOI":"10.1038\/sj.bmt.1703381","article-title":"Acquired factor VII deficiency in hematopoietic stem cell transplant recipients.","volume":"29","author":"Toor","year":"2002","journal-title":"Bone Marrow Transplant"},{"issue":"3","key":"2021120907193751000_B18","doi-asserted-by":"crossref","first-page":"1066","DOI":"10.1542\/peds.2008-1685","article-title":"Pediatric off-label use of recombinant factor VIIa.","volume":"123","author":"Alten","year":"2009","journal-title":"Pediatrics"},{"issue":"19","key":"2021120907193751000_B19","doi-asserted-by":"crossref","first-page":"1791","DOI":"10.1056\/NEJMoa1006221","article-title":"Safety of recombinant activated factor VII in randomized clinical trials.","volume":"363","author":"Levi","year":"2010","journal-title":"N Engl J Med"},{"issue":"2","key":"2021120907193751000_B20","first-page":"CD005011","article-title":"Recombinant factor VIIa for the prevention and treatment of bleeding in patients without haemophilia.","author":"Stanworth","year":"2007","journal-title":"Cochrane Database Syst Rev"},{"issue":"4","key":"2021120907193751000_B21","doi-asserted-by":"crossref","first-page":"301","DOI":"10.1080\/08880010802016904","article-title":"Single-center experience: use of recombinant factor VIIa for acute life-threatening bleeding in children without congenital hemorrhagic disorder.","volume":"25","author":"Yilmaz","year":"2008","journal-title":"Pediatr Hematol Oncol"},{"issue":"6","key":"2021120907193751000_B22","doi-asserted-by":"crossref","first-page":"919","DOI":"10.1111\/j.1537-2995.2006.00824.x","article-title":"Recombinant factor VIIa in patients with coagulopathy secondary to anticoagulant therapy, cirrhosis, or severe traumatic injury: review of safety profile.","volume":"46","author":"Levy","year":"2006","journal-title":"Transfusion"},{"issue":"1","key":"2021120907193751000_B23","doi-asserted-by":"crossref","first-page":"S105","DOI":"10.1053\/j.seminhematol.2005.11.025","article-title":"Mechanism of action of recombinant activated factor VII: an update.","volume":"43","author":"Hedner","year":"2006","journal-title":"Semin Hematol"},{"issue":"6","key":"2021120907193751000_B24","doi-asserted-by":"crossref","first-page":"911","DOI":"10.1097\/01.TP.0000136988.38919.FB","article-title":"Impact of thrombophilic gene mutations and graft-versus-host disease on thromboembolic complications after allogeneic hematopoietic stem-cell transplantation.","volume":"78","author":"Pihusch","year":"2004","journal-title":"Transplantation"},{"issue":"3","key":"2021120907193751000_B25","doi-asserted-by":"crossref","first-page":"131","DOI":"10.1046\/j.1423-0410.1999.7730131.x","article-title":"Use of recombinant, activated factor VII in the treatment of congenital factor VII deficiencies.","volume":"77","author":"Mariani","year":"1999","journal-title":"Vox Sang"}],"container-title":["Pediatrics"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/publications.aap.org\/pediatrics\/article-pdf\/135\/1\/e216\/901036\/peds_2014-1782.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/publications.aap.org\/pediatrics\/article-pdf\/135\/1\/e216\/901036\/peds_2014-1782.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2021,12,10]],"date-time":"2021-12-10T01:56:56Z","timestamp":1639101416000},"score":1,"resource":{"primary":{"URL":"https:\/\/publications.aap.org\/pediatrics\/article\/135\/1\/e216\/52813\/Intrapulmonary-Recombinant-Factor-VIIa-for-Diffuse"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2015,1,1]]},"references-count":25,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2015,1,1]]},"published-print":{"date-parts":[[2015,1,1]]}},"URL":"https:\/\/doi.org\/10.1542\/peds.2014-1782","relation":{},"ISSN":["0031-4005","1098-4275"],"issn-type":[{"value":"0031-4005","type":"print"},{"value":"1098-4275","type":"electronic"}],"subject":[],"published":{"date-parts":[[2015,1,1]]}}}