title: Recombinant human factor VIIa for alveolar hemorrhage following allogeneic stem cell transplantation.
abstract: The mortality rate of alveolar hemorrhage (AH) after allogeneic hematopoietic stem cell transplantation is greater than 60% with supportive care and high-dose steroid therapy. We performed a retrospective cohort analysis to assess the benefits and risks of recombinant human factor VIIa (rFVIIa) as a therapeutic adjunct for AH. Between 2005 and 2012, 57 episodes of AH occurred in 37 patients. Fourteen episodes (in 14 patients) were treated with steroids alone, and 43 episodes (in 23 patients) were treated with steroids and rFVIIa. The median steroid dose was 1.9 mg/kg/d (interquartile range [IQR], 0.8 to 3.5 mg/kg/d; methylprednisolone equivalents) and did not differ statistically between the 2 groups. The median rFVIIa dose was 41 μg/kg (IQR, 39 to 62 μg/kg), and a median of 3 doses (IQR, 2 to 17) was administered per episode. Concurrent infection was diagnosed in 65% of the episodes. Patients had moderately severe hypoxia (median PaO2/FiO2, 193 [IQR, 141 to 262]); 72% required mechanical ventilation, and 42% survived to extubation. The addition of rFVIIa did not alter time to resolution of AH (P = .50), duration of mechanical ventilation (P = .89), duration of oxygen supplementation (P = .55), or hospital mortality (P = .27). Four possible thrombotic events (9% of 43 episodes) occurred with rFVIIa. rFVIIa in combination with corticosteroids did not confer clear clinical advantages compared with corticosteroids alone. In patients with AH following hematopoietic stem cell transplantation, clinical factors (ie, worsening infection, multiple organ failure, or recrudescence of primary disease) may be more important than the benefit of enhanced hemostasis from rFVIIa.
authors.affiliation: Critical Care Medicine Department, Clinical Center, National Institutes of Health, Bethesda, Maryland. Electronic address: elinoffj@cc.nih.gov.
authors.forename: Jason M
authors.initials: JM
authors.lastname: Elinoff
authors.affiliation: Center for Infectious Disease Imaging, Radiology and Imaging Sciences, Clinical Center, National Institutes of Health, Bethesda, Maryland.
authors.forename: Ulas
authors.initials: U
authors.lastname: Bagci
authors.affiliation: Pharmacy Department, Clinical Center, National Institutes of Health, Bethesda, Maryland.
authors.forename: Brad
authors.initials: B
authors.lastname: Moriyama
authors.affiliation: Laboratory of Pathology, National Cancer Institute, National Institutes of Health, Bethesda, Maryland.
authors.forename: Jennifer L
authors.initials: JL
authors.lastname: Dreiling
authors.affiliation: Center for Infectious Disease Imaging, Radiology and Imaging Sciences, Clinical Center, National Institutes of Health, Bethesda, Maryland.
authors.forename: Brent
authors.initials: B
authors.lastname: Foster
authors.affiliation: Hematology Branch, National Heart, Lung and Blood Institute, National Institutes of Health, Bethesda, Maryland.
authors.forename: Nicole J
authors.initials: NJ
authors.lastname: Gormley
authors.affiliation: Experimental Transplantation and Immunology Branch, National Cancer Institute, National Institutes of Health, Bethesda, Maryland.
authors.forename: Rachel B
authors.initials: RB
authors.lastname: Salit
authors.affiliation: Critical Care Medicine Department, Clinical Center, National Institutes of Health, Bethesda, Maryland.
authors.forename: Rongman
authors.initials: R
authors.lastname: Cai
authors.affiliation: Critical Care Medicine Department, Clinical Center, National Institutes of Health, Bethesda, Maryland.
authors.forename: Junfeng
authors.initials: J
authors.lastname: Sun
authors.affiliation: Laboratory for Informatics Development, Biomedical Translational Research Information System, Clinical Center, National Institutes of Health, Bethesda, Maryland.
authors.forename: Andrea
authors.initials: A
authors.lastname: Beri
authors.affiliation: Critical Care Medicine Department, Clinical Center, National Institutes of Health, Bethesda, Maryland.
authors.forename: Debra J
authors.initials: DJ
authors.lastname: Reda
authors.affiliation: Critical Care Medicine Department, Clinical Center, National Institutes of Health, Bethesda, Maryland.
authors.forename: Farhad
authors.initials: F
authors.lastname: Fakhrejahani
authors.affiliation: Hematology Branch, National Heart, Lung and Blood Institute, National Institutes of Health, Bethesda, Maryland.
authors.forename: Minoo
authors.initials: M
authors.lastname: Battiwalla
authors.affiliation: Pediatric Oncology Branch, National Cancer Institute, National Institutes of Health, Bethesda, Maryland.
authors.forename: Kristin
authors.initials: K
authors.lastname: Baird
authors.affiliation: Laboratory of Clinical Infectious Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland.
authors.forename: Jennifer M
authors.initials: JM
authors.lastname: Cuellar-Rodriguez
authors.affiliation: Laboratory of Host Defenses, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland.
authors.forename: Elizabeth M
authors.initials: EM
authors.lastname: Kang
authors.affiliation: Experimental Transplantation and Immunology Branch, National Cancer Institute, National Institutes of Health, Bethesda, Maryland.
authors.forename: Stephen Z
authors.initials: SZ
authors.lastname: Pavletic
authors.affiliation: Experimental Transplantation and Immunology Branch, National Cancer Institute, National Institutes of Health, Bethesda, Maryland.
authors.forename: Dan H
authors.initials: DH
authors.lastname: Fowler
authors.affiliation: Hematology Branch, National Heart, Lung and Blood Institute, National Institutes of Health, Bethesda, Maryland.
authors.forename: A
authors.initials: A
authors.lastname: John Barrett
authors.affiliation: Hematology Service, Department of Laboratory Medicine, Clinical Center, National Institutes of Health, Bethesda, Maryland.
authors.forename: Jay N
authors.initials: JN
authors.lastname: Lozier
authors.affiliation: Laboratory of Pathology, National Cancer Institute, National Institutes of Health, Bethesda, Maryland.
authors.forename: David E
authors.initials: DE
authors.lastname: Kleiner
authors.affiliation: Center for Infectious Disease Imaging, Radiology and Imaging Sciences, Clinical Center, National Institutes of Health, Bethesda, Maryland.
authors.forename: Daniel J
authors.initials: DJ
authors.lastname: Mollura
authors.affiliation: Hematology Branch, National Heart, Lung and Blood Institute, National Institutes of Health, Bethesda, Maryland.
authors.forename: Richard W
authors.initials: RW
authors.lastname: Childs
authors.affiliation: Critical Care Medicine Department, Clinical Center, National Institutes of Health, Bethesda, Maryland.
authors.forename: Anthony F
authors.initials: AF
authors.lastname: Suffredini
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D002648:Child; D015331:Cohort Studies; D015942:Factor VIIa / Q000627:therapeutic use*; D005260:Female; D018380:Hematopoietic Stem Cell Transplantation / Q000009:adverse effects*; D006470:Hemorrhage / Q000188:drug therapy* / Q000209:etiology*; D006801:Humans; D008171:Lung Diseases / Q000188:drug therapy* / Q000209:etiology / Q000473:pathology; D008297:Male; D008875:Middle Aged; D011650:Pulmonary Alveoli / Q000473:pathology; D011994:Recombinant Proteins / Q000627:therapeutic use; D012189:Retrospective Studies; D019172:Transplantation Conditioning / Q000009:adverse effects*; D014184:Transplantation, Homologous; D055815:Young Adult
chemical_list: D011994:Recombinant Proteins; C103587:recombinant FVIIa; D015942:Factor VIIa
keywords: Diffuse alveolar hemorrhage; Glucocorticoids; Hematopoietic stem cell transplantation; Recombinant human factor VIIa