title: Inhalational use of antithrombotics in humans: Review of the literature.
abstract: BACKGROUND
  Off label use of anticoagulants is common. The association between fibrin deposition in the lungs and primary lung disease, injury or prematurity affords a strong theoretical basis for the potential benefit of antithrombotic therapies administered directly to the lung tissue. This review offers a critical appraisal of current evidence related to the inhalational administration of antithrombotic therapy in humans.
  
  
  METHODS
  An interrogation of 2 databases across a 13 year period of time was undertaken using key words selected a priori. Identified publications were categorized according to the following themes: 1. Inhaled antithrombotic therapy in healthy subjects 2. Inhaled antithrombotic therapy for vascular thromboprophylaxis 3. Inhaled antithrombotic therapy in smoke inhalation and lung injury 4. Inhaled antithrombotic therapy in asthma or allergy 5. Inhaled antithrombotic therapy for plastic bronchitis post-Fontan surgery 6. Inhaled antithrombotic therapy for other indications.
  
  
  RESULTS
  33 articles were identified consistent with the inclusion criteria developed for this review. Unfractionated heparin, LMWH, activated protein C and thrombolytic agents have been administered via the respiratory track, with asthma and smoke inhalation/lung injury being the most frequently investigated clinical scenarios described. All studies reported had significant methodological limitations.
  
  
  CONCLUSIONS
  The safety and clinical utility of inhaled antithrombotic therapies have not been adequately investigated to support the generation of any firm evidence. This review highlights where inhaled antithrombotic therapies have shown promise and importantly, the further research required to confirm mechanism of action and a definitive risk: benefit profile.
authors.affiliation: Department of Paediatrics, The University of Melbourne, Australia.
authors.forename: K
authors.initials: K
authors.lastname: Monagle
authors.affiliation: Department of Paediatrics, The University of Melbourne, Australia; Clinical Haematology Department, The Royal Children's Hospital, Australia.
authors.forename: A
authors.initials: A
authors.lastname: Ryan
authors.affiliation: Department of Paediatrics, The University of Melbourne, Australia; Haematology Research Group, Murdoch Childrens Research Institute, Australia.
authors.forename: M
authors.initials: M
authors.lastname: Hepponstall
authors.affiliation: Department of Paediatrics, The University of Melbourne, Australia.
authors.forename: E
authors.initials: E
authors.lastname: Mertyn
authors.affiliation: Department of Paediatrics, The University of Melbourne, Australia; Haematology Research Group, Murdoch Childrens Research Institute, Australia; Clinical Haematology Department, The Royal Children's Hospital, Australia.
authors.forename: P
authors.initials: P
authors.lastname: Monagle
authors.affiliation: Department of Paediatrics, The University of Melbourne, Australia; Haematology Research Group, Murdoch Childrens Research Institute, Australia.
authors.forename: V
authors.initials: V
authors.lastname: Ignjatovic
authors.affiliation: Department of Paediatrics, The University of Melbourne, Australia; Haematology Research Group, Murdoch Childrens Research Institute, Australia; Clinical Haematology Department, The Royal Children's Hospital, Australia; Department of Nursing, The University of Melbourne, Australia; Nursing Research Department, The Royal Children's Hospital, Australia. Electronic address: Fiona.newall@rch.org.au.
authors.forename: F
authors.initials: F
authors.lastname: Newall
mesh_terms: D000280:Administration, Inhalation; D005343:Fibrinolytic Agents / Q000008:administration & dosage* / Q000009:adverse effects; D006493:Heparin / Q000008:administration & dosage; D006495:Heparin, Low-Molecular-Weight / Q000008:administration & dosage; D006801:Humans; D020246:Venous Thrombosis / Q000517:prevention & control
chemical_list: D005343:Fibrinolytic Agents; D006495:Heparin, Low-Molecular-Weight; D006493:Heparin
keywords: Antithrombotic therapy; Inhaled; Thrombolytic therapy