Inhalational use of antithrombotics in humans: Review of the literature

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.

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.

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.

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.