Effect of inhaled heparin on lung function and coagulation in healthy volunteers

The aim of the present study was to investigate the safety of increasing doses of a well-defined lower respiratory tract (LRT) dose of inhaled heparin with regard to pulmonary function and coagulation. Ten volunteers inhaled heparin from Sidestream jet nebulizers loaded with 100,000, 200,000, 300,000 or 400,000 International Units (IU) of heparin. Lung function, antifactor (anti)-Xa, activated partial thromboplastin time (APTT), tissue factor pathway inhibitor (TFPI), whole blood clotting time, platelets, von Willebrand factor, and C-reactive protein were determined before and 1, 3, 6, and 24 h after inhalation. The highest LRT dose was 32,000 IU heparin. Inhaled heparin did not affect pulmonary function. The area under the curve of the anti-Xa activity increased with increasing doses of heparin (p=0.005), but remained unchanged for all other variables. Peak anti-Xa activity was 0.113 IU x mL(-1) 6 h after inhalation of 400,000 IU heparin. When compared to baseline values: anti-Xa increased after 200,000 (p=0.03), 300,000 (p=0.004), and 400,000 IU (p=0.002) heparin; APTT increased to a maximum of 1.03 6 h after inhalation of 400,000 IU heparin (p=0.05); TFPI increased after 100,000 (p=0.01), 200,000 (p=0.01), 300,000 (p=0.006) and 400,000 IU (p<0.001). Inhaled heparin delivery of 32,000 International Units to the lower respiratory tract can safely be inhaled for clinical or research purposes.