Related Experiment Video
Updated: May 26, 2026

A Novel Inhalation Mask System to Deliver High Concentrations of Nitric Oxide Gas in Spontaneously Breathing Subjects
Published on: May 4, 2021
Effects of inhaled nitric oxide on hemostasis in healthy adults treated with heparin: a randomized, controlled,
Brahm Goldstein1, James Baldassarre, Joseph N Young
1Research and Development, Ikaria, Inc,, 6 Route 173, Clinton, NJ 08809 USA. brahm.goldstein@ikaria.com.
Background:
Effects of nitric oxide (NO) on hemostasis have been studied in various investigational settings, but data regarding inhaled NO on bleeding and platelet function are conflicting. It is not known if inhaled NO has an effect when administered with drugs that influence hemostasis. This trial evaluated effects of inhaled NO on hemostasis in the presence of heparin using aspirin as a positive control.
Patients/Methods:
Twelve healthy adult males were enrolled in a single-center, randomized, single-blind, four-way crossover trial. Subjects received 80 ppm NO or medical air (placebo) inhalation for 30 min with simultaneous injection of placebo or heparin. Aspirin capsules were used as a positive control. Parameters of hemostasis were measured before treatment and at post-treatment intervals.
Results:
Activated clotting time (ACT), prothrombin time (PT) and activated partial thromboplastin time (aPTT) increased only in groups that received heparin. Areas under the curve for ACT in heparin groups receiving inhaled NO were judged to be equivalent to those receiving medical air for both 0- to 4-h (ratio: 1.00; 90% CI, 0.90-1.11) and 0- to 24-h time intervals (ratio: 1.01; 90% CI, 0.92-1.12). Changes in bleeding time and platelet aggregation were observed only in aspirin groups. No clinically significant changes in hemoglobin, red blood cell counts or haematocrit were observed in any group.
Conclusions:
Inhaled NO, when administered with heparin, exhibited no significant additive effects on ACT, PT, aPTT, bleeding time or platelet aggregation.
Related Concept Videos
Nitric Oxide Signaling Pathway
Anticoagulant Drugs: Low-Molecular-Weight Heparins
Antianginal Drugs: Nitrates and β-Blockers
Organic nitrates, such as nitroglycerin, play a pivotal role. Once metabolized, they liberate nitric oxide, a molecular marvel. Nitric oxide triggers guanylyl cyclase and augments cGMP production. This biochemical cascade orchestrates the relaxation of vascular smooth muscles, ushering in vasodilation and enhancing coronary blood flow. Administered...
Treatment for Pulmonary Arterial Hypertension: Prostacyclin Receptor Agonists
These agonists bind to the IPR receptor situated on the plasma membrane of the pulmonary artery smooth muscle cells. This binding triggers a cascade of reactions known as the GS-AC-cAMP-PKA pathway. This pathway results in the relaxation of smooth muscle...
Antihypertensive Drugs: Vasodilators
Treatment for Pulmonary Arterial Hypertension: Phosphodiesterase Inhibitors
Among the PDE5 inhibitors, sildenafil (Revatio) stands out as a competitive and selective inhibitor. It operates by elevating cellular levels of cGMP and augmenting signaling through the cGMP-PKG pathway, promoting vasodilation. Upon oral...

