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Effects of inhaled nitric oxide on hemostasis in healthy adults treated with heparin: a randomized, controlled, blinded crossover study.

Goldstein B, Baldassarre J, Young JN - Thromb J (2012)

Bottom Line: 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.Inhaled NO, when administered with heparin, exhibited no significant additive effects on ACT, PT, aPTT, bleeding time or platelet aggregation.

View Article: PubMed Central - HTML - PubMed

Affiliation: Research and Development, Ikaria, Inc,, 6 Route 173, Clinton, NJ 08809 USA. brahm.goldstein@ikaria.com.

ABSTRACT

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.

No MeSH data available.


Related in: MedlinePlus

cGMP levels before and at various time points after treatment. HNP, heparin injection + nitric oxide inhalation + placebo capsules; HPP, heparin injection + placebo inhalation + placebo capsules; PNP, placebo injection + nitric oxide inhalation + placebo capsules; PPA, placebo injection + placebo inhalation + aspirin capsules.
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Figure 6: cGMP levels before and at various time points after treatment. HNP, heparin injection + nitric oxide inhalation + placebo capsules; HPP, heparin injection + placebo inhalation + placebo capsules; PNP, placebo injection + nitric oxide inhalation + placebo capsules; PPA, placebo injection + placebo inhalation + aspirin capsules.

Mentions: As mentioned previously, 6 patients had cGMP estimations conducted during Treatment Period 3 (Figure 6); these measurements were performed as a marker of biological activity and were considered non-pivotal data. Among the 6 patients, 4 had cGMP levels that remained relatively stable. Two patients (PNP and HNP) had cGMP elevations that peaked at 5 and 15 min, respectively, and then returned to near-baseline levels by the end of the treatment period (min 45-60).


Effects of inhaled nitric oxide on hemostasis in healthy adults treated with heparin: a randomized, controlled, blinded crossover study.

Goldstein B, Baldassarre J, Young JN - Thromb J (2012)

cGMP levels before and at various time points after treatment. HNP, heparin injection + nitric oxide inhalation + placebo capsules; HPP, heparin injection + placebo inhalation + placebo capsules; PNP, placebo injection + nitric oxide inhalation + placebo capsules; PPA, placebo injection + placebo inhalation + aspirin capsules.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC3275474&req=5

Figure 6: cGMP levels before and at various time points after treatment. HNP, heparin injection + nitric oxide inhalation + placebo capsules; HPP, heparin injection + placebo inhalation + placebo capsules; PNP, placebo injection + nitric oxide inhalation + placebo capsules; PPA, placebo injection + placebo inhalation + aspirin capsules.
Mentions: As mentioned previously, 6 patients had cGMP estimations conducted during Treatment Period 3 (Figure 6); these measurements were performed as a marker of biological activity and were considered non-pivotal data. Among the 6 patients, 4 had cGMP levels that remained relatively stable. Two patients (PNP and HNP) had cGMP elevations that peaked at 5 and 15 min, respectively, and then returned to near-baseline levels by the end of the treatment period (min 45-60).

Bottom Line: 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.Inhaled NO, when administered with heparin, exhibited no significant additive effects on ACT, PT, aPTT, bleeding time or platelet aggregation.

View Article: PubMed Central - HTML - PubMed

Affiliation: Research and Development, Ikaria, Inc,, 6 Route 173, Clinton, NJ 08809 USA. brahm.goldstein@ikaria.com.

ABSTRACT

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.

No MeSH data available.


Related in: MedlinePlus