Research and Development, Ikaria, Inc,, 6 Route 173, Clinton, NJ 08809 USA.
Thromb J. 2012 Jan 9;10:1. doi: 10.1186/1477-9560-10-1.
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.
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.
Inhaled NO, when administered with heparin, exhibited no significant additive effects on ACT, PT, aPTT, bleeding time or platelet aggregation.
一氧化氮（NO）对止血的影响已在各种研究环境中进行了研究，但关于吸入 NO 对出血和血小板功能的影响的数据存在冲突。目前尚不清楚吸入 NO 是否会在与影响止血的药物联合使用时产生影响。本试验评估了吸入 NO 在肝素存在的情况下对止血的影响，并使用阿司匹林作为阳性对照。
患者/方法：12 名健康成年男性参与了一项单中心、随机、单盲、四交叉试验。受试者接受 80 ppm 的 NO 或医用空气（安慰剂）吸入 30 分钟，同时注射安慰剂或肝素。阿司匹林胶囊用作阳性对照。在治疗前和治疗后间隔测量止血参数。
仅在接受肝素的组中，激活凝血时间（ACT）、凝血酶原时间（PT）和活化部分凝血活酶时间（aPTT）增加。接受吸入 NO 的肝素组的 ACT 曲线下面积被判断为与接受医用空气的组相当，无论是在 0 至 4 小时（比值：1.00；90%置信区间，0.90-1.11）还是 0 至 24 小时的时间间隔（比值：1.01；90%置信区间，0.92-1.12）。仅在阿司匹林组观察到出血时间和血小板聚集的变化。在任何组中，血红蛋白、红细胞计数或血细胞比容均未观察到临床意义上的变化。
当与肝素联合使用时，吸入 NO 对 ACT、PT、aPTT、出血时间或血小板聚集没有明显的附加作用。
