Martini Wenjun Z, Rodriguez Cassandra M, Deguzman Rodolfo, Guerra Jessica B, Martin Angela K, Pusateri Anthony E, Cap Andrew P, Dubick Michael A
U.S. Army Institute of Surgical Research, 3698 Chambers Pass, JBSA Fort Sam Houston, San Antonio, TX 78234-6315.
Rice University, 6100 Main Street, Houston, TX 77005.
Mil Med. 2016 May;181(5 Suppl):111-6. doi: 10.7205/MILMED-D-15-00381.
Ibuprofen is commonly used by warfighters in the deployed environment. This study investigated its dose effects on in vitro coagulation in human and pig blood.
Blood samples were collected from 6 normal volunteers and 6 healthy pigs and processed to make platelet-adjusted samples (100 × 10(3)/μL, common transfusion trigger in trauma). Ibuprofen was added to the samples at concentrations of 0 μg/mL (control), the concentration from the highest recommended oral dose (163 μg/mL, 1×), and 2×, 4×, 8×, 10×, 12×, 16×, and 20×. Platelet aggregation by Chrono-Log aggregometer and coagulation by rotational thrombelastogram (Rotem) were assessed at 15 minutes after the addition of ibuprofen.
A robust inhibition of ibuprofen on arachidonic acid-induced platelet aggregation was observed at all doses tested in human or pig blood. Collagen-stimulated platelet aggregation was inhibited starting at 1× in human blood and 4× in pig blood. Rotem measurements were similarly compromised in pig and human blood starting at 16×, except clot formation time was prolonged at 1× in human blood (all p < 0.05).
Ibuprofen inhibited platelet aggregation at recommended doses, and compromised coagulation at higher doses. Human blood was more sensitive to ibuprofen inhibition. Further effort is needed to investigate ibuprofen dose responses on coagulation in vivo.
布洛芬在作战环境中的军人中广泛使用。本研究调查了其对人血和猪血体外凝血的剂量效应。
从6名正常志愿者和6头健康猪采集血样，处理后制成血小板调整样本（100×10³/μL，创伤中常见的输血触发值）。将布洛芬以0μg/mL（对照）、最高推荐口服剂量浓度（163μg/mL，1倍）、2倍、4倍、8倍、10倍、12倍、16倍和20倍的浓度添加到样本中。在添加布洛芬15分钟后，通过Chrono-Log血小板聚集仪评估血小板聚集情况，通过旋转血栓弹力图（Rotem）评估凝血情况。
在人血或猪血中所有测试剂量下均观察到布洛芬对花生四烯酸诱导的血小板聚集有强烈抑制作用。在人血中从1倍剂量开始、在猪血中从4倍剂量开始，胶原刺激的血小板聚集受到抑制。在猪和人血中从16倍剂量开始，Rotem测量结果同样受到影响，不过在人血中1倍剂量时凝血形成时间延长（所有p<0.05）。
布洛芬在推荐剂量下抑制血小板聚集，在高剂量下损害凝血功能。人血对布洛芬抑制作用更敏感。需要进一步研究布洛芬在体内对凝血的剂量反应。
