Effect of Ibuprofen dose on platelet aggregation and coagulation in blood samples from pigs.
BACKGROUND
Ibuprofen is commonly used by Soldiers in the deployed environment. This study investigated its dose-effects on in vitro coagulation.


METHODS
Blood samples were collected from 4 normal healthy pigs and were processed to make platelet-adjusted (100×10(3)/μL) blood samples. Ibuprofen was added to the samples at doses of 0 μg/mL (control), recommended oral dose (163 μg/mL, 1×), 2×, 4×, 8×, 10×, 12×, 16×, and 20×. Arachidonic acid or collagen-stimulated platelet aggregation was assessed at 15 minutes after the addition of ibuprofen. Coagulation was assessed with measurements of prothrombin time (PT) and activated partial thromboplastin time (aPTT), and thrombelastography by Rotem.


RESULTS
A robust inhibition of ibuprofen on arachidonic acid-induced platelet aggregation was observed at all doses tested. Collagen-stimulated platelet aggregation was inhibited to 71%±5% and 10%±5% of the control values at ibuprofen doses of 4× and 20×, respectively (both p<0.05). No changes were observed in PT at any dose, but aPTT was prolonged at dose of 16× and 20×. Rotem measurements of coagulation time, clot formation time, maximum clot firmness, and A10 were compromised at dose 16× and 20× (all p<0.05).


CONCLUSIONS
Ibuprofen inhibited platelet aggregation at recommended doses, but did not compromise aPTT or coagulation profile until at 16 times the recommended doses and higher. Further effort is needed to clarify whether there are different dose-responses between human and pig blood samples in trauma situations.
U.S. Army Institute of Surgical Research, Joint Base San Antonio, 3698 Chambers Pass, Fort Sam Houston, TX 78234-6315.
Wenjun Z
WZ
Martini
U.S. Army Institute of Surgical Research, Joint Base San Antonio, 3698 Chambers Pass, Fort Sam Houston, TX 78234-6315.
Rodolfo
R
Deguzman
U.S. Army Institute of Surgical Research, Joint Base San Antonio, 3698 Chambers Pass, Fort Sam Houston, TX 78234-6315.
Cassandra M
CM
Rodriguez
U.S. Army Institute of Surgical Research, Joint Base San Antonio, 3698 Chambers Pass, Fort Sam Houston, TX 78234-6315.
Jessica
J
Guerra
Rice University, 6100 Main Street, Houston, TX 77251.
Angela K
AK
Martini
U.S. Army Medical Research and Materiel Command, 722 Doughten Street/MCMR-RTC, Fort Detrick, MD 21702.
Anthony E
AE
Pusateri
U.S. Army Institute of Surgical Research, Joint Base San Antonio, 3698 Chambers Pass, Fort Sam Houston, TX 78234-6315.
Michael A
MA
Dubick
D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000008:administration & dosage; D001777:Blood Coagulation / Q000187:drug effects*; D001780:Blood Coagulation Tests; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D007052:Ibuprofen / Q000008:administration & dosage*; D010314:Partial Thromboplastin Time; D010974:Platelet Aggregation / Q000187:drug effects*; D011517:Prothrombin Time; D012771:Shock, Hemorrhagic / Q000097:blood / Q000188:drug therapy*; D013552:Swine; D013916:Thrombelastography
D000894:Anti-Inflammatory Agents, Non-Steroidal; D007052:Ibuprofen