TY  - JOUR
A1  - Morris, Mackenzie C.
A1  - Kassam, Farzaan
A1  - Bercz, Aron
A1  - Beckmann, Nadine
A1  - Schumacher, Fabian
A1  - Gulbins, Erich
A1  - Makley, Amy T.
A1  - Goodman, Michael D.
T1  - The Role of Chemoprophylactic Agents in Modulating Platelet Aggregability After Traumatic Brain Injury
JF  - Journal of surgical research
N2  - Background: The pathophysiology behind the subacute but persistent hypercoagulable state after traumatic brain injury (TBI) is poorly understood but contributes to morbidity induced by venous thromboembolism. Because platelets and their microvesicles have been hypothesized to play a role in post-traumatic hypercoagulability, administration of commonly used agents may ameliorate this coagulability. We hypothesized that utilization of aspirin, ketorolac, amitriptyline, unfractionated heparin, or enoxaparin would modulate the platelet aggregation response after TBI. Methods: Concussive TBI was induced by weight drop. Mice were then randomized to receive aspirin, ketorolac, amitriptyline, heparin, enoxaparin, or saline control at 2 and 8 h after TBI. Mice were sacrificed at 6 or 24 h after injury to determine coagulability by rotational thromboelastometry (ROTEM), platelet function testing with impedance aggregometry, and microvesicle enumeration. Platelet sphingolipid metabolites were analyzed by mass spectrometry. Results: ROTEM demonstrated increased platelet contribution to maximum clot firmness at 6 h after TBI in mice that received aspirin or amitriptyline, but this did not persist at 24 h. By contrast, adenosine diphosphate- and arachidonic acid-induced platelet aggregation at 6 h was significantly lower in mice receiving ketorolac, aspirin, and amitriptyline compared with mice receiving saline at 6 h after injury and only arachidonic acid-initiated platelet aggregation was decreased by aspirin at 24 h. There were no differences in microvesicle production at either time point. Platelet sphingosine-1-phosphate levels were decreased at 6 h in the group receiving amitriptyline and increased at 24 h along with platelet ceramide levels at 24 h in the amitriptyline group. Conclusion: After TBI, amitriptyline decreased platelet aggregability and increased contribution to clot in a manner similar to aspirin. The amitriptyline effects on platelet function and sphingolipid metabolites may represent a possible role of the acid sphingomyelinase in the hypercoagulability observed after injury. In addition, inhibition of platelet reactivity may be an underappreciated benefit of low molecular weight heparins, such as enoxaparin. (C) 2019 Elsevier Inc. All rights reserved.
KW  - Trauma
KW  - Traumatic brain injury
KW  - Venous thromboembolism
KW  - Chemoprophylaxis
KW  - Sphingolipids
Y1  - 2019
U6  - https://doi.org/10.1016/j.jss.2019.06.022
SN  - 0022-4804
SN  - 1095-8673
VL  - 244
SP  - 1
EP  - 8
PB  - Elsevier
CY  - San Diego
ER  -