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Valproic acid modulates platelet and coagulation function ex vivo

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  • Ted Bambakidis
  • Simone E Dekker
  • Ihab Halaweish
  • Baoling Liu
  • Vahagn C Nikolian
  • Patrick E Georgoff
  • Patryk Piascik
  • Yongqing Li
  • Martin Sillesen
  • Hasan B Alam
Vis graf over relationer

: Trauma-induced coagulopathy is associated with adverse patient outcome. Animal models demonstrate that histone deacetylase inhibitors, such as valproic acid (VPA), improve survival following injury. While in-vivo data suggest that improved survival may in part be because of an attenuation of coagulopathy, it remains unknown whether this is a direct effect of the drug, or the establishment of an overall prosurvival phenotype. We thus conducted an ex-vivo experiment to determine if VPA has an effect on coagulation and platelet function. Ten swine were subjected to traumatic brain injury (TBI) and hemorrhagic shock (HS). Blood samples were drawn prior to TBI+HS insult (Healthy group) and 2 h following TBI+HS (Shock group). Samples were incubated with VPA or vehicle controls for 1 h. Platelet aggregation was analyzed via impedance aggregometry and coagulation was measured using thromboelastography. Addition of VPA to the healthy blood did not affect platelet aggregation or coagulation parameters. In shock blood, incubation with VPA significantly reduced collagen-(P = 0.050), arachidonic acid-(P = 0.005), and adenosine diphosphate-(P = 0.023) induced platelet aggregation. VPA also significantly increased the clot strength (P = 0.002) and clot formation rate (P = 0.011). This is the first study to investigate the effect of VPA on platelet function ex vivo. Our results suggest that VPA has no effect on normal blood, but it decreases platelet activation and improves clot dynamics (strength and rate of formation) in blood from shocked animals. This suggests that VPA is capable of exerting a selective platelet sparing effect while enhancing the clot integrity.

OriginalsprogEngelsk
TidsskriftBlood coagulation & fibrinolysis : an international journal in haemostasis and thrombosis
Vol/bind28
Udgave nummer6
Sider (fra-til)479-484
Antal sider6
ISSN0957-5235
DOI
StatusUdgivet - sep. 2017

ID: 52410970