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Valproic acid modulates platelet and coagulation function ex vivo

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  1. A rare heterozygous variant in FGB (Fibrinogen Merivale) causing hypofibrinogenemia in a Swedish family

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  2. Prediction of bleeding by thromboelastography in ICU patients with haematological malignancy and severe sepsis

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  3. Does whole blood coagulation analysis reflect developmental haemostasis?

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  4. Changes in thrombin generation in children after cardiac surgery and ex-vivo response to blood products and haemostatic agents

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  5. Coagulation competence and fluid recruitment after moderate blood loss in young men

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  1. Developing and validating COVID-19 adverse outcome risk prediction models from a bi-national European cohort of 5594 patients

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  2. Ketamine for rapid sequence intubation in adult trauma patients: A retrospective observational study

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  3. Smoking and risk of surgical bleeding: nationwide analysis of 5,452,411 surgical cases

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  4. Identification of a new genetic variant associated with cholecystitis: a multicenter genome-wide association study

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  5. Red blood cell transfusion in surgery: an observational study of the trends in the USA from 2011 to 2016

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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
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: 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.

Original languageEnglish
JournalBlood coagulation & fibrinolysis : an international journal in haemostasis and thrombosis
Volume28
Issue number6
Pages (from-to)479-484
Number of pages6
ISSN0957-5235
DOIs
Publication statusPublished - Sep 2017

    Research areas

  • Journal Article

ID: 52410970