Platelets play an important role in the activation of coagulation. P2Y12 receptor inhibition may be beneficial in inflammatory states. Prasugrel, a potent irreversible inhibitor of P2Y12 receptor-induced platelet activation may reduce activation of coagulation in a human LPS (lipopolysaccharide) model. A double-blind, randomized, crossover trial with a minimum washout period of 6 weeks was performed. Sixteen subjects were randomly assigned to a treatment group that received prasugrel or placebo 2 h before infusion of a bolus of LPS (2 ng/kg of body weight), whereas four subjects were assigned to a control group receiving prasugrel or placebo without LPS. hcDNA (histone-complexed DNA), coagulation and platelet-specific parameters were measured by enzyme immunoassay. Leucocyte aggregate formation was analysed by flow cytometry, and thromboelastometry was performed. LPS infusion markedly activated coagulation. However, prasugrel did not reduce changes in prothrombin fragments 1 and 2 (F1+2), thrombin–antithrombin complexes, microparticle-associated tissue factor, CD40 ligand, P-selectin, platelet–leucocyte aggregation, hcDNA levels or the coagulation profile measured by thromboelastometry. hcDNA plasma levels increased approximately 6-fold after LPS infusion in both treatment groups, but not in the control groups. Potent irreversible P2Y12 inhibition by prasugrel does not affect LPS-induced coagulation activation. The 6-fold increased hcDNA plasma levels after infusion of LPS indicates the formation of neutrophil extracellular traps during sterile inflammation.
Skip Nav Destination
Article navigation
March 2016
-
Cover Image
Cover Image
Image of immunofluroscence staining of mouse gonads (left – testis and right – ovary) attached to the mesonephros from between embryonic day 12 and 13. Green indicates the sertoli cell protein Anti-Mullerain Hormone (AMH) and red indicates the ovarian protein called Foxl2. Blue indicates DAPI (which stains the nucleus). The antibodies are AMH (MIS) E19 santa Cruz, sc-34833 and Foxl2 Novus NB100-1277. For further details please see pp. 421-432. The image was kindly generated and provided by I. Knarston, K. Ayers and A. Sinclair.
Research Article|
February 04 2016
Potent irreversible P2Y12 inhibition does not reduce LPS-induced coagulation activation in a randomized, double-blind, placebo-controlled trial
Christian Schoergenhofer;
Christian Schoergenhofer
*Department of Clinical Pharmacology, Medical University of Vienna, Währinger Gürtel 18–20, 1090 Vienna, Austria
Search for other works by this author on:
Michael Schwameis;
Michael Schwameis
*Department of Clinical Pharmacology, Medical University of Vienna, Währinger Gürtel 18–20, 1090 Vienna, Austria
Search for other works by this author on:
Eva-Luise Hobl;
Eva-Luise Hobl
*Department of Clinical Pharmacology, Medical University of Vienna, Währinger Gürtel 18–20, 1090 Vienna, Austria
Search for other works by this author on:
Cihan Ay;
Cihan Ay
†Department of Internal Medicine I, Clinical Division of Hematology and Hemostaseology, Medical University of Vienna, Währinger Gürtel 18–20, 1090 Vienna, Austria
Search for other works by this author on:
Nigel S. Key;
Nigel S. Key
‡Hemophilia and Thrombosis Center, Department of Medicine, UNC Chapel Hill, 170 Manning Drive, Chapel Hill, NC 27514, U.S.A.
Search for other works by this author on:
Ulla Derhaschnig;
Ulla Derhaschnig
§Department of Emergency Medicine, Medical University of Vienna, Währinger Gürtel 18–20, 1090 Vienna, Austria
Search for other works by this author on:
Bernd Jilma;
*Department of Clinical Pharmacology, Medical University of Vienna, Währinger Gürtel 18–20, 1090 Vienna, Austria
Correspondence: Professor Dr Bernd Jilma (email Bernd.jilma@meduniwien.ac.at).
Search for other works by this author on:
Alexander O. Spiel
Alexander O. Spiel
§Department of Emergency Medicine, Medical University of Vienna, Währinger Gürtel 18–20, 1090 Vienna, Austria
Search for other works by this author on:
Publisher: Portland Press Ltd
Received:
August 19 2015
Revision Received:
October 21 2015
Accepted:
November 09 2015
Accepted Manuscript online:
November 09 2015
Online ISSN: 1470-8736
Print ISSN: 0143-5221
© 2016 Authors; published by Portland Press Limited
2016
Clin Sci (Lond) (2016) 130 (6): 433–440.
Article history
Received:
August 19 2015
Revision Received:
October 21 2015
Accepted:
November 09 2015
Accepted Manuscript online:
November 09 2015
Connected Content
This is a commentary on:
P2Y12 receptor inhibition and LPS-induced coagulation
Citation
Christian Schoergenhofer, Michael Schwameis, Eva-Luise Hobl, Cihan Ay, Nigel S. Key, Ulla Derhaschnig, Bernd Jilma, Alexander O. Spiel; Potent irreversible P2Y12 inhibition does not reduce LPS-induced coagulation activation in a randomized, double-blind, placebo-controlled trial. Clin Sci (Lond) 1 March 2016; 130 (6): 433–440. doi: https://doi.org/10.1042/CS20150591
Download citation file:
Sign in
Don't already have an account? Register
Sign in to your personal account
You could not be signed in. Please check your email address / username and password and try again.
Captcha Validation Error. Please try again.