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The Effects of Heparins on the Liver: Application of Mechanistic Serum Biomarkers in a Randomized Study in Healthy Volunteers

Heparins have been reported to cause elevations in serum alanine aminotransferase (ALT) and aspartate aminotransferase (AST) but have not been associated with clinically significant liver injury. The mechanisms underlying these benign laboratory abnormalities are unknown. Forty-eight healthy men wer...

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Autores principales: Harrill, A H, Roach, J, Fier, I, Eaddy, J S, Kurtz, C L, Antoine, D J, Spencer, D M, Kishimoto, T K, Pisetsky, D S, Park, B K, Watkins, P B
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BlackWell Publishing Ltd 2012
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4320779/
https://www.ncbi.nlm.nih.gov/pubmed/22739141
http://dx.doi.org/10.1038/clpt.2012.40
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author Harrill, A H
Roach, J
Fier, I
Eaddy, J S
Kurtz, C L
Antoine, D J
Spencer, D M
Kishimoto, T K
Pisetsky, D S
Park, B K
Watkins, P B
author_facet Harrill, A H
Roach, J
Fier, I
Eaddy, J S
Kurtz, C L
Antoine, D J
Spencer, D M
Kishimoto, T K
Pisetsky, D S
Park, B K
Watkins, P B
author_sort Harrill, A H
collection PubMed
description Heparins have been reported to cause elevations in serum alanine aminotransferase (ALT) and aspartate aminotransferase (AST) but have not been associated with clinically significant liver injury. The mechanisms underlying these benign laboratory abnormalities are unknown. Forty-eight healthy men were randomized to receive subcutaneous injections of unfractionated heparin (UFH; 150 U/kg), enoxaparin sodium (1 mg/kg), dalteparin sodium (120 IU/kg), or adomiparin sodium (125 IU/kg; a novel heparin) every 12 h for 4.5 days. Asymptomatic elevations in serum ALT or AST were observed in >90% of the subjects. Elevations were also observed in the levels of serum sorbitol dehydrogenase (SDH), glutamate dehydrogenase (GLDH), miR-122, high-mobility group box-1 protein (including the acetylated form), full-length keratin 18, and DNA. Keratin 18 fragments, which are apoptosis biomarkers, were not detected. Biomarker profiles did not differ significantly across heparin treatments. We conclude that heparins as a class cause self-limited and mild hepatocyte necrosis with secondary activation of an innate immune response.
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spelling pubmed-43207792015-02-13 The Effects of Heparins on the Liver: Application of Mechanistic Serum Biomarkers in a Randomized Study in Healthy Volunteers Harrill, A H Roach, J Fier, I Eaddy, J S Kurtz, C L Antoine, D J Spencer, D M Kishimoto, T K Pisetsky, D S Park, B K Watkins, P B Clin Pharmacol Ther Research Heparins have been reported to cause elevations in serum alanine aminotransferase (ALT) and aspartate aminotransferase (AST) but have not been associated with clinically significant liver injury. The mechanisms underlying these benign laboratory abnormalities are unknown. Forty-eight healthy men were randomized to receive subcutaneous injections of unfractionated heparin (UFH; 150 U/kg), enoxaparin sodium (1 mg/kg), dalteparin sodium (120 IU/kg), or adomiparin sodium (125 IU/kg; a novel heparin) every 12 h for 4.5 days. Asymptomatic elevations in serum ALT or AST were observed in >90% of the subjects. Elevations were also observed in the levels of serum sorbitol dehydrogenase (SDH), glutamate dehydrogenase (GLDH), miR-122, high-mobility group box-1 protein (including the acetylated form), full-length keratin 18, and DNA. Keratin 18 fragments, which are apoptosis biomarkers, were not detected. Biomarker profiles did not differ significantly across heparin treatments. We conclude that heparins as a class cause self-limited and mild hepatocyte necrosis with secondary activation of an innate immune response. BlackWell Publishing Ltd 2012-08 2012-06-27 /pmc/articles/PMC4320779/ /pubmed/22739141 http://dx.doi.org/10.1038/clpt.2012.40 Text en © 2012 American Society for Clinical Pharmacology and Therapeutics http://creativecommons.org/licenses/by-nc-nd/3.0/ This work is licensed under the Creative Commons Attribution-NonCommercial-No Derivative Works 3.0 Unported License. To view a copy of this license, visit http://creativecommons.org/licenses/by-nc-nd/3.0/
spellingShingle Research
Harrill, A H
Roach, J
Fier, I
Eaddy, J S
Kurtz, C L
Antoine, D J
Spencer, D M
Kishimoto, T K
Pisetsky, D S
Park, B K
Watkins, P B
The Effects of Heparins on the Liver: Application of Mechanistic Serum Biomarkers in a Randomized Study in Healthy Volunteers
title The Effects of Heparins on the Liver: Application of Mechanistic Serum Biomarkers in a Randomized Study in Healthy Volunteers
title_full The Effects of Heparins on the Liver: Application of Mechanistic Serum Biomarkers in a Randomized Study in Healthy Volunteers
title_fullStr The Effects of Heparins on the Liver: Application of Mechanistic Serum Biomarkers in a Randomized Study in Healthy Volunteers
title_full_unstemmed The Effects of Heparins on the Liver: Application of Mechanistic Serum Biomarkers in a Randomized Study in Healthy Volunteers
title_short The Effects of Heparins on the Liver: Application of Mechanistic Serum Biomarkers in a Randomized Study in Healthy Volunteers
title_sort effects of heparins on the liver: application of mechanistic serum biomarkers in a randomized study in healthy volunteers
topic Research
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4320779/
https://www.ncbi.nlm.nih.gov/pubmed/22739141
http://dx.doi.org/10.1038/clpt.2012.40
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