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Perfluorocarbons cause thrombocytopenia, changes in RBC morphology and death in a baboon model of systemic inflammation
A perfluorocarbon (PFC) investigated for treatment of traumatic brain injury (TBI) delivers oxygen to support brain function, but causes transient thrombocytopenia. TBI can cause acute inflammation with resulting thrombocytopenia; an interaction between the PFC effects and TBI inflammation might exa...
Autores principales: | , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Public Library of Science
2022
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9803179/ https://www.ncbi.nlm.nih.gov/pubmed/36584001 http://dx.doi.org/10.1371/journal.pone.0279694 |
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author | Pidcoke, Heather F. Delacruz, Wilfred Herzig, Maryanne C. Schaffer, Beverly S. Leazer, Sahar T. Fedyk, Chriselda G. Montogomery, Robbie K. Prat, Nicolas J. Parida, Bijaya K. Aden, James K. Scherer, Michael R. Reddick, Robert L. Shade, Robert E. Cap, Andrew P. |
author_facet | Pidcoke, Heather F. Delacruz, Wilfred Herzig, Maryanne C. Schaffer, Beverly S. Leazer, Sahar T. Fedyk, Chriselda G. Montogomery, Robbie K. Prat, Nicolas J. Parida, Bijaya K. Aden, James K. Scherer, Michael R. Reddick, Robert L. Shade, Robert E. Cap, Andrew P. |
author_sort | Pidcoke, Heather F. |
collection | PubMed |
description | A perfluorocarbon (PFC) investigated for treatment of traumatic brain injury (TBI) delivers oxygen to support brain function, but causes transient thrombocytopenia. TBI can cause acute inflammation with resulting thrombocytopenia; an interaction between the PFC effects and TBI inflammation might exacerbate thrombocytopenia. Therefore, PFC effects on platelet (PLT) function and hemostasis in a lipopolysaccharide (LPS) model of inflammation in the baboon were studied. Animals were randomized to receive saline ±LPS, and ± one of two doses of PFC. PLT count, transmission electron microscopy, and microparticle populations were quantified at baseline (BL) and at 2, 24, 48, 72, and 96 hours; hemostatic parameters for aggregometry and for blood clotting were measured at baseline (BL) and days 3 and 4. Injection of vehicle and LPS caused thrombocytopenia within hours; PFCs caused delayed thrombocytopenia beginning 48 hours post-infusion. LPS+PFC produced a more prolonged PLT decline and decreased clot strength. LPS+PFC increased ADP-stimulated aggregation, but PFC alone did not. Microparticle abundance was greatest in the LPS+PFC groups. LPS+PFC caused diffuse microvascular hemorrhage and death in 2 of 5 baboons in the low dose LPS-PFC group and 2 of 2 in the high dose LPS-PFC group. Necropsy and histology suggested death was caused by shock associated with hemorrhage in multiple organs. Abnormal morphology of platelets and red blood cells were notable for PFC inclusions. In summary, PFC infusion caused clinically significant thrombocytopenia and exacerbated LPS-induced platelet activation. The interaction between these effects resulted in decreased hemostatic capacity, diffuse bleeding, shock and death. |
format | Online Article Text |
id | pubmed-9803179 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | Public Library of Science |
record_format | MEDLINE/PubMed |
spelling | pubmed-98031792022-12-31 Perfluorocarbons cause thrombocytopenia, changes in RBC morphology and death in a baboon model of systemic inflammation Pidcoke, Heather F. Delacruz, Wilfred Herzig, Maryanne C. Schaffer, Beverly S. Leazer, Sahar T. Fedyk, Chriselda G. Montogomery, Robbie K. Prat, Nicolas J. Parida, Bijaya K. Aden, James K. Scherer, Michael R. Reddick, Robert L. Shade, Robert E. Cap, Andrew P. PLoS One Research Article A perfluorocarbon (PFC) investigated for treatment of traumatic brain injury (TBI) delivers oxygen to support brain function, but causes transient thrombocytopenia. TBI can cause acute inflammation with resulting thrombocytopenia; an interaction between the PFC effects and TBI inflammation might exacerbate thrombocytopenia. Therefore, PFC effects on platelet (PLT) function and hemostasis in a lipopolysaccharide (LPS) model of inflammation in the baboon were studied. Animals were randomized to receive saline ±LPS, and ± one of two doses of PFC. PLT count, transmission electron microscopy, and microparticle populations were quantified at baseline (BL) and at 2, 24, 48, 72, and 96 hours; hemostatic parameters for aggregometry and for blood clotting were measured at baseline (BL) and days 3 and 4. Injection of vehicle and LPS caused thrombocytopenia within hours; PFCs caused delayed thrombocytopenia beginning 48 hours post-infusion. LPS+PFC produced a more prolonged PLT decline and decreased clot strength. LPS+PFC increased ADP-stimulated aggregation, but PFC alone did not. Microparticle abundance was greatest in the LPS+PFC groups. LPS+PFC caused diffuse microvascular hemorrhage and death in 2 of 5 baboons in the low dose LPS-PFC group and 2 of 2 in the high dose LPS-PFC group. Necropsy and histology suggested death was caused by shock associated with hemorrhage in multiple organs. Abnormal morphology of platelets and red blood cells were notable for PFC inclusions. In summary, PFC infusion caused clinically significant thrombocytopenia and exacerbated LPS-induced platelet activation. The interaction between these effects resulted in decreased hemostatic capacity, diffuse bleeding, shock and death. Public Library of Science 2022-12-30 /pmc/articles/PMC9803179/ /pubmed/36584001 http://dx.doi.org/10.1371/journal.pone.0279694 Text en https://creativecommons.org/publicdomain/zero/1.0/This is an open access article, free of all copyright, and may be freely reproduced, distributed, transmitted, modified, built upon, or otherwise used by anyone for any lawful purpose. The work is made available under the Creative Commons CC0 (https://creativecommons.org/publicdomain/zero/1.0/) public domain dedication. |
spellingShingle | Research Article Pidcoke, Heather F. Delacruz, Wilfred Herzig, Maryanne C. Schaffer, Beverly S. Leazer, Sahar T. Fedyk, Chriselda G. Montogomery, Robbie K. Prat, Nicolas J. Parida, Bijaya K. Aden, James K. Scherer, Michael R. Reddick, Robert L. Shade, Robert E. Cap, Andrew P. Perfluorocarbons cause thrombocytopenia, changes in RBC morphology and death in a baboon model of systemic inflammation |
title | Perfluorocarbons cause thrombocytopenia, changes in RBC morphology and death in a baboon model of systemic inflammation |
title_full | Perfluorocarbons cause thrombocytopenia, changes in RBC morphology and death in a baboon model of systemic inflammation |
title_fullStr | Perfluorocarbons cause thrombocytopenia, changes in RBC morphology and death in a baboon model of systemic inflammation |
title_full_unstemmed | Perfluorocarbons cause thrombocytopenia, changes in RBC morphology and death in a baboon model of systemic inflammation |
title_short | Perfluorocarbons cause thrombocytopenia, changes in RBC morphology and death in a baboon model of systemic inflammation |
title_sort | perfluorocarbons cause thrombocytopenia, changes in rbc morphology and death in a baboon model of systemic inflammation |
topic | Research Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9803179/ https://www.ncbi.nlm.nih.gov/pubmed/36584001 http://dx.doi.org/10.1371/journal.pone.0279694 |
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