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Perfluorocarbons cause thrombocytopenia, changes in RBC morphology and death in a baboon model of systemic inflammation.

Perfluorocarbons cause thrombocytopenia, changes in RBC morphology and death in a baboon model of systemic inflammation.

Authors :
Heather F Pidcoke
Wilfred Delacruz
Maryanne C Herzig
Beverly S Schaffer
Sahar T Leazer
Chriselda G Fedyk
Robbie K Montogomery
Nicolas J Prat
Bijaya K Parida
James K Aden
Michael R Scherer
Robert L Reddick
Robert E Shade
Andrew P Cap
Source :
PLoS ONE, Vol 17, Iss 12, p e0279694 (2022)
Publication Year :
2022
Publisher :
Public Library of Science (PLoS), 2022.

Abstract

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.

Subjects

Subjects :
Medicine
Science

Details

Language :
English
ISSN :
19326203
Volume :
17
Issue :
12
Database :
Directory of Open Access Journals
Journal :
PLoS ONE
Publication Type :
Academic Journal
Accession number :
edsdoj.3faad40b14eefb38de77adbf4c278
Document Type :
article
Full Text :
https://doi.org/10.1371/journal.pone.0279694