Intravenous Hemostatic Nanoparticles Increase Survival Following Blunt Trauma Injury

Trauma is the leading cause of death for people ages 1–44, with blood loss comprising 60–70% of mortality in the absence of lethal CNS or cardiac injury. Immediate intervention is critical to improving chances of survival. While there are several products to control bleeding for external and compres...

Ausführliche Beschreibung

Gespeichert in:
Bibliographische Detailangaben
Veröffentlicht in:Biomacromolecules 2012-11, Vol.13 (11), p.3850-3857
Hauptverfasser: Shoffstall, Andrew J, Atkins, Kristyn T, Groynom, Rebecca E, Varley, Matthew E, Everhart, Lydia M, Lashof-Sullivan, Margaret M, Martyn-Dow, Blaine, Butler, Robert S, Ustin, Jeffrey S, Lavik, Erin B
Format: Artikel
Sprache:eng
Schlagworte:
Online-Zugang:Volltext
Tags: Tag hinzufügen
Keine Tags, Fügen Sie den ersten Tag hinzu!
container_end_page 3857
container_issue 11
container_start_page 3850
container_title Biomacromolecules
container_volume 13
creator Shoffstall, Andrew J
Atkins, Kristyn T
Groynom, Rebecca E
Varley, Matthew E
Everhart, Lydia M
Lashof-Sullivan, Margaret M
Martyn-Dow, Blaine
Butler, Robert S
Ustin, Jeffrey S
Lavik, Erin B
description Trauma is the leading cause of death for people ages 1–44, with blood loss comprising 60–70% of mortality in the absence of lethal CNS or cardiac injury. Immediate intervention is critical to improving chances of survival. While there are several products to control bleeding for external and compressible wounds, including pressure dressings, tourniquets, or topical materials (e.g., QuikClot, HemCon), there are no products that can be administered in the field for internal bleeding. There is a tremendous unmet need for a hemostatic agent to address internal bleeding in the field. We have developed hemostatic nanoparticles (GRGDS-NPs) that reduce bleeding times by ∼50% in a rat femoral artery injury model. Here, we investigated their impact on survival following administration in a lethal liver resection injury in rats. Administration of these hemostatic nanoparticles reduced blood loss following the liver injury and dramatically and significantly increased 1 h survival from 40 and 47% in controls (inactive nanoparticles and saline, respectively) to 80%. Furthermore, we saw no complications following administration of these nanoparticles. We further characterized the nanoparticles’ effect on clotting time (CT) and maximum clot firmness (MCF) using rotational thromboelastometry (ROTEM), a clinical measurement of whole-blood coagulation. Clotting time is significantly reduced, with no change in MCF. Administration of these hemostatic nanoparticles after massive trauma may help staunch bleeding and improve survival in the critical window following injury, and this could fundamentally change trauma care.
doi_str_mv 10.1021/bm3013023
format Article
fullrecord <record><control><sourceid>proquest_pubme</sourceid><recordid>TN_cdi_pubmedcentral_primary_oai_pubmedcentral_nih_gov_3496064</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><sourcerecordid>1524409384</sourcerecordid><originalsourceid>FETCH-LOGICAL-a468t-9b17a7f51428bbdd969fa64493d4a218f2e20710631d7704a0f8ab2cea735d6d3</originalsourceid><addsrcrecordid>eNptkU1P3DAQhq0KVCjtoX-gygWJHkL9FTu-IMGqwEqIHro9WxPHoVk59tZOFvHv64VlAYnTjDSP3rGfQegrwacEU_KjGRgmDFP2AR2SioqSC0z3HvuqlFLJA_QppSXGWDFefUQHlCpVS0kP0WLuxwhr68OUims7hDTC2JviFnxYQcyts6mYexMtJFv8nuK6X4MrLoNz4b73d8WFm_xYLCJMA2RwOcWHz2i_A5fsl209Qn8ufy5m1-XNr6v57PymBC7qsVQNkSC7inBaN03bKqE6EJwr1nKgpO6opVgSLBhppcQccFdDQ40FyapWtOwInT3lrqZmsK2xm784vYr9APFBB-j124nv_-q7sNaMK4EFzwEn24AY_k02jXrok7HOgbdZiM4COc_S6g36_Qk1MaQUbbdbQ7DeXEHvrpDZb6_ftSOftWfgeAtAMuC6CN706YUTAjOG5QsHJullmKLPOt9Z-B_Mopw6</addsrcrecordid><sourcetype>Open Access Repository</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype><pqid>1524409384</pqid></control><display><type>article</type><title>Intravenous Hemostatic Nanoparticles Increase Survival Following Blunt Trauma Injury</title><source>MEDLINE</source><source>American Chemical Society Journals</source><creator>Shoffstall, Andrew J ; Atkins, Kristyn T ; Groynom, Rebecca E ; Varley, Matthew E ; Everhart, Lydia M ; Lashof-Sullivan, Margaret M ; Martyn-Dow, Blaine ; Butler, Robert S ; Ustin, Jeffrey S ; Lavik, Erin B</creator><creatorcontrib>Shoffstall, Andrew J ; Atkins, Kristyn T ; Groynom, Rebecca E ; Varley, Matthew E ; Everhart, Lydia M ; Lashof-Sullivan, Margaret M ; Martyn-Dow, Blaine ; Butler, Robert S ; Ustin, Jeffrey S ; Lavik, Erin B</creatorcontrib><description>Trauma is the leading cause of death for people ages 1–44, with blood loss comprising 60–70% of mortality in the absence of lethal CNS or cardiac injury. Immediate intervention is critical to improving chances of survival. While there are several products to control bleeding for external and compressible wounds, including pressure dressings, tourniquets, or topical materials (e.g., QuikClot, HemCon), there are no products that can be administered in the field for internal bleeding. There is a tremendous unmet need for a hemostatic agent to address internal bleeding in the field. We have developed hemostatic nanoparticles (GRGDS-NPs) that reduce bleeding times by ∼50% in a rat femoral artery injury model. Here, we investigated their impact on survival following administration in a lethal liver resection injury in rats. Administration of these hemostatic nanoparticles reduced blood loss following the liver injury and dramatically and significantly increased 1 h survival from 40 and 47% in controls (inactive nanoparticles and saline, respectively) to 80%. Furthermore, we saw no complications following administration of these nanoparticles. We further characterized the nanoparticles’ effect on clotting time (CT) and maximum clot firmness (MCF) using rotational thromboelastometry (ROTEM), a clinical measurement of whole-blood coagulation. Clotting time is significantly reduced, with no change in MCF. Administration of these hemostatic nanoparticles after massive trauma may help staunch bleeding and improve survival in the critical window following injury, and this could fundamentally change trauma care.</description><identifier>ISSN: 1525-7797</identifier><identifier>EISSN: 1526-4602</identifier><identifier>DOI: 10.1021/bm3013023</identifier><identifier>PMID: 22998772</identifier><language>eng</language><publisher>Washington, DC: American Chemical Society</publisher><subject>Animals ; Applied sciences ; Biological and medical sciences ; Blood Coagulation - drug effects ; Blood. Blood coagulation. Reticuloendothelial system ; Disease Models, Animal ; Exact sciences and technology ; Femoral Artery - injuries ; Forms of application and semi-finished materials ; Hemorrhage - therapy ; Hemostatic Techniques ; Hemostatics - administration &amp; dosage ; Hemostatics - therapeutic use ; Liver - injuries ; Medical sciences ; Miscellaneous ; Nanoparticles - administration &amp; dosage ; Nanoparticles - therapeutic use ; Pharmacology. Drug treatments ; Polyethylene Glycols - therapeutic use ; Polyglactin 910 - therapeutic use ; Polymer industry, paints, wood ; Rats ; Rats, Sprague-Dawley ; Survival ; Technology of polymers ; Wounds, Nonpenetrating - mortality ; Wounds, Nonpenetrating - therapy</subject><ispartof>Biomacromolecules, 2012-11, Vol.13 (11), p.3850-3857</ispartof><rights>Copyright © 2012 American Chemical Society</rights><rights>2014 INIST-CNRS</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-a468t-9b17a7f51428bbdd969fa64493d4a218f2e20710631d7704a0f8ab2cea735d6d3</citedby><cites>FETCH-LOGICAL-a468t-9b17a7f51428bbdd969fa64493d4a218f2e20710631d7704a0f8ab2cea735d6d3</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://pubs.acs.org/doi/pdf/10.1021/bm3013023$$EPDF$$P50$$Gacs$$H</linktopdf><linktohtml>$$Uhttps://pubs.acs.org/doi/10.1021/bm3013023$$EHTML$$P50$$Gacs$$H</linktohtml><link.rule.ids>230,314,780,784,885,2765,27076,27924,27925,56738,56788</link.rule.ids><backlink>$$Uhttp://pascal-francis.inist.fr/vibad/index.php?action=getRecordDetail&amp;idt=26603307$$DView record in Pascal Francis$$Hfree_for_read</backlink><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/22998772$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Shoffstall, Andrew J</creatorcontrib><creatorcontrib>Atkins, Kristyn T</creatorcontrib><creatorcontrib>Groynom, Rebecca E</creatorcontrib><creatorcontrib>Varley, Matthew E</creatorcontrib><creatorcontrib>Everhart, Lydia M</creatorcontrib><creatorcontrib>Lashof-Sullivan, Margaret M</creatorcontrib><creatorcontrib>Martyn-Dow, Blaine</creatorcontrib><creatorcontrib>Butler, Robert S</creatorcontrib><creatorcontrib>Ustin, Jeffrey S</creatorcontrib><creatorcontrib>Lavik, Erin B</creatorcontrib><title>Intravenous Hemostatic Nanoparticles Increase Survival Following Blunt Trauma Injury</title><title>Biomacromolecules</title><addtitle>Biomacromolecules</addtitle><description>Trauma is the leading cause of death for people ages 1–44, with blood loss comprising 60–70% of mortality in the absence of lethal CNS or cardiac injury. Immediate intervention is critical to improving chances of survival. While there are several products to control bleeding for external and compressible wounds, including pressure dressings, tourniquets, or topical materials (e.g., QuikClot, HemCon), there are no products that can be administered in the field for internal bleeding. There is a tremendous unmet need for a hemostatic agent to address internal bleeding in the field. We have developed hemostatic nanoparticles (GRGDS-NPs) that reduce bleeding times by ∼50% in a rat femoral artery injury model. Here, we investigated their impact on survival following administration in a lethal liver resection injury in rats. Administration of these hemostatic nanoparticles reduced blood loss following the liver injury and dramatically and significantly increased 1 h survival from 40 and 47% in controls (inactive nanoparticles and saline, respectively) to 80%. Furthermore, we saw no complications following administration of these nanoparticles. We further characterized the nanoparticles’ effect on clotting time (CT) and maximum clot firmness (MCF) using rotational thromboelastometry (ROTEM), a clinical measurement of whole-blood coagulation. Clotting time is significantly reduced, with no change in MCF. Administration of these hemostatic nanoparticles after massive trauma may help staunch bleeding and improve survival in the critical window following injury, and this could fundamentally change trauma care.</description><subject>Animals</subject><subject>Applied sciences</subject><subject>Biological and medical sciences</subject><subject>Blood Coagulation - drug effects</subject><subject>Blood. Blood coagulation. Reticuloendothelial system</subject><subject>Disease Models, Animal</subject><subject>Exact sciences and technology</subject><subject>Femoral Artery - injuries</subject><subject>Forms of application and semi-finished materials</subject><subject>Hemorrhage - therapy</subject><subject>Hemostatic Techniques</subject><subject>Hemostatics - administration &amp; dosage</subject><subject>Hemostatics - therapeutic use</subject><subject>Liver - injuries</subject><subject>Medical sciences</subject><subject>Miscellaneous</subject><subject>Nanoparticles - administration &amp; dosage</subject><subject>Nanoparticles - therapeutic use</subject><subject>Pharmacology. Drug treatments</subject><subject>Polyethylene Glycols - therapeutic use</subject><subject>Polyglactin 910 - therapeutic use</subject><subject>Polymer industry, paints, wood</subject><subject>Rats</subject><subject>Rats, Sprague-Dawley</subject><subject>Survival</subject><subject>Technology of polymers</subject><subject>Wounds, Nonpenetrating - mortality</subject><subject>Wounds, Nonpenetrating - therapy</subject><issn>1525-7797</issn><issn>1526-4602</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2012</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNptkU1P3DAQhq0KVCjtoX-gygWJHkL9FTu-IMGqwEqIHro9WxPHoVk59tZOFvHv64VlAYnTjDSP3rGfQegrwacEU_KjGRgmDFP2AR2SioqSC0z3HvuqlFLJA_QppSXGWDFefUQHlCpVS0kP0WLuxwhr68OUims7hDTC2JviFnxYQcyts6mYexMtJFv8nuK6X4MrLoNz4b73d8WFm_xYLCJMA2RwOcWHz2i_A5fsl209Qn8ufy5m1-XNr6v57PymBC7qsVQNkSC7inBaN03bKqE6EJwr1nKgpO6opVgSLBhppcQccFdDQ40FyapWtOwInT3lrqZmsK2xm784vYr9APFBB-j124nv_-q7sNaMK4EFzwEn24AY_k02jXrok7HOgbdZiM4COc_S6g36_Qk1MaQUbbdbQ7DeXEHvrpDZb6_ftSOftWfgeAtAMuC6CN706YUTAjOG5QsHJullmKLPOt9Z-B_Mopw6</recordid><startdate>20121112</startdate><enddate>20121112</enddate><creator>Shoffstall, Andrew J</creator><creator>Atkins, Kristyn T</creator><creator>Groynom, Rebecca E</creator><creator>Varley, Matthew E</creator><creator>Everhart, Lydia M</creator><creator>Lashof-Sullivan, Margaret M</creator><creator>Martyn-Dow, Blaine</creator><creator>Butler, Robert S</creator><creator>Ustin, Jeffrey S</creator><creator>Lavik, Erin B</creator><general>American Chemical Society</general><scope>IQODW</scope><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>7QO</scope><scope>8FD</scope><scope>FR3</scope><scope>P64</scope><scope>5PM</scope></search><sort><creationdate>20121112</creationdate><title>Intravenous Hemostatic Nanoparticles Increase Survival Following Blunt Trauma Injury</title><author>Shoffstall, Andrew J ; Atkins, Kristyn T ; Groynom, Rebecca E ; Varley, Matthew E ; Everhart, Lydia M ; Lashof-Sullivan, Margaret M ; Martyn-Dow, Blaine ; Butler, Robert S ; Ustin, Jeffrey S ; Lavik, Erin B</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-a468t-9b17a7f51428bbdd969fa64493d4a218f2e20710631d7704a0f8ab2cea735d6d3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2012</creationdate><topic>Animals</topic><topic>Applied sciences</topic><topic>Biological and medical sciences</topic><topic>Blood Coagulation - drug effects</topic><topic>Blood. Blood coagulation. Reticuloendothelial system</topic><topic>Disease Models, Animal</topic><topic>Exact sciences and technology</topic><topic>Femoral Artery - injuries</topic><topic>Forms of application and semi-finished materials</topic><topic>Hemorrhage - therapy</topic><topic>Hemostatic Techniques</topic><topic>Hemostatics - administration &amp; dosage</topic><topic>Hemostatics - therapeutic use</topic><topic>Liver - injuries</topic><topic>Medical sciences</topic><topic>Miscellaneous</topic><topic>Nanoparticles - administration &amp; dosage</topic><topic>Nanoparticles - therapeutic use</topic><topic>Pharmacology. Drug treatments</topic><topic>Polyethylene Glycols - therapeutic use</topic><topic>Polyglactin 910 - therapeutic use</topic><topic>Polymer industry, paints, wood</topic><topic>Rats</topic><topic>Rats, Sprague-Dawley</topic><topic>Survival</topic><topic>Technology of polymers</topic><topic>Wounds, Nonpenetrating - mortality</topic><topic>Wounds, Nonpenetrating - therapy</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Shoffstall, Andrew J</creatorcontrib><creatorcontrib>Atkins, Kristyn T</creatorcontrib><creatorcontrib>Groynom, Rebecca E</creatorcontrib><creatorcontrib>Varley, Matthew E</creatorcontrib><creatorcontrib>Everhart, Lydia M</creatorcontrib><creatorcontrib>Lashof-Sullivan, Margaret M</creatorcontrib><creatorcontrib>Martyn-Dow, Blaine</creatorcontrib><creatorcontrib>Butler, Robert S</creatorcontrib><creatorcontrib>Ustin, Jeffrey S</creatorcontrib><creatorcontrib>Lavik, Erin B</creatorcontrib><collection>Pascal-Francis</collection><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>Biotechnology Research Abstracts</collection><collection>Technology Research Database</collection><collection>Engineering Research Database</collection><collection>Biotechnology and BioEngineering Abstracts</collection><collection>PubMed Central (Full Participant titles)</collection><jtitle>Biomacromolecules</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Shoffstall, Andrew J</au><au>Atkins, Kristyn T</au><au>Groynom, Rebecca E</au><au>Varley, Matthew E</au><au>Everhart, Lydia M</au><au>Lashof-Sullivan, Margaret M</au><au>Martyn-Dow, Blaine</au><au>Butler, Robert S</au><au>Ustin, Jeffrey S</au><au>Lavik, Erin B</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Intravenous Hemostatic Nanoparticles Increase Survival Following Blunt Trauma Injury</atitle><jtitle>Biomacromolecules</jtitle><addtitle>Biomacromolecules</addtitle><date>2012-11-12</date><risdate>2012</risdate><volume>13</volume><issue>11</issue><spage>3850</spage><epage>3857</epage><pages>3850-3857</pages><issn>1525-7797</issn><eissn>1526-4602</eissn><abstract>Trauma is the leading cause of death for people ages 1–44, with blood loss comprising 60–70% of mortality in the absence of lethal CNS or cardiac injury. Immediate intervention is critical to improving chances of survival. While there are several products to control bleeding for external and compressible wounds, including pressure dressings, tourniquets, or topical materials (e.g., QuikClot, HemCon), there are no products that can be administered in the field for internal bleeding. There is a tremendous unmet need for a hemostatic agent to address internal bleeding in the field. We have developed hemostatic nanoparticles (GRGDS-NPs) that reduce bleeding times by ∼50% in a rat femoral artery injury model. Here, we investigated their impact on survival following administration in a lethal liver resection injury in rats. Administration of these hemostatic nanoparticles reduced blood loss following the liver injury and dramatically and significantly increased 1 h survival from 40 and 47% in controls (inactive nanoparticles and saline, respectively) to 80%. Furthermore, we saw no complications following administration of these nanoparticles. We further characterized the nanoparticles’ effect on clotting time (CT) and maximum clot firmness (MCF) using rotational thromboelastometry (ROTEM), a clinical measurement of whole-blood coagulation. Clotting time is significantly reduced, with no change in MCF. Administration of these hemostatic nanoparticles after massive trauma may help staunch bleeding and improve survival in the critical window following injury, and this could fundamentally change trauma care.</abstract><cop>Washington, DC</cop><pub>American Chemical Society</pub><pmid>22998772</pmid><doi>10.1021/bm3013023</doi><tpages>8</tpages><oa>free_for_read</oa></addata></record>
fulltext fulltext
identifier ISSN: 1525-7797
ispartof Biomacromolecules, 2012-11, Vol.13 (11), p.3850-3857
issn 1525-7797
1526-4602
language eng
recordid cdi_pubmedcentral_primary_oai_pubmedcentral_nih_gov_3496064
source MEDLINE; American Chemical Society Journals
subjects Animals
Applied sciences
Biological and medical sciences
Blood Coagulation - drug effects
Blood. Blood coagulation. Reticuloendothelial system
Disease Models, Animal
Exact sciences and technology
Femoral Artery - injuries
Forms of application and semi-finished materials
Hemorrhage - therapy
Hemostatic Techniques
Hemostatics - administration & dosage
Hemostatics - therapeutic use
Liver - injuries
Medical sciences
Miscellaneous
Nanoparticles - administration & dosage
Nanoparticles - therapeutic use
Pharmacology. Drug treatments
Polyethylene Glycols - therapeutic use
Polyglactin 910 - therapeutic use
Polymer industry, paints, wood
Rats
Rats, Sprague-Dawley
Survival
Technology of polymers
Wounds, Nonpenetrating - mortality
Wounds, Nonpenetrating - therapy
title Intravenous Hemostatic Nanoparticles Increase Survival Following Blunt Trauma Injury
url https://sfx.bib-bvb.de/sfx_tum?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&ctx_tim=2025-01-01T23%3A15%3A41IST&url_ver=Z39.88-2004&url_ctx_fmt=infofi/fmt:kev:mtx:ctx&rfr_id=info:sid/primo.exlibrisgroup.com:primo3-Article-proquest_pubme&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.atitle=Intravenous%20Hemostatic%20Nanoparticles%20Increase%20Survival%20Following%20Blunt%20Trauma%20Injury&rft.jtitle=Biomacromolecules&rft.au=Shoffstall,%20Andrew%20J&rft.date=2012-11-12&rft.volume=13&rft.issue=11&rft.spage=3850&rft.epage=3857&rft.pages=3850-3857&rft.issn=1525-7797&rft.eissn=1526-4602&rft_id=info:doi/10.1021/bm3013023&rft_dat=%3Cproquest_pubme%3E1524409384%3C/proquest_pubme%3E%3Curl%3E%3C/url%3E&disable_directlink=true&sfx.directlink=off&sfx.report_link=0&rft_id=info:oai/&rft_pqid=1524409384&rft_id=info:pmid/22998772&rfr_iscdi=true