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...
Gespeichert in:
Veröffentlicht in: | Biomacromolecules 2012-11, Vol.13 (11), p.3850-3857 |
---|---|
Hauptverfasser: | , , , , , , , , , |
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 & 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</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&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 & dosage</subject><subject>Hemostatics - therapeutic use</subject><subject>Liver - injuries</subject><subject>Medical sciences</subject><subject>Miscellaneous</subject><subject>Nanoparticles - administration & 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 & dosage</topic><topic>Hemostatics - therapeutic use</topic><topic>Liver - injuries</topic><topic>Medical sciences</topic><topic>Miscellaneous</topic><topic>Nanoparticles - administration & 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 |