Differential Contributions of Intrinsic and Extrinsic Pathways to Thrombin Generation in Adult, Maternal and Cord Plasma Samples
Thrombin generation (TG) is a pivotal process in achieving hemostasis. Coagulation profiles during pregnancy and early neonatal period are different from that of normal (non-pregnant) adults. In this ex vivo study, the differences in TG in maternal and cord plasma relative to normal adult plasma wer...
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| description | Thrombin generation (TG) is a pivotal process in achieving hemostasis. Coagulation profiles during pregnancy and early neonatal period are different from that of normal (non-pregnant) adults. In this ex vivo study, the differences in TG in maternal and cord plasma relative to normal adult plasma were studied.
Twenty consented pregnant women and ten consented healthy adults were included in the study. Maternal and cord blood samples were collected at the time of delivery. Platelet-poor plasma was isolated for the measurement of TG. In some samples, anti-FIXa aptamer, RB006, or a TFPI inhibitor, BAX499 were added to elucidate the contribution of intrinsic and extrinsic pathway to TG. Additionally, procoagulant and inhibitor levels were measured in maternal and cord plasma, and these values were used to mathematically simulate TG.
Peak TG was increased in maternal plasma (393.6±57.9 nM) compared to adult and cord samples (323.2±38.9 nM and 209.9±29.5 nM, respectively). Inhibitory effects of RB006 on TG were less robust in maternal or cord plasma (52% vs. 12% respectively) than in adult plasma (81%). Likewise the effectiveness of BAX499 as represented by the increase in peak TG was much greater in adult (21%) than in maternal (10%) or cord plasma (12%). Further, BAX499 was more effective in reversing RB006 in adult plasma than in maternal or cord plasma. Ex vivo data were reproducible with the results of the mathematical simulation of TG.
Normal parturient plasma shows a large intrinsic pathway reserve for TG compared to adult and cord plasma, while TG in cord plasma is sustained by extrinsic pathway, and low levels of TFPI and AT. |
| doi_str_mv | 10.1371/journal.pone.0154127 |
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Twenty consented pregnant women and ten consented healthy adults were included in the study. Maternal and cord blood samples were collected at the time of delivery. Platelet-poor plasma was isolated for the measurement of TG. In some samples, anti-FIXa aptamer, RB006, or a TFPI inhibitor, BAX499 were added to elucidate the contribution of intrinsic and extrinsic pathway to TG. Additionally, procoagulant and inhibitor levels were measured in maternal and cord plasma, and these values were used to mathematically simulate TG.
Peak TG was increased in maternal plasma (393.6±57.9 nM) compared to adult and cord samples (323.2±38.9 nM and 209.9±29.5 nM, respectively). Inhibitory effects of RB006 on TG were less robust in maternal or cord plasma (52% vs. 12% respectively) than in adult plasma (81%). Likewise the effectiveness of BAX499 as represented by the increase in peak TG was much greater in adult (21%) than in maternal (10%) or cord plasma (12%). Further, BAX499 was more effective in reversing RB006 in adult plasma than in maternal or cord plasma. Ex vivo data were reproducible with the results of the mathematical simulation of TG.
Normal parturient plasma shows a large intrinsic pathway reserve for TG compared to adult and cord plasma, while TG in cord plasma is sustained by extrinsic pathway, and low levels of TFPI and AT.</description><identifier>ISSN: 1932-6203</identifier><identifier>EISSN: 1932-6203</identifier><identifier>DOI: 10.1371/journal.pone.0154127</identifier><identifier>PMID: 27196067</identifier><language>eng</language><publisher>United States: Public Library of Science</publisher><subject>Adult ; Adults ; Anesthesiology ; Anticoagulants ; Aptamers ; Aptamers, Nucleotide - chemistry ; Biology and Life Sciences ; Blood Coagulation ; Blood Coagulation Tests ; Calibration ; Case-Control Studies ; Coagulants - chemistry ; Coagulation ; Computer Simulation ; Cord blood ; Factor IXa - antagonists & inhibitors ; Female ; Fetal Blood - metabolism ; Genetic aspects ; Gynecology ; Hemostasis ; Hemostatics ; Humans ; Inhibitors ; Mathematical models ; Medicine and Health Sciences ; Models, Statistical ; Models, Theoretical ; Neonates ; Newborn babies ; Obstetrics ; People and Places ; Physiological aspects ; Plasma - metabolism ; Pregnancy ; Research and Analysis Methods ; Reversing ; Review boards ; Robustness (mathematics) ; Thrombin ; Thrombin - biosynthesis ; Thrombosis ; Young Adult</subject><ispartof>PloS one, 2016-05, Vol.11 (5), p.e0154127-e0154127</ispartof><rights>COPYRIGHT 2016 Public Library of Science</rights><rights>2016 Rice et al. This is an open access article distributed under the terms of the Creative Commons Attribution License: http://creativecommons.org/licenses/by/4.0/ (the “License”), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.</rights><rights>2016 Rice et al 2016 Rice et al</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c692t-23008955c7560d38c423aa79c046af3aaf21057a7f38e2321d047b93ec52ea133</citedby><cites>FETCH-LOGICAL-c692t-23008955c7560d38c423aa79c046af3aaf21057a7f38e2321d047b93ec52ea133</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC4873248/pdf/$$EPDF$$P50$$Gpubmedcentral$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC4873248/$$EHTML$$P50$$Gpubmedcentral$$Hfree_for_read</linktohtml><link.rule.ids>230,314,723,776,780,860,881,2095,2914,23846,27903,27904,53769,53771,79346,79347</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/27196067$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><contributor>Kanellopoulos-Langevin, Colette</contributor><creatorcontrib>Rice, Nicklaus T</creatorcontrib><creatorcontrib>Szlam, Fania</creatorcontrib><creatorcontrib>Varner, Jeffrey D</creatorcontrib><creatorcontrib>Bernstein, Peter S</creatorcontrib><creatorcontrib>Szlam, Arthur D</creatorcontrib><creatorcontrib>Tanaka, Kenichi A</creatorcontrib><title>Differential Contributions of Intrinsic and Extrinsic Pathways to Thrombin Generation in Adult, Maternal and Cord Plasma Samples</title><title>PloS one</title><addtitle>PLoS One</addtitle><description>Thrombin generation (TG) is a pivotal process in achieving hemostasis. Coagulation profiles during pregnancy and early neonatal period are different from that of normal (non-pregnant) adults. In this ex vivo study, the differences in TG in maternal and cord plasma relative to normal adult plasma were studied.
Twenty consented pregnant women and ten consented healthy adults were included in the study. Maternal and cord blood samples were collected at the time of delivery. Platelet-poor plasma was isolated for the measurement of TG. In some samples, anti-FIXa aptamer, RB006, or a TFPI inhibitor, BAX499 were added to elucidate the contribution of intrinsic and extrinsic pathway to TG. Additionally, procoagulant and inhibitor levels were measured in maternal and cord plasma, and these values were used to mathematically simulate TG.
Peak TG was increased in maternal plasma (393.6±57.9 nM) compared to adult and cord samples (323.2±38.9 nM and 209.9±29.5 nM, respectively). Inhibitory effects of RB006 on TG were less robust in maternal or cord plasma (52% vs. 12% respectively) than in adult plasma (81%). Likewise the effectiveness of BAX499 as represented by the increase in peak TG was much greater in adult (21%) than in maternal (10%) or cord plasma (12%). Further, BAX499 was more effective in reversing RB006 in adult plasma than in maternal or cord plasma. Ex vivo data were reproducible with the results of the mathematical simulation of TG.
Normal parturient plasma shows a large intrinsic pathway reserve for TG compared to adult and cord plasma, while TG in cord plasma is sustained by extrinsic pathway, and low levels of TFPI and AT.</description><subject>Adult</subject><subject>Adults</subject><subject>Anesthesiology</subject><subject>Anticoagulants</subject><subject>Aptamers</subject><subject>Aptamers, Nucleotide - chemistry</subject><subject>Biology and Life Sciences</subject><subject>Blood Coagulation</subject><subject>Blood Coagulation Tests</subject><subject>Calibration</subject><subject>Case-Control Studies</subject><subject>Coagulants - chemistry</subject><subject>Coagulation</subject><subject>Computer Simulation</subject><subject>Cord blood</subject><subject>Factor IXa - antagonists & inhibitors</subject><subject>Female</subject><subject>Fetal Blood - metabolism</subject><subject>Genetic aspects</subject><subject>Gynecology</subject><subject>Hemostasis</subject><subject>Hemostatics</subject><subject>Humans</subject><subject>Inhibitors</subject><subject>Mathematical models</subject><subject>Medicine and Health Sciences</subject><subject>Models, Statistical</subject><subject>Models, Theoretical</subject><subject>Neonates</subject><subject>Newborn babies</subject><subject>Obstetrics</subject><subject>People and Places</subject><subject>Physiological aspects</subject><subject>Plasma - 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Academic</collection><collection>PubMed Central (Full Participant titles)</collection><collection>DOAJ Directory of Open Access Journals</collection><jtitle>PloS one</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Rice, Nicklaus T</au><au>Szlam, Fania</au><au>Varner, Jeffrey D</au><au>Bernstein, Peter S</au><au>Szlam, Arthur D</au><au>Tanaka, Kenichi A</au><au>Kanellopoulos-Langevin, Colette</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Differential Contributions of Intrinsic and Extrinsic Pathways to Thrombin Generation in Adult, Maternal and Cord Plasma Samples</atitle><jtitle>PloS one</jtitle><addtitle>PLoS One</addtitle><date>2016-05-19</date><risdate>2016</risdate><volume>11</volume><issue>5</issue><spage>e0154127</spage><epage>e0154127</epage><pages>e0154127-e0154127</pages><issn>1932-6203</issn><eissn>1932-6203</eissn><abstract>Thrombin generation (TG) is a pivotal process in achieving hemostasis. Coagulation profiles during pregnancy and early neonatal period are different from that of normal (non-pregnant) adults. In this ex vivo study, the differences in TG in maternal and cord plasma relative to normal adult plasma were studied.
Twenty consented pregnant women and ten consented healthy adults were included in the study. Maternal and cord blood samples were collected at the time of delivery. Platelet-poor plasma was isolated for the measurement of TG. In some samples, anti-FIXa aptamer, RB006, or a TFPI inhibitor, BAX499 were added to elucidate the contribution of intrinsic and extrinsic pathway to TG. Additionally, procoagulant and inhibitor levels were measured in maternal and cord plasma, and these values were used to mathematically simulate TG.
Peak TG was increased in maternal plasma (393.6±57.9 nM) compared to adult and cord samples (323.2±38.9 nM and 209.9±29.5 nM, respectively). Inhibitory effects of RB006 on TG were less robust in maternal or cord plasma (52% vs. 12% respectively) than in adult plasma (81%). Likewise the effectiveness of BAX499 as represented by the increase in peak TG was much greater in adult (21%) than in maternal (10%) or cord plasma (12%). Further, BAX499 was more effective in reversing RB006 in adult plasma than in maternal or cord plasma. Ex vivo data were reproducible with the results of the mathematical simulation of TG.
Normal parturient plasma shows a large intrinsic pathway reserve for TG compared to adult and cord plasma, while TG in cord plasma is sustained by extrinsic pathway, and low levels of TFPI and AT.</abstract><cop>United States</cop><pub>Public Library of Science</pub><pmid>27196067</pmid><doi>10.1371/journal.pone.0154127</doi><oa>free_for_read</oa></addata></record> |
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| subjects | Adult Adults Anesthesiology Anticoagulants Aptamers Aptamers, Nucleotide - chemistry Biology and Life Sciences Blood Coagulation Blood Coagulation Tests Calibration Case-Control Studies Coagulants - chemistry Coagulation Computer Simulation Cord blood Factor IXa - antagonists & inhibitors Female Fetal Blood - metabolism Genetic aspects Gynecology Hemostasis Hemostatics Humans Inhibitors Mathematical models Medicine and Health Sciences Models, Statistical Models, Theoretical Neonates Newborn babies Obstetrics People and Places Physiological aspects Plasma - metabolism Pregnancy Research and Analysis Methods Reversing Review boards Robustness (mathematics) Thrombin Thrombin - biosynthesis Thrombosis Young Adult |
| title | Differential Contributions of Intrinsic and Extrinsic Pathways to Thrombin Generation in Adult, Maternal and Cord Plasma Samples |
| url | https://sfx.bib-bvb.de/sfx_tum?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&ctx_tim=2025-01-26T04%3A10%3A02IST&url_ver=Z39.88-2004&url_ctx_fmt=infofi/fmt:kev:mtx:ctx&rfr_id=info:sid/primo.exlibrisgroup.com:primo3-Article-gale_plos_&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.atitle=Differential%20Contributions%20of%20Intrinsic%20and%20Extrinsic%20Pathways%20to%20Thrombin%20Generation%20in%20Adult,%20Maternal%20and%20Cord%20Plasma%20Samples&rft.jtitle=PloS%20one&rft.au=Rice,%20Nicklaus%20T&rft.date=2016-05-19&rft.volume=11&rft.issue=5&rft.spage=e0154127&rft.epage=e0154127&rft.pages=e0154127-e0154127&rft.issn=1932-6203&rft.eissn=1932-6203&rft_id=info:doi/10.1371/journal.pone.0154127&rft_dat=%3Cgale_plos_%3EA453360136%3C/gale_plos_%3E%3Curl%3E%3C/url%3E&disable_directlink=true&sfx.directlink=off&sfx.report_link=0&rft_id=info:oai/&rft_pqid=1790067321&rft_id=info:pmid/27196067&rft_galeid=A453360136&rft_doaj_id=oai_doaj_org_article_c9f837031dca48cfa2152c958921c897&rfr_iscdi=true |