Label-Free Kinetic Studies of Hemostasis-Related Biomarkers Including D-Dimer Using Autologous Serum Transfusion
The objective of this study was to evaluate the elimination kinetics of hemostasis-related biomarkers including the prothrombin activation fragment F1+2, thrombin-antithrombin complex (TAT), plasmin-α2-antiplasmin complex (PAP), and D-dimer in humans. Autologous serum was used as a biomarker source...
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| description | The objective of this study was to evaluate the elimination kinetics of hemostasis-related biomarkers including the prothrombin activation fragment F1+2, thrombin-antithrombin complex (TAT), plasmin-α2-antiplasmin complex (PAP), and D-dimer in humans. Autologous serum was used as a biomarker source and infused into 15 healthy volunteers. Serum was prepared from whole blood in the presence of recombinant tissue-type plasminogen activator (final concentration 20 μg/mL) to induce plasmin generation required for PAP and D-dimer formation. Serum transfusions (50 mL/30 min) were well tolerated by all subjects. Endogenous thrombin formation was not induced by serum infusions as measured using a highly sensitive oligonucleotide-based enzyme capture assay. Median peak levels (x-fold increase over baseline) of F1+2, TAT, PAP, and D-dimer of 3.7 nmol/L (28.9), 393 ng/mL (189.6), 3,829 ng/mL (7.0), and 13.4 mg/L (34.2) were achieved at the end of serum infusions. During a 48 h lasting follow-up period all biomarkers showed elimination kinetics of a two-compartment model. Median (interquartile range) terminal half-lives were 1.9 (1.3-3.6) h for F1+2, 0.7 (0.7-2.6) h for TAT, and 10.8 (8.8-11.4) h for PAP. With 15.8 (13.1-23.1) h the D-dimer half-life was about twice as long as previously estimated from radiolabeling studies in animals and small numbers of human subjects. The serum approach presented here allows label-free and simultaneous analysis of the elimination kinetics of various hemostasis-related biomarkers. Based on these data changes in biomarker levels could more precisely used to estimate the activity level of the hemostatic system. |
| doi_str_mv | 10.1371/journal.pone.0145012 |
| format | Article |
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Autologous serum was used as a biomarker source and infused into 15 healthy volunteers. Serum was prepared from whole blood in the presence of recombinant tissue-type plasminogen activator (final concentration 20 μg/mL) to induce plasmin generation required for PAP and D-dimer formation. Serum transfusions (50 mL/30 min) were well tolerated by all subjects. Endogenous thrombin formation was not induced by serum infusions as measured using a highly sensitive oligonucleotide-based enzyme capture assay. Median peak levels (x-fold increase over baseline) of F1+2, TAT, PAP, and D-dimer of 3.7 nmol/L (28.9), 393 ng/mL (189.6), 3,829 ng/mL (7.0), and 13.4 mg/L (34.2) were achieved at the end of serum infusions. During a 48 h lasting follow-up period all biomarkers showed elimination kinetics of a two-compartment model. Median (interquartile range) terminal half-lives were 1.9 (1.3-3.6) h for F1+2, 0.7 (0.7-2.6) h for TAT, and 10.8 (8.8-11.4) h for PAP. With 15.8 (13.1-23.1) h the D-dimer half-life was about twice as long as previously estimated from radiolabeling studies in animals and small numbers of human subjects. The serum approach presented here allows label-free and simultaneous analysis of the elimination kinetics of various hemostasis-related biomarkers. Based on these data changes in biomarker levels could more precisely used to estimate the activity level of the hemostatic system.</description><identifier>ISSN: 1932-6203</identifier><identifier>EISSN: 1932-6203</identifier><identifier>DOI: 10.1371/journal.pone.0145012</identifier><identifier>PMID: 26658824</identifier><language>eng</language><publisher>United States: Public Library of Science</publisher><subject>Adult ; Anticoagulants ; Antigens ; Antithrombin ; Biological markers ; Biomarkers ; Biomarkers - blood ; Blood & organ donations ; Blood transfusion ; Blood Transfusion, Autologous ; Enzyme kinetics ; Enzymes ; Female ; Fibrin Fibrinogen Degradation Products - analysis ; Fibrinolysis - drug effects ; Half life ; Healthy Volunteers ; Hematology ; Hemostasis ; Hemostatics ; Hepatitis ; Hospitals ; Humans ; Kinetics ; Life assessment ; Male ; Medicine ; Middle Aged ; Oligonucleotides ; Physiological aspects ; Plasmin ; Prospective Studies ; Protein research ; Prothrombin ; Radioactive half-life ; Studies ; Thrombin ; Thrombin - analysis ; Tissue Plasminogen Activator - pharmacology ; Transfusion ; Young Adult</subject><ispartof>PloS one, 2015-12, Vol.10 (12), p.e0145012-e0145012</ispartof><rights>COPYRIGHT 2015 Public Library of Science</rights><rights>2015 Rühl 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>2015 Rühl et al 2015 Rühl et al</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c758t-acfc53300bbc61017d1c3292903dda2d81b89121bc2ff67f7b0f00c9f6738c9d3</citedby><cites>FETCH-LOGICAL-c758t-acfc53300bbc61017d1c3292903dda2d81b89121bc2ff67f7b0f00c9f6738c9d3</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/PMC4684386/pdf/$$EPDF$$P50$$Gpubmedcentral$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC4684386/$$EHTML$$P50$$Gpubmedcentral$$Hfree_for_read</linktohtml><link.rule.ids>230,314,723,776,780,860,881,2096,2915,23845,27901,27902,53766,53768,79342,79343</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/26658824$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Rühl, Heiko</creatorcontrib><creatorcontrib>Berens, Christina</creatorcontrib><creatorcontrib>Winterhagen, Anna</creatorcontrib><creatorcontrib>Müller, Jens</creatorcontrib><creatorcontrib>Oldenburg, Johannes</creatorcontrib><creatorcontrib>Pötzsch, Bernd</creatorcontrib><title>Label-Free Kinetic Studies of Hemostasis-Related Biomarkers Including D-Dimer Using Autologous Serum Transfusion</title><title>PloS one</title><addtitle>PLoS One</addtitle><description>The objective of this study was to evaluate the elimination kinetics of hemostasis-related biomarkers including the prothrombin activation fragment F1+2, thrombin-antithrombin complex (TAT), plasmin-α2-antiplasmin complex (PAP), and D-dimer in humans. 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Based on these data changes in biomarker levels could more precisely used to estimate the activity level of the hemostatic system.</description><subject>Adult</subject><subject>Anticoagulants</subject><subject>Antigens</subject><subject>Antithrombin</subject><subject>Biological markers</subject><subject>Biomarkers</subject><subject>Biomarkers - blood</subject><subject>Blood & organ donations</subject><subject>Blood transfusion</subject><subject>Blood Transfusion, Autologous</subject><subject>Enzyme kinetics</subject><subject>Enzymes</subject><subject>Female</subject><subject>Fibrin Fibrinogen Degradation Products - analysis</subject><subject>Fibrinolysis - drug effects</subject><subject>Half life</subject><subject>Healthy Volunteers</subject><subject>Hematology</subject><subject>Hemostasis</subject><subject>Hemostatics</subject><subject>Hepatitis</subject><subject>Hospitals</subject><subject>Humans</subject><subject>Kinetics</subject><subject>Life assessment</subject><subject>Male</subject><subject>Medicine</subject><subject>Middle Aged</subject><subject>Oligonucleotides</subject><subject>Physiological aspects</subject><subject>Plasmin</subject><subject>Prospective Studies</subject><subject>Protein research</subject><subject>Prothrombin</subject><subject>Radioactive half-life</subject><subject>Studies</subject><subject>Thrombin</subject><subject>Thrombin - 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Autologous serum was used as a biomarker source and infused into 15 healthy volunteers. Serum was prepared from whole blood in the presence of recombinant tissue-type plasminogen activator (final concentration 20 μg/mL) to induce plasmin generation required for PAP and D-dimer formation. Serum transfusions (50 mL/30 min) were well tolerated by all subjects. Endogenous thrombin formation was not induced by serum infusions as measured using a highly sensitive oligonucleotide-based enzyme capture assay. Median peak levels (x-fold increase over baseline) of F1+2, TAT, PAP, and D-dimer of 3.7 nmol/L (28.9), 393 ng/mL (189.6), 3,829 ng/mL (7.0), and 13.4 mg/L (34.2) were achieved at the end of serum infusions. During a 48 h lasting follow-up period all biomarkers showed elimination kinetics of a two-compartment model. Median (interquartile range) terminal half-lives were 1.9 (1.3-3.6) h for F1+2, 0.7 (0.7-2.6) h for TAT, and 10.8 (8.8-11.4) h for PAP. With 15.8 (13.1-23.1) h the D-dimer half-life was about twice as long as previously estimated from radiolabeling studies in animals and small numbers of human subjects. The serum approach presented here allows label-free and simultaneous analysis of the elimination kinetics of various hemostasis-related biomarkers. Based on these data changes in biomarker levels could more precisely used to estimate the activity level of the hemostatic system.</abstract><cop>United States</cop><pub>Public Library of Science</pub><pmid>26658824</pmid><doi>10.1371/journal.pone.0145012</doi><oa>free_for_read</oa></addata></record> |
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| issn | 1932-6203 1932-6203 |
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| subjects | Adult Anticoagulants Antigens Antithrombin Biological markers Biomarkers Biomarkers - blood Blood & organ donations Blood transfusion Blood Transfusion, Autologous Enzyme kinetics Enzymes Female Fibrin Fibrinogen Degradation Products - analysis Fibrinolysis - drug effects Half life Healthy Volunteers Hematology Hemostasis Hemostatics Hepatitis Hospitals Humans Kinetics Life assessment Male Medicine Middle Aged Oligonucleotides Physiological aspects Plasmin Prospective Studies Protein research Prothrombin Radioactive half-life Studies Thrombin Thrombin - analysis Tissue Plasminogen Activator - pharmacology Transfusion Young Adult |
| title | Label-Free Kinetic Studies of Hemostasis-Related Biomarkers Including D-Dimer Using Autologous Serum Transfusion |
| url | https://sfx.bib-bvb.de/sfx_tum?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&ctx_tim=2025-02-13T01%3A56%3A08IST&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=Label-Free%20Kinetic%20Studies%20of%20Hemostasis-Related%20Biomarkers%20Including%20D-Dimer%20Using%20Autologous%20Serum%20Transfusion&rft.jtitle=PloS%20one&rft.au=R%C3%BChl,%20Heiko&rft.date=2015-12-14&rft.volume=10&rft.issue=12&rft.spage=e0145012&rft.epage=e0145012&rft.pages=e0145012-e0145012&rft.issn=1932-6203&rft.eissn=1932-6203&rft_id=info:doi/10.1371/journal.pone.0145012&rft_dat=%3Cgale_plos_%3EA437465996%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=1748864765&rft_id=info:pmid/26658824&rft_galeid=A437465996&rft_doaj_id=oai_doaj_org_article_a0ce7b88a52c4ce0a294915c452ebfbe&rfr_iscdi=true |