Euglobulin clot lysis time reveals a high frequency of fibrinolytic activation in trauma
Activation of the fibrinolytic system plays a central role in the host response to trauma. There is significant heterogeneity in the degree of fibrinolysis activation at baseline that is usually assessed by whole blood thromboelastography (TEG). Few studies have focused on plasma markers of fibrinol...
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| Veröffentlicht in: | Thrombosis research 2021-08, Vol.204, p.22-28 |
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| creator | Ilich, Anton Kumar, Vaibhav Ferrara, Michael J. Henderson, Michael W. Noubouossie, Denis F. Jenkins, Donald H. Kozar, Rosemary A. Park, Myung S. Key, Nigel S. |
| description | Activation of the fibrinolytic system plays a central role in the host response to trauma. There is significant heterogeneity in the degree of fibrinolysis activation at baseline that is usually assessed by whole blood thromboelastography (TEG). Few studies have focused on plasma markers of fibrinolysis that could add novel insights into the frequency and mechanisms of fibrinolytic activation in trauma. Global fibrinolysis in plasma was assessed using a modified euglobulin clot lysis time (ECLT) assay in 171 major trauma patients and compared to commonly assessed analytes of fibrinolysis. The median ECLT in trauma patients was significantly shorter at 8.5 h (IQR, 1.3–19.5) compared to 19.9 h (9.8–22.6) in healthy controls (p |
| doi_str_mv | 10.1016/j.thromres.2021.05.017 |
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•The euglobulin clot lysis time (ECLT) detects a high frequency of hyperfibrinolysis in trauma•A hyperfibrinolytic ECLT profile is associated with elevated free tPA, PAP and D-dimer levels•ECLT, D-dimer, tPA and PAP are associated with the need for massive transfusion</description><identifier>ISSN: 0049-3848</identifier><identifier>EISSN: 1879-2472</identifier><identifier>DOI: 10.1016/j.thromres.2021.05.017</identifier><identifier>PMID: 34111811</identifier><language>eng</language><publisher>Elsevier Ltd</publisher><subject>D-dimer ; Euglobulin clot lysis time ; Fibrinolysis ; Plasmin-antiplasmin complexes ; Tissue plasminogen activator ; Trauma</subject><ispartof>Thrombosis research, 2021-08, Vol.204, p.22-28</ispartof><rights>2021 Elsevier Ltd</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c514t-33dcb9da4d613b4093c85a56c09c6514cd457bac8e923c753105a908178be66e3</citedby><cites>FETCH-LOGICAL-c514t-33dcb9da4d613b4093c85a56c09c6514cd457bac8e923c753105a908178be66e3</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktohtml>$$Uhttps://www.sciencedirect.com/science/article/pii/S0049384821003480$$EHTML$$P50$$Gelsevier$$H</linktohtml><link.rule.ids>230,314,776,780,881,3537,27901,27902,65306</link.rule.ids></links><search><creatorcontrib>Ilich, Anton</creatorcontrib><creatorcontrib>Kumar, Vaibhav</creatorcontrib><creatorcontrib>Ferrara, Michael J.</creatorcontrib><creatorcontrib>Henderson, Michael W.</creatorcontrib><creatorcontrib>Noubouossie, Denis F.</creatorcontrib><creatorcontrib>Jenkins, Donald H.</creatorcontrib><creatorcontrib>Kozar, Rosemary A.</creatorcontrib><creatorcontrib>Park, Myung S.</creatorcontrib><creatorcontrib>Key, Nigel S.</creatorcontrib><title>Euglobulin clot lysis time reveals a high frequency of fibrinolytic activation in trauma</title><title>Thrombosis research</title><description>Activation of the fibrinolytic system plays a central role in the host response to trauma. There is significant heterogeneity in the degree of fibrinolysis activation at baseline that is usually assessed by whole blood thromboelastography (TEG). Few studies have focused on plasma markers of fibrinolysis that could add novel insights into the frequency and mechanisms of fibrinolytic activation in trauma. Global fibrinolysis in plasma was assessed using a modified euglobulin clot lysis time (ECLT) assay in 171 major trauma patients and compared to commonly assessed analytes of fibrinolysis. The median ECLT in trauma patients was significantly shorter at 8.5 h (IQR, 1.3–19.5) compared to 19.9 h (9.8–22.6) in healthy controls (p < 0.0001). ECLT values ≤2.5th percentile of the reference range were present in 83 (48.5%) of trauma patients, suggesting increased fibrinolytic activation. Shortened ECLT values were associated with elevated plasmin-antiplasmin (PAP) complexes and free tissue plasminogen activator (tPA) levels in plasma. Sixteen (9.2%) individuals met the primary outcome for massive transfusion, here defined as the critical administration threshold (CAT) of 3 units of packed red cells in any 60-minute period within the first 24 h. In a univariate screen, plasma biomarkers associated with CAT included D-dimer (p < 0.001), PAP (p < 0.05), free tPA (p < 0.05) and ECLT (p < 0.05). We conclude that fibrinolytic activation, measured by ECLT, is present in a high proportion of trauma patients at presentation. The shortened ECLT is partially driven by high tPA levels and is associated with high levels of circulating PAP complexes. Further studies are needed to determine whether ECLT is an independent predictor of trauma outcomes.
•The euglobulin clot lysis time (ECLT) detects a high frequency of hyperfibrinolysis in trauma•A hyperfibrinolytic ECLT profile is associated with elevated free tPA, PAP and D-dimer levels•ECLT, D-dimer, tPA and PAP are associated with the need for massive transfusion</description><subject>D-dimer</subject><subject>Euglobulin clot lysis time</subject><subject>Fibrinolysis</subject><subject>Plasmin-antiplasmin complexes</subject><subject>Tissue plasminogen activator</subject><subject>Trauma</subject><issn>0049-3848</issn><issn>1879-2472</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2021</creationdate><recordtype>article</recordtype><recordid>eNqFkUFr3DAQhUVpaTZp_0LRsRe7kiVZ0qW0hCQtBHppIDchy-NdLbKVSvLC_vto2bTQU05zmPe-Yd5D6BMlLSW0_7Jvyy7FOUFuO9LRloiWUPkGbaiSuum47N6iDSFcN0xxdYEuc96TqqBavEcXjFNKFaUb9HizbkMc1uAX7EIsOByzz7j4GXCCA9iQscU7v93hKcGfFRZ3xHHCkx-SX2I4Fu-wdcUfbPFxwRVTkl1n-wG9m6oZPr7MK_Rwe_P7-kdz_-vu5_X3-8YJykvD2OgGPVo-9pQNnGjmlLCid0S7vircyIUcrFOgO-akYJQIq4miUg3Q98Cu0Ncz92kdZhgdLPV-ME_JzzYdTbTe_L9Z_M5s48GoTkrJ-wr4_AJIsf6Xi5l9dhCCXSCu2XSCE0Flr0_S_ix1KeacYPp3hhJzqsXszd9azKkWQ4SpoVfjt7MRahIHD8lk52uUMPoErpgx-tcQzzPvmrI</recordid><startdate>20210801</startdate><enddate>20210801</enddate><creator>Ilich, Anton</creator><creator>Kumar, Vaibhav</creator><creator>Ferrara, Michael J.</creator><creator>Henderson, Michael W.</creator><creator>Noubouossie, Denis F.</creator><creator>Jenkins, Donald H.</creator><creator>Kozar, Rosemary A.</creator><creator>Park, Myung S.</creator><creator>Key, Nigel S.</creator><general>Elsevier Ltd</general><scope>AAYXX</scope><scope>CITATION</scope><scope>7X8</scope><scope>5PM</scope></search><sort><creationdate>20210801</creationdate><title>Euglobulin clot lysis time reveals a high frequency of fibrinolytic activation in trauma</title><author>Ilich, Anton ; Kumar, Vaibhav ; Ferrara, Michael J. ; Henderson, Michael W. ; Noubouossie, Denis F. ; Jenkins, Donald H. ; Kozar, Rosemary A. ; Park, Myung S. ; Key, Nigel S.</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c514t-33dcb9da4d613b4093c85a56c09c6514cd457bac8e923c753105a908178be66e3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2021</creationdate><topic>D-dimer</topic><topic>Euglobulin clot lysis time</topic><topic>Fibrinolysis</topic><topic>Plasmin-antiplasmin complexes</topic><topic>Tissue plasminogen activator</topic><topic>Trauma</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Ilich, Anton</creatorcontrib><creatorcontrib>Kumar, Vaibhav</creatorcontrib><creatorcontrib>Ferrara, Michael J.</creatorcontrib><creatorcontrib>Henderson, Michael W.</creatorcontrib><creatorcontrib>Noubouossie, Denis F.</creatorcontrib><creatorcontrib>Jenkins, Donald H.</creatorcontrib><creatorcontrib>Kozar, Rosemary A.</creatorcontrib><creatorcontrib>Park, Myung S.</creatorcontrib><creatorcontrib>Key, Nigel S.</creatorcontrib><collection>CrossRef</collection><collection>MEDLINE - Academic</collection><collection>PubMed Central (Full Participant titles)</collection><jtitle>Thrombosis research</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Ilich, Anton</au><au>Kumar, Vaibhav</au><au>Ferrara, Michael J.</au><au>Henderson, Michael W.</au><au>Noubouossie, Denis F.</au><au>Jenkins, Donald H.</au><au>Kozar, Rosemary A.</au><au>Park, Myung S.</au><au>Key, Nigel S.</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Euglobulin clot lysis time reveals a high frequency of fibrinolytic activation in trauma</atitle><jtitle>Thrombosis research</jtitle><date>2021-08-01</date><risdate>2021</risdate><volume>204</volume><spage>22</spage><epage>28</epage><pages>22-28</pages><issn>0049-3848</issn><eissn>1879-2472</eissn><abstract>Activation of the fibrinolytic system plays a central role in the host response to trauma. There is significant heterogeneity in the degree of fibrinolysis activation at baseline that is usually assessed by whole blood thromboelastography (TEG). Few studies have focused on plasma markers of fibrinolysis that could add novel insights into the frequency and mechanisms of fibrinolytic activation in trauma. Global fibrinolysis in plasma was assessed using a modified euglobulin clot lysis time (ECLT) assay in 171 major trauma patients and compared to commonly assessed analytes of fibrinolysis. The median ECLT in trauma patients was significantly shorter at 8.5 h (IQR, 1.3–19.5) compared to 19.9 h (9.8–22.6) in healthy controls (p < 0.0001). ECLT values ≤2.5th percentile of the reference range were present in 83 (48.5%) of trauma patients, suggesting increased fibrinolytic activation. Shortened ECLT values were associated with elevated plasmin-antiplasmin (PAP) complexes and free tissue plasminogen activator (tPA) levels in plasma. Sixteen (9.2%) individuals met the primary outcome for massive transfusion, here defined as the critical administration threshold (CAT) of 3 units of packed red cells in any 60-minute period within the first 24 h. In a univariate screen, plasma biomarkers associated with CAT included D-dimer (p < 0.001), PAP (p < 0.05), free tPA (p < 0.05) and ECLT (p < 0.05). We conclude that fibrinolytic activation, measured by ECLT, is present in a high proportion of trauma patients at presentation. The shortened ECLT is partially driven by high tPA levels and is associated with high levels of circulating PAP complexes. Further studies are needed to determine whether ECLT is an independent predictor of trauma outcomes.
•The euglobulin clot lysis time (ECLT) detects a high frequency of hyperfibrinolysis in trauma•A hyperfibrinolytic ECLT profile is associated with elevated free tPA, PAP and D-dimer levels•ECLT, D-dimer, tPA and PAP are associated with the need for massive transfusion</abstract><pub>Elsevier Ltd</pub><pmid>34111811</pmid><doi>10.1016/j.thromres.2021.05.017</doi><tpages>7</tpages><oa>free_for_read</oa></addata></record> |
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| subjects | D-dimer Euglobulin clot lysis time Fibrinolysis Plasmin-antiplasmin complexes Tissue plasminogen activator Trauma |
| title | Euglobulin clot lysis time reveals a high frequency of fibrinolytic activation in trauma |
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