Therapeutic versus prophylactic anticoagulation for severe COVID-19: A randomized phase II clinical trial (HESACOVID)
Coronavirus disease 2019 (COVID-19) causes a hypercoagulable state. Several autopsy studies have found microthrombi in pulmonary circulation. In this randomized, open-label, phase II study, we randomized COVID-19 patients requiring mechanical ventilation to receive either therapeutic enoxaparin or t...
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| Veröffentlicht in: | Thrombosis research 2020-12, Vol.196, p.359-366 |
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| creator | Lemos, Anna Cristina Bertoldi do Espírito Santo, Douglas Alexandre Salvetti, Maísa Cabetti Gilio, Renato Noffs Agra, Lucas Barbosa Pazin-Filho, Antonio Miranda, Carlos Henrique |
| description | Coronavirus disease 2019 (COVID-19) causes a hypercoagulable state. Several autopsy studies have found microthrombi in pulmonary circulation.
In this randomized, open-label, phase II study, we randomized COVID-19 patients requiring mechanical ventilation to receive either therapeutic enoxaparin or the standard anticoagulant thromboprophylaxis. We evaluated the gas exchange over time through the ratio of partial pressure of arterial oxygen (PaO2) to the fraction of inspired oxygen (FiO2) at baseline, 7, and 14 days after randomization, the time until successful liberation from mechanical ventilation, and the ventilator-free days.
Ten patients were assigned to the therapeutic enoxaparin and ten patients to prophylactic anticoagulation. There was a statistically significant increase in the PaO2/FiO2 ratio over time in the therapeutic group (163 [95% confidence interval – CI 133–193] at baseline, 209 [95% CI 171–247] after 7 days, and 261 [95% CI 230–293] after 14 days), p = 0.0004. In contrast, we did not observe this improvement over time in the prophylactic group (184 [95% CI 146–222] at baseline, 168 [95% CI 142–195] after 7 days, and 195 [95% CI 128–262] after 14 days), p = 0.487. Patients of the therapeutic group had a higher ratio of successful liberation from mechanical ventilation (hazard ratio: 4.0 [95% CI 1.035–15.053]), p = 0.031 and more ventilator-free days (15 days [interquartile range IQR 6–16] versus 0 days [IQR 0–11]), p = 0.028 when compared to the prophylactic group.
Therapeutic enoxaparin improves gas exchange and decreases the need for mechanical ventilation in severe COVID–19.
REBEC RBR-949z6v.
•COVID-19 is associated with microthrombi in pulmonary circulation.•We randomized severe COVID-19 patients to receive either therapeutic enoxaparin or the standard thromboprophylaxis.•Therapeutic enoxaparin resulted in improved gas exchange over time.•Larger clinical trial is urgently needed to evaluate the anticoagulant therapy in severe COVID-19. |
| doi_str_mv | 10.1016/j.thromres.2020.09.026 |
| format | Article |
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In this randomized, open-label, phase II study, we randomized COVID-19 patients requiring mechanical ventilation to receive either therapeutic enoxaparin or the standard anticoagulant thromboprophylaxis. We evaluated the gas exchange over time through the ratio of partial pressure of arterial oxygen (PaO2) to the fraction of inspired oxygen (FiO2) at baseline, 7, and 14 days after randomization, the time until successful liberation from mechanical ventilation, and the ventilator-free days.
Ten patients were assigned to the therapeutic enoxaparin and ten patients to prophylactic anticoagulation. There was a statistically significant increase in the PaO2/FiO2 ratio over time in the therapeutic group (163 [95% confidence interval – CI 133–193] at baseline, 209 [95% CI 171–247] after 7 days, and 261 [95% CI 230–293] after 14 days), p = 0.0004. In contrast, we did not observe this improvement over time in the prophylactic group (184 [95% CI 146–222] at baseline, 168 [95% CI 142–195] after 7 days, and 195 [95% CI 128–262] after 14 days), p = 0.487. Patients of the therapeutic group had a higher ratio of successful liberation from mechanical ventilation (hazard ratio: 4.0 [95% CI 1.035–15.053]), p = 0.031 and more ventilator-free days (15 days [interquartile range IQR 6–16] versus 0 days [IQR 0–11]), p = 0.028 when compared to the prophylactic group.
Therapeutic enoxaparin improves gas exchange and decreases the need for mechanical ventilation in severe COVID–19.
REBEC RBR-949z6v.
•COVID-19 is associated with microthrombi in pulmonary circulation.•We randomized severe COVID-19 patients to receive either therapeutic enoxaparin or the standard thromboprophylaxis.•Therapeutic enoxaparin resulted in improved gas exchange over time.•Larger clinical trial is urgently needed to evaluate the anticoagulant therapy in severe COVID-19.</description><identifier>ISSN: 0049-3848</identifier><identifier>EISSN: 1879-2472</identifier><identifier>DOI: 10.1016/j.thromres.2020.09.026</identifier><identifier>PMID: 32977137</identifier><language>eng</language><publisher>United States: Elsevier Ltd</publisher><subject>Adult ; Aged ; Anticoagulant treatment ; Anticoagulants - administration & dosage ; Brazil ; Coagulopathy ; COVID-19 ; COVID-19 - complications ; COVID-19 - diagnosis ; COVID-19 - drug therapy ; COVID-19 - physiopathology ; D-dimer ; Drug Administration Schedule ; Enoxaparin - administration & dosage ; Female ; Full Length ; Humans ; Lung - drug effects ; Lung - physiopathology ; Male ; Mechanical ventilation ; Middle Aged ; Pulmonary Gas Exchange - drug effects ; Respiration, Artificial ; Thrombophilia - diagnosis ; Thrombophilia - etiology ; Thrombophilia - prevention & control ; Thrombosis - diagnosis ; Thrombosis - etiology ; Thrombosis - prevention & control ; Time Factors ; Treatment Outcome</subject><ispartof>Thrombosis research, 2020-12, Vol.196, p.359-366</ispartof><rights>2020</rights><rights>Copyright © 2020. Published by Elsevier Ltd.</rights><rights>2020 Elsevier Ltd. All rights reserved. 2020</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c537t-a7d527b15833332e951efd481ec144d734419d9ff88c3745d5a21e34dbc936863</citedby><cites>FETCH-LOGICAL-c537t-a7d527b15833332e951efd481ec144d734419d9ff88c3745d5a21e34dbc936863</cites><orcidid>0000-0002-5968-4879</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktohtml>$$Uhttps://dx.doi.org/10.1016/j.thromres.2020.09.026$$EHTML$$P50$$Gelsevier$$H</linktohtml><link.rule.ids>230,314,780,784,885,3550,27924,27925,45995</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/32977137$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Lemos, Anna Cristina Bertoldi</creatorcontrib><creatorcontrib>do Espírito Santo, Douglas Alexandre</creatorcontrib><creatorcontrib>Salvetti, Maísa Cabetti</creatorcontrib><creatorcontrib>Gilio, Renato Noffs</creatorcontrib><creatorcontrib>Agra, Lucas Barbosa</creatorcontrib><creatorcontrib>Pazin-Filho, Antonio</creatorcontrib><creatorcontrib>Miranda, Carlos Henrique</creatorcontrib><title>Therapeutic versus prophylactic anticoagulation for severe COVID-19: A randomized phase II clinical trial (HESACOVID)</title><title>Thrombosis research</title><addtitle>Thromb Res</addtitle><description>Coronavirus disease 2019 (COVID-19) causes a hypercoagulable state. Several autopsy studies have found microthrombi in pulmonary circulation.
In this randomized, open-label, phase II study, we randomized COVID-19 patients requiring mechanical ventilation to receive either therapeutic enoxaparin or the standard anticoagulant thromboprophylaxis. We evaluated the gas exchange over time through the ratio of partial pressure of arterial oxygen (PaO2) to the fraction of inspired oxygen (FiO2) at baseline, 7, and 14 days after randomization, the time until successful liberation from mechanical ventilation, and the ventilator-free days.
Ten patients were assigned to the therapeutic enoxaparin and ten patients to prophylactic anticoagulation. There was a statistically significant increase in the PaO2/FiO2 ratio over time in the therapeutic group (163 [95% confidence interval – CI 133–193] at baseline, 209 [95% CI 171–247] after 7 days, and 261 [95% CI 230–293] after 14 days), p = 0.0004. In contrast, we did not observe this improvement over time in the prophylactic group (184 [95% CI 146–222] at baseline, 168 [95% CI 142–195] after 7 days, and 195 [95% CI 128–262] after 14 days), p = 0.487. Patients of the therapeutic group had a higher ratio of successful liberation from mechanical ventilation (hazard ratio: 4.0 [95% CI 1.035–15.053]), p = 0.031 and more ventilator-free days (15 days [interquartile range IQR 6–16] versus 0 days [IQR 0–11]), p = 0.028 when compared to the prophylactic group.
Therapeutic enoxaparin improves gas exchange and decreases the need for mechanical ventilation in severe COVID–19.
REBEC RBR-949z6v.
•COVID-19 is associated with microthrombi in pulmonary circulation.•We randomized severe COVID-19 patients to receive either therapeutic enoxaparin or the standard thromboprophylaxis.•Therapeutic enoxaparin resulted in improved gas exchange over time.•Larger clinical trial is urgently needed to evaluate the anticoagulant therapy in severe COVID-19.</description><subject>Adult</subject><subject>Aged</subject><subject>Anticoagulant treatment</subject><subject>Anticoagulants - administration & dosage</subject><subject>Brazil</subject><subject>Coagulopathy</subject><subject>COVID-19</subject><subject>COVID-19 - complications</subject><subject>COVID-19 - diagnosis</subject><subject>COVID-19 - drug therapy</subject><subject>COVID-19 - physiopathology</subject><subject>D-dimer</subject><subject>Drug Administration Schedule</subject><subject>Enoxaparin - administration & dosage</subject><subject>Female</subject><subject>Full Length</subject><subject>Humans</subject><subject>Lung - drug effects</subject><subject>Lung - physiopathology</subject><subject>Male</subject><subject>Mechanical ventilation</subject><subject>Middle Aged</subject><subject>Pulmonary Gas Exchange - drug effects</subject><subject>Respiration, Artificial</subject><subject>Thrombophilia - diagnosis</subject><subject>Thrombophilia - etiology</subject><subject>Thrombophilia - prevention & control</subject><subject>Thrombosis - diagnosis</subject><subject>Thrombosis - etiology</subject><subject>Thrombosis - prevention & control</subject><subject>Time Factors</subject><subject>Treatment Outcome</subject><issn>0049-3848</issn><issn>1879-2472</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2020</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNqFkU9v1DAQxS0EotvCV6h8LIcE_0scc0CslpauVKkHClfLa08ar7JxsJOV2k-Pl20rOOHDWBr_3puRH0LnlJSU0Prjtpy6GHYRUskIIyVRJWH1K7SgjVQFE5K9RgtChCp4I5oTdJrSlhAqqareohPOlJSUywWa7zqIZoR58hbvIaY54TGGsXvojT30zJBrMPdzbyYfBtyGiBNkEvDq9uf6a0HVJ7zE0Qwu7PwjODx2JgFer7Ht_eCt6fEUfa4X15ffl380H96hN63pE7x_us_Qj6vLu9V1cXP7bb1a3hS24nIqjHQVkxtaNTwfBqqi0DrRULBUCCe5EFQ51bZNY7kUlasMo8CF21jF66bmZ-jz0XecNztwFoYpml6P0e9MfNDBeP3vy-A7fR_2WlaEk1plg4sngxh-zZAmvfPJQt-bAcKcNBOiriXhsspofURtDClFaF_GUKIPmemtfs5MHzLTROmcWRae_73ki-w5pAx8OQKQv2rvIepkPQwWnI9gJ-2C_9-M318ZrI8</recordid><startdate>20201201</startdate><enddate>20201201</enddate><creator>Lemos, Anna Cristina Bertoldi</creator><creator>do Espírito Santo, Douglas Alexandre</creator><creator>Salvetti, Maísa Cabetti</creator><creator>Gilio, Renato Noffs</creator><creator>Agra, Lucas Barbosa</creator><creator>Pazin-Filho, Antonio</creator><creator>Miranda, Carlos Henrique</creator><general>Elsevier Ltd</general><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>7X8</scope><scope>5PM</scope><orcidid>https://orcid.org/0000-0002-5968-4879</orcidid></search><sort><creationdate>20201201</creationdate><title>Therapeutic versus prophylactic anticoagulation for severe COVID-19: A randomized phase II clinical trial (HESACOVID)</title><author>Lemos, Anna Cristina Bertoldi ; do Espírito Santo, Douglas Alexandre ; Salvetti, Maísa Cabetti ; Gilio, Renato Noffs ; Agra, Lucas Barbosa ; Pazin-Filho, Antonio ; Miranda, Carlos Henrique</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c537t-a7d527b15833332e951efd481ec144d734419d9ff88c3745d5a21e34dbc936863</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2020</creationdate><topic>Adult</topic><topic>Aged</topic><topic>Anticoagulant treatment</topic><topic>Anticoagulants - administration & dosage</topic><topic>Brazil</topic><topic>Coagulopathy</topic><topic>COVID-19</topic><topic>COVID-19 - complications</topic><topic>COVID-19 - diagnosis</topic><topic>COVID-19 - drug therapy</topic><topic>COVID-19 - physiopathology</topic><topic>D-dimer</topic><topic>Drug Administration Schedule</topic><topic>Enoxaparin - administration & dosage</topic><topic>Female</topic><topic>Full Length</topic><topic>Humans</topic><topic>Lung - drug effects</topic><topic>Lung - physiopathology</topic><topic>Male</topic><topic>Mechanical ventilation</topic><topic>Middle Aged</topic><topic>Pulmonary Gas Exchange - drug effects</topic><topic>Respiration, Artificial</topic><topic>Thrombophilia - diagnosis</topic><topic>Thrombophilia - etiology</topic><topic>Thrombophilia - prevention & control</topic><topic>Thrombosis - diagnosis</topic><topic>Thrombosis - etiology</topic><topic>Thrombosis - prevention & control</topic><topic>Time Factors</topic><topic>Treatment Outcome</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Lemos, Anna Cristina Bertoldi</creatorcontrib><creatorcontrib>do Espírito Santo, Douglas Alexandre</creatorcontrib><creatorcontrib>Salvetti, Maísa Cabetti</creatorcontrib><creatorcontrib>Gilio, Renato Noffs</creatorcontrib><creatorcontrib>Agra, Lucas Barbosa</creatorcontrib><creatorcontrib>Pazin-Filho, Antonio</creatorcontrib><creatorcontrib>Miranda, Carlos Henrique</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><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>Lemos, Anna Cristina Bertoldi</au><au>do Espírito Santo, Douglas Alexandre</au><au>Salvetti, Maísa Cabetti</au><au>Gilio, Renato Noffs</au><au>Agra, Lucas Barbosa</au><au>Pazin-Filho, Antonio</au><au>Miranda, Carlos Henrique</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Therapeutic versus prophylactic anticoagulation for severe COVID-19: A randomized phase II clinical trial (HESACOVID)</atitle><jtitle>Thrombosis research</jtitle><addtitle>Thromb Res</addtitle><date>2020-12-01</date><risdate>2020</risdate><volume>196</volume><spage>359</spage><epage>366</epage><pages>359-366</pages><issn>0049-3848</issn><eissn>1879-2472</eissn><abstract>Coronavirus disease 2019 (COVID-19) causes a hypercoagulable state. Several autopsy studies have found microthrombi in pulmonary circulation.
In this randomized, open-label, phase II study, we randomized COVID-19 patients requiring mechanical ventilation to receive either therapeutic enoxaparin or the standard anticoagulant thromboprophylaxis. We evaluated the gas exchange over time through the ratio of partial pressure of arterial oxygen (PaO2) to the fraction of inspired oxygen (FiO2) at baseline, 7, and 14 days after randomization, the time until successful liberation from mechanical ventilation, and the ventilator-free days.
Ten patients were assigned to the therapeutic enoxaparin and ten patients to prophylactic anticoagulation. There was a statistically significant increase in the PaO2/FiO2 ratio over time in the therapeutic group (163 [95% confidence interval – CI 133–193] at baseline, 209 [95% CI 171–247] after 7 days, and 261 [95% CI 230–293] after 14 days), p = 0.0004. In contrast, we did not observe this improvement over time in the prophylactic group (184 [95% CI 146–222] at baseline, 168 [95% CI 142–195] after 7 days, and 195 [95% CI 128–262] after 14 days), p = 0.487. Patients of the therapeutic group had a higher ratio of successful liberation from mechanical ventilation (hazard ratio: 4.0 [95% CI 1.035–15.053]), p = 0.031 and more ventilator-free days (15 days [interquartile range IQR 6–16] versus 0 days [IQR 0–11]), p = 0.028 when compared to the prophylactic group.
Therapeutic enoxaparin improves gas exchange and decreases the need for mechanical ventilation in severe COVID–19.
REBEC RBR-949z6v.
•COVID-19 is associated with microthrombi in pulmonary circulation.•We randomized severe COVID-19 patients to receive either therapeutic enoxaparin or the standard thromboprophylaxis.•Therapeutic enoxaparin resulted in improved gas exchange over time.•Larger clinical trial is urgently needed to evaluate the anticoagulant therapy in severe COVID-19.</abstract><cop>United States</cop><pub>Elsevier Ltd</pub><pmid>32977137</pmid><doi>10.1016/j.thromres.2020.09.026</doi><tpages>8</tpages><orcidid>https://orcid.org/0000-0002-5968-4879</orcidid><oa>free_for_read</oa></addata></record> |
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| source | MEDLINE; Access via ScienceDirect (Elsevier) |
| subjects | Adult Aged Anticoagulant treatment Anticoagulants - administration & dosage Brazil Coagulopathy COVID-19 COVID-19 - complications COVID-19 - diagnosis COVID-19 - drug therapy COVID-19 - physiopathology D-dimer Drug Administration Schedule Enoxaparin - administration & dosage Female Full Length Humans Lung - drug effects Lung - physiopathology Male Mechanical ventilation Middle Aged Pulmonary Gas Exchange - drug effects Respiration, Artificial Thrombophilia - diagnosis Thrombophilia - etiology Thrombophilia - prevention & control Thrombosis - diagnosis Thrombosis - etiology Thrombosis - prevention & control Time Factors Treatment Outcome |
| title | Therapeutic versus prophylactic anticoagulation for severe COVID-19: A randomized phase II clinical trial (HESACOVID) |
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