Safety and effectiveness of a four-factor prothrombin complex concentrate for vitamin K antagonist reversal following a fixed-dose strategy
ObjectivesEarly reversal of anticoagulation improves outcomes in major bleeding and emergency surgery. To reverse vitamin K antagonists (VKA), vitamin K in addition to prothrombin complex concentrate (PCC) is recommended. Dosing recommendations for VKA reversal provided by the manufacturer are 25–50...
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| Veröffentlicht in: | European journal of hospital pharmacy. Science and practice 2021-11, Vol.28 (e1), p.e66-e71 |
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| creator | Sobrino Jiménez, Carmen Romero-Garrido, José Antonio García-Martín, Ángeles Quintana-Díaz, Manuel Jiménez-Vicente, Carlos González-Del Valle, Luis Herrero Ambrosio, Alicia Benedí-González, Juana |
| description | ObjectivesEarly reversal of anticoagulation improves outcomes in major bleeding and emergency surgery. To reverse vitamin K antagonists (VKA), vitamin K in addition to prothrombin complex concentrate (PCC) is recommended. Dosing recommendations for VKA reversal provided by the manufacturer are 25–50 IU/kg depending on the baseline international normalised ratio (INR). Nevertheless, we recommend an initial fixed dose of 1000 IU, and additional 500 IU doses evaluated on a case-by-case basis. As there is a paucity of clinical data demonstrating the efficacy and safety of this strategy, we designed this study to assess the effectiveness and safety of a four-factor (4F)-PCC for VKA reversal following a fixed-dose strategy.MethodsThis was a retrospective study of adult patients who received 4F-PCC for VKA reversal. The primary outcome was INR correction. INR correction was achieved if the first INR draw after 4F-PCC was ≤1.5. Safety outcome was any confirmed thromboembolic event within 3 months after 4F-PCC. Secondary outcomes included activated partial thromboplastin time (aPTT) correction, as well as haemostatic effectiveness for bleeding patients.ResultsA total of 145 patients were included: 106 (73.1%) in the bleeding group and 39 (26.9%) in the emergency surgery group. The INR target was reached in 102 (70.3%) patients (p |
| doi_str_mv | 10.1136/ejhpharm-2019-002114 |
| format | Article |
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To reverse vitamin K antagonists (VKA), vitamin K in addition to prothrombin complex concentrate (PCC) is recommended. Dosing recommendations for VKA reversal provided by the manufacturer are 25–50 IU/kg depending on the baseline international normalised ratio (INR). Nevertheless, we recommend an initial fixed dose of 1000 IU, and additional 500 IU doses evaluated on a case-by-case basis. As there is a paucity of clinical data demonstrating the efficacy and safety of this strategy, we designed this study to assess the effectiveness and safety of a four-factor (4F)-PCC for VKA reversal following a fixed-dose strategy.MethodsThis was a retrospective study of adult patients who received 4F-PCC for VKA reversal. The primary outcome was INR correction. INR correction was achieved if the first INR draw after 4F-PCC was ≤1.5. Safety outcome was any confirmed thromboembolic event within 3 months after 4F-PCC. Secondary outcomes included activated partial thromboplastin time (aPTT) correction, as well as haemostatic effectiveness for bleeding patients.ResultsA total of 145 patients were included: 106 (73.1%) in the bleeding group and 39 (26.9%) in the emergency surgery group. The INR target was reached in 102 (70.3%) patients (p<0.0001). In one case, a thromboembolic complication was possibly related to 4F-PCC. The aPTT ratio target was reached in 113 (77.9%) patients (p<0.0001), and 79 of the 106 (74.5%) patients reversed for bleeding achieved haemostatic effectiveness.ConclusionsAfter 4F-PCC, the majority of patients achieved the target INR, meaning 4F-PCC is a useful modality for rapid INR reduction. The safety profile may be considered acceptable. Fixed-dose 4F-PCC was able to restore haemostasis rapidly while minimising the risk of adverse events and optimising available resources.</description><identifier>ISSN: 2047-9956</identifier><identifier>EISSN: 2047-9964</identifier><identifier>DOI: 10.1136/ejhpharm-2019-002114</identifier><identifier>PMID: 32591479</identifier><language>eng</language><publisher>England: British Medical Journal Publishing Group</publisher><subject>accident & emergency medicine ; Adult ; adverse effects ; Anticoagulants ; Anticoagulants - adverse effects ; anticoagulation ; bleeding disorders & coagulopathies ; Blood Coagulation Factors - adverse effects ; Clinical outcomes ; clinical pharmacy ; Drug administration ; Hemorrhage ; Humans ; intensive & critical care ; Original Research ; Patients ; Retrospective Studies ; Statistical analysis ; Surgery ; therapeutic drug monitoring ; Thromboembolism ; Vitamin K</subject><ispartof>European journal of hospital pharmacy. Science and practice, 2021-11, Vol.28 (e1), p.e66-e71</ispartof><rights>European Association of Hospital Pharmacists 2021. No commercial re-use. See rights and permissions. Published by BMJ.</rights><rights>European Association of Hospital Pharmacists 2020. No commercial re-use. See rights and permissions. Published by BMJ.</rights><rights>2021 European Association of Hospital Pharmacists 2021. No commercial re-use. See rights and permissions. Published by BMJ.</rights><rights>European Association of Hospital Pharmacists 2021. No commercial re-use. See rights and permissions. Published by BMJ. 2021</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-b517t-912c96ab2db516775c4ea59237c9622e06d8740a27887aeb33976ae8a0ecb3693</citedby><cites>FETCH-LOGICAL-b517t-912c96ab2db516775c4ea59237c9622e06d8740a27887aeb33976ae8a0ecb3693</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/PMC8640431/pdf/$$EPDF$$P50$$Gpubmedcentral$$H</linktopdf><linktohtml>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC8640431/$$EHTML$$P50$$Gpubmedcentral$$H</linktohtml><link.rule.ids>230,314,727,780,784,885,27923,27924,53790,53792</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/32591479$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Sobrino Jiménez, Carmen</creatorcontrib><creatorcontrib>Romero-Garrido, José Antonio</creatorcontrib><creatorcontrib>García-Martín, Ángeles</creatorcontrib><creatorcontrib>Quintana-Díaz, Manuel</creatorcontrib><creatorcontrib>Jiménez-Vicente, Carlos</creatorcontrib><creatorcontrib>González-Del Valle, Luis</creatorcontrib><creatorcontrib>Herrero Ambrosio, Alicia</creatorcontrib><creatorcontrib>Benedí-González, Juana</creatorcontrib><title>Safety and effectiveness of a four-factor prothrombin complex concentrate for vitamin K antagonist reversal following a fixed-dose strategy</title><title>European journal of hospital pharmacy. Science and practice</title><addtitle>Eur J Hosp Pharm</addtitle><addtitle>Eur J Hosp Pharm</addtitle><description>ObjectivesEarly reversal of anticoagulation improves outcomes in major bleeding and emergency surgery. To reverse vitamin K antagonists (VKA), vitamin K in addition to prothrombin complex concentrate (PCC) is recommended. Dosing recommendations for VKA reversal provided by the manufacturer are 25–50 IU/kg depending on the baseline international normalised ratio (INR). Nevertheless, we recommend an initial fixed dose of 1000 IU, and additional 500 IU doses evaluated on a case-by-case basis. As there is a paucity of clinical data demonstrating the efficacy and safety of this strategy, we designed this study to assess the effectiveness and safety of a four-factor (4F)-PCC for VKA reversal following a fixed-dose strategy.MethodsThis was a retrospective study of adult patients who received 4F-PCC for VKA reversal. The primary outcome was INR correction. INR correction was achieved if the first INR draw after 4F-PCC was ≤1.5. Safety outcome was any confirmed thromboembolic event within 3 months after 4F-PCC. Secondary outcomes included activated partial thromboplastin time (aPTT) correction, as well as haemostatic effectiveness for bleeding patients.ResultsA total of 145 patients were included: 106 (73.1%) in the bleeding group and 39 (26.9%) in the emergency surgery group. The INR target was reached in 102 (70.3%) patients (p<0.0001). In one case, a thromboembolic complication was possibly related to 4F-PCC. The aPTT ratio target was reached in 113 (77.9%) patients (p<0.0001), and 79 of the 106 (74.5%) patients reversed for bleeding achieved haemostatic effectiveness.ConclusionsAfter 4F-PCC, the majority of patients achieved the target INR, meaning 4F-PCC is a useful modality for rapid INR reduction. The safety profile may be considered acceptable. Fixed-dose 4F-PCC was able to restore haemostasis rapidly while minimising the risk of adverse events and optimising available resources.</description><subject>accident & emergency medicine</subject><subject>Adult</subject><subject>adverse effects</subject><subject>Anticoagulants</subject><subject>Anticoagulants - adverse effects</subject><subject>anticoagulation</subject><subject>bleeding disorders & coagulopathies</subject><subject>Blood Coagulation Factors - adverse effects</subject><subject>Clinical outcomes</subject><subject>clinical pharmacy</subject><subject>Drug administration</subject><subject>Hemorrhage</subject><subject>Humans</subject><subject>intensive & critical care</subject><subject>Original Research</subject><subject>Patients</subject><subject>Retrospective Studies</subject><subject>Statistical analysis</subject><subject>Surgery</subject><subject>therapeutic drug monitoring</subject><subject>Thromboembolism</subject><subject>Vitamin K</subject><issn>2047-9956</issn><issn>2047-9964</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2021</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><sourceid>ABUWG</sourceid><sourceid>AFKRA</sourceid><sourceid>BENPR</sourceid><sourceid>CCPQU</sourceid><recordid>eNqNkc1u1DAUhS0EolXpGyBkiQ2bUP_FjjdIqIIWUYkFsLac5GbGo8QOtmfaeQZeGg9ph58FYnVt3-8c3euD0HNKXlPK5QVs1vPaxqlihOqKEEapeIROGRGq0lqKx8dzLU_QeUquJTXnjRZcP0UnnNWaCqVP0ffPdoC8x9b3GIYBuux24CElHAZs8RC2sRpsl0PEcwx5HcPUOo-7MM0j3JXqO_A52gyFjXjnsp1K_2MxzHYVvEsZR9hBTHYsxDiGW-dXB2d3B33VhwQ4_dSv9s_Qk8GOCc7v6xn6-v7dl8vr6ubT1YfLtzdVW1OVK01Zp6VtWV_uUqm6E2Brzbgqz4wBkX2jBLFMNY2y0HKulbTQWAJdy6XmZ-jN4jtv2wn6ZYHRzNFNNu5NsM782fFubVZhZxopiOC0GLy6N4jh2xZSNpNLHYyj9RC2yTBBG8qZoqKgL_9CN-VLfVnPMKlE3VCim0KJhepiSCnCcByGEnMI3DwEbg6BmyXwInvx-yJH0UO8BbhYgHba_K8l-aU4jvpPyQ8OEsrQ</recordid><startdate>20211101</startdate><enddate>20211101</enddate><creator>Sobrino Jiménez, Carmen</creator><creator>Romero-Garrido, José Antonio</creator><creator>García-Martín, Ángeles</creator><creator>Quintana-Díaz, Manuel</creator><creator>Jiménez-Vicente, Carlos</creator><creator>González-Del Valle, Luis</creator><creator>Herrero Ambrosio, Alicia</creator><creator>Benedí-González, Juana</creator><general>British Medical Journal Publishing Group</general><general>BMJ Publishing Group LTD</general><general>BMJ Publishing Group</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>3V.</scope><scope>7X7</scope><scope>7XB</scope><scope>8FI</scope><scope>8FJ</scope><scope>8FK</scope><scope>ABUWG</scope><scope>AFKRA</scope><scope>BENPR</scope><scope>BTHHO</scope><scope>CCPQU</scope><scope>FYUFA</scope><scope>GHDGH</scope><scope>K9.</scope><scope>PQEST</scope><scope>PQQKQ</scope><scope>PQUKI</scope><scope>PRINS</scope><scope>7X8</scope><scope>5PM</scope></search><sort><creationdate>20211101</creationdate><title>Safety and effectiveness of a four-factor prothrombin complex concentrate for vitamin K antagonist reversal following a fixed-dose strategy</title><author>Sobrino Jiménez, Carmen ; Romero-Garrido, José Antonio ; García-Martín, Ángeles ; Quintana-Díaz, Manuel ; Jiménez-Vicente, Carlos ; González-Del Valle, Luis ; Herrero Ambrosio, Alicia ; Benedí-González, Juana</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-b517t-912c96ab2db516775c4ea59237c9622e06d8740a27887aeb33976ae8a0ecb3693</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2021</creationdate><topic>accident & emergency medicine</topic><topic>Adult</topic><topic>adverse effects</topic><topic>Anticoagulants</topic><topic>Anticoagulants - adverse effects</topic><topic>anticoagulation</topic><topic>bleeding disorders & coagulopathies</topic><topic>Blood Coagulation Factors - adverse effects</topic><topic>Clinical outcomes</topic><topic>clinical pharmacy</topic><topic>Drug administration</topic><topic>Hemorrhage</topic><topic>Humans</topic><topic>intensive & critical care</topic><topic>Original Research</topic><topic>Patients</topic><topic>Retrospective Studies</topic><topic>Statistical analysis</topic><topic>Surgery</topic><topic>therapeutic drug monitoring</topic><topic>Thromboembolism</topic><topic>Vitamin K</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Sobrino Jiménez, Carmen</creatorcontrib><creatorcontrib>Romero-Garrido, José Antonio</creatorcontrib><creatorcontrib>García-Martín, Ángeles</creatorcontrib><creatorcontrib>Quintana-Díaz, Manuel</creatorcontrib><creatorcontrib>Jiménez-Vicente, Carlos</creatorcontrib><creatorcontrib>González-Del Valle, Luis</creatorcontrib><creatorcontrib>Herrero Ambrosio, Alicia</creatorcontrib><creatorcontrib>Benedí-González, Juana</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>ProQuest Central (Corporate)</collection><collection>Health & Medical Collection</collection><collection>ProQuest Central (purchase pre-March 2016)</collection><collection>Hospital Premium Collection</collection><collection>Hospital Premium Collection (Alumni Edition)</collection><collection>ProQuest Central (Alumni) (purchase pre-March 2016)</collection><collection>ProQuest Central (Alumni Edition)</collection><collection>ProQuest Central UK/Ireland</collection><collection>ProQuest Central</collection><collection>BMJ Journals</collection><collection>ProQuest One Community College</collection><collection>Health Research Premium Collection</collection><collection>Health Research Premium Collection (Alumni)</collection><collection>ProQuest Health & Medical Complete (Alumni)</collection><collection>ProQuest One Academic Eastern Edition (DO NOT USE)</collection><collection>ProQuest One Academic</collection><collection>ProQuest One Academic UKI Edition</collection><collection>ProQuest Central China</collection><collection>MEDLINE - Academic</collection><collection>PubMed Central (Full Participant titles)</collection><jtitle>European journal of hospital pharmacy. Science and practice</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Sobrino Jiménez, Carmen</au><au>Romero-Garrido, José Antonio</au><au>García-Martín, Ángeles</au><au>Quintana-Díaz, Manuel</au><au>Jiménez-Vicente, Carlos</au><au>González-Del Valle, Luis</au><au>Herrero Ambrosio, Alicia</au><au>Benedí-González, Juana</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Safety and effectiveness of a four-factor prothrombin complex concentrate for vitamin K antagonist reversal following a fixed-dose strategy</atitle><jtitle>European journal of hospital pharmacy. Science and practice</jtitle><stitle>Eur J Hosp Pharm</stitle><addtitle>Eur J Hosp Pharm</addtitle><date>2021-11-01</date><risdate>2021</risdate><volume>28</volume><issue>e1</issue><spage>e66</spage><epage>e71</epage><pages>e66-e71</pages><issn>2047-9956</issn><eissn>2047-9964</eissn><abstract>ObjectivesEarly reversal of anticoagulation improves outcomes in major bleeding and emergency surgery. To reverse vitamin K antagonists (VKA), vitamin K in addition to prothrombin complex concentrate (PCC) is recommended. Dosing recommendations for VKA reversal provided by the manufacturer are 25–50 IU/kg depending on the baseline international normalised ratio (INR). Nevertheless, we recommend an initial fixed dose of 1000 IU, and additional 500 IU doses evaluated on a case-by-case basis. As there is a paucity of clinical data demonstrating the efficacy and safety of this strategy, we designed this study to assess the effectiveness and safety of a four-factor (4F)-PCC for VKA reversal following a fixed-dose strategy.MethodsThis was a retrospective study of adult patients who received 4F-PCC for VKA reversal. The primary outcome was INR correction. INR correction was achieved if the first INR draw after 4F-PCC was ≤1.5. Safety outcome was any confirmed thromboembolic event within 3 months after 4F-PCC. Secondary outcomes included activated partial thromboplastin time (aPTT) correction, as well as haemostatic effectiveness for bleeding patients.ResultsA total of 145 patients were included: 106 (73.1%) in the bleeding group and 39 (26.9%) in the emergency surgery group. The INR target was reached in 102 (70.3%) patients (p<0.0001). In one case, a thromboembolic complication was possibly related to 4F-PCC. The aPTT ratio target was reached in 113 (77.9%) patients (p<0.0001), and 79 of the 106 (74.5%) patients reversed for bleeding achieved haemostatic effectiveness.ConclusionsAfter 4F-PCC, the majority of patients achieved the target INR, meaning 4F-PCC is a useful modality for rapid INR reduction. The safety profile may be considered acceptable. Fixed-dose 4F-PCC was able to restore haemostasis rapidly while minimising the risk of adverse events and optimising available resources.</abstract><cop>England</cop><pub>British Medical Journal Publishing Group</pub><pmid>32591479</pmid><doi>10.1136/ejhpharm-2019-002114</doi><oa>free_for_read</oa></addata></record> |
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| subjects | accident & emergency medicine Adult adverse effects Anticoagulants Anticoagulants - adverse effects anticoagulation bleeding disorders & coagulopathies Blood Coagulation Factors - adverse effects Clinical outcomes clinical pharmacy Drug administration Hemorrhage Humans intensive & critical care Original Research Patients Retrospective Studies Statistical analysis Surgery therapeutic drug monitoring Thromboembolism Vitamin K |
| title | Safety and effectiveness of a four-factor prothrombin complex concentrate for vitamin K antagonist reversal following a fixed-dose strategy |
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