Unfractionated heparin reverses aspirin inhibition of platelets during coronary artery bypass graft surgery
Abstract Unfractionated heparin (UFH) is an effective antithrombotic during surgery but has known adverse effects, in particular on platelets. A marked increase in platelet responsiveness has previously been observed in patients within minutes of receiving UFH, despite adequate inhibition by aspirin...
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| Format: | Article |
| Language: | English |
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Nature Portfolio
2024-04-01
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| Series: | Scientific Reports |
| Online Access: | https://doi.org/10.1038/s41598-024-58005-x |
| _version_ | 1797209334126477312 |
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| author | Robert E. Turnbull Azhar Hafeez Katrin N. Sander David A. Barrett Gavin J. Murphy Alison H. Goodall |
| author_facet | Robert E. Turnbull Azhar Hafeez Katrin N. Sander David A. Barrett Gavin J. Murphy Alison H. Goodall |
| author_sort | Robert E. Turnbull |
| collection | DOAJ |
| description | Abstract Unfractionated heparin (UFH) is an effective antithrombotic during surgery but has known adverse effects, in particular on platelets. A marked increase in platelet responsiveness has previously been observed in patients within minutes of receiving UFH, despite adequate inhibition by aspirin prior to heparin. We studied this phenomenon in patients undergoing cardiac artery bypass grafting (n = 17) to determine whether the effects of heparin were systemic or platelet-specific. All patients’ platelets were fully inhibited by aspirin prior to surgery, but within 3 min of receiving heparin spontaneous aggregation and responses to arachidonic acid (AA) and ADP increased significantly (p ≥ 0.0002), and activated platelets were found in the circulation. While there was no rise in thromboxane in the plasma following heparin, levels of the major platelet 12-lipoxygenase product, 12-HETE, rose significantly. Mixing experiments demonstrated that the changes caused by heparin resided primarily in the platelets, while addition of AA pathway inhibitors, and analysis of oxylipins provided evidence that, following heparin, aggregating platelets regained their ability to synthesise thromboxane. These findings highlight potentially unrecognised pro-thrombotic and pro-inflammatory changes during CABG surgery, and provide further evidence of adverse effects associated with UFH. |
| first_indexed | 2024-04-24T09:53:03Z |
| format | Article |
| id | doaj.art-3675cf54856d4cb8b2e9d6cca4be341b |
| institution | Directory Open Access Journal |
| issn | 2045-2322 |
| language | English |
| last_indexed | 2024-04-24T09:53:03Z |
| publishDate | 2024-04-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | Scientific Reports |
| spelling | doaj.art-3675cf54856d4cb8b2e9d6cca4be341b2024-04-14T11:15:54ZengNature PortfolioScientific Reports2045-23222024-04-0114111110.1038/s41598-024-58005-xUnfractionated heparin reverses aspirin inhibition of platelets during coronary artery bypass graft surgeryRobert E. Turnbull0Azhar Hafeez1Katrin N. Sander2David A. Barrett3Gavin J. Murphy4Alison H. Goodall5Department of Cardiovascular Sciences, University of Leicester and NIHR Cardiovascular Biomedical Research Centre, Glenfield HospitalDepartment of Cardiovascular Sciences, University of Leicester and NIHR Cardiovascular Biomedical Research Centre, Glenfield HospitalCentre for Analytical Bioscience, Advanced Materials and Healthcare Division, School of Pharmacy, University of NottinghamCentre for Analytical Bioscience, Advanced Materials and Healthcare Division, School of Pharmacy, University of NottinghamDepartment of Cardiovascular Sciences, University of Leicester and NIHR Cardiovascular Biomedical Research Centre, Glenfield HospitalDepartment of Cardiovascular Sciences, University of Leicester and NIHR Cardiovascular Biomedical Research Centre, Glenfield HospitalAbstract Unfractionated heparin (UFH) is an effective antithrombotic during surgery but has known adverse effects, in particular on platelets. A marked increase in platelet responsiveness has previously been observed in patients within minutes of receiving UFH, despite adequate inhibition by aspirin prior to heparin. We studied this phenomenon in patients undergoing cardiac artery bypass grafting (n = 17) to determine whether the effects of heparin were systemic or platelet-specific. All patients’ platelets were fully inhibited by aspirin prior to surgery, but within 3 min of receiving heparin spontaneous aggregation and responses to arachidonic acid (AA) and ADP increased significantly (p ≥ 0.0002), and activated platelets were found in the circulation. While there was no rise in thromboxane in the plasma following heparin, levels of the major platelet 12-lipoxygenase product, 12-HETE, rose significantly. Mixing experiments demonstrated that the changes caused by heparin resided primarily in the platelets, while addition of AA pathway inhibitors, and analysis of oxylipins provided evidence that, following heparin, aggregating platelets regained their ability to synthesise thromboxane. These findings highlight potentially unrecognised pro-thrombotic and pro-inflammatory changes during CABG surgery, and provide further evidence of adverse effects associated with UFH.https://doi.org/10.1038/s41598-024-58005-x |
| spellingShingle | Robert E. Turnbull Azhar Hafeez Katrin N. Sander David A. Barrett Gavin J. Murphy Alison H. Goodall Unfractionated heparin reverses aspirin inhibition of platelets during coronary artery bypass graft surgery Scientific Reports |
| title | Unfractionated heparin reverses aspirin inhibition of platelets during coronary artery bypass graft surgery |
| title_full | Unfractionated heparin reverses aspirin inhibition of platelets during coronary artery bypass graft surgery |
| title_fullStr | Unfractionated heparin reverses aspirin inhibition of platelets during coronary artery bypass graft surgery |
| title_full_unstemmed | Unfractionated heparin reverses aspirin inhibition of platelets during coronary artery bypass graft surgery |
| title_short | Unfractionated heparin reverses aspirin inhibition of platelets during coronary artery bypass graft surgery |
| title_sort | unfractionated heparin reverses aspirin inhibition of platelets during coronary artery bypass graft surgery |
| url | https://doi.org/10.1038/s41598-024-58005-x |
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