Unfractionated heparin reverses aspirin inhibition of platelets during coronary artery bypass graft surgery.
Journal
Scientific reports
ISSN: 2045-2322
Titre abrégé: Sci Rep
Pays: England
ID NLM: 101563288
Informations de publication
Date de publication:
13 Apr 2024
13 Apr 2024
Historique:
received:
07
11
2023
accepted:
25
03
2024
medline:
13
4
2024
pubmed:
13
4
2024
entrez:
12
4
2024
Statut:
epublish
Résumé
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.
Identifiants
pubmed: 38609431
doi: 10.1038/s41598-024-58005-x
pii: 10.1038/s41598-024-58005-x
doi:
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
8572Subventions
Organisme : British Heart Foundation
ID : CH/12/1/29419
Pays : United Kingdom
Informations de copyright
© 2024. Crown.
Références
Dennis, E. A. & Norris, P. C. Eicosanoid storm in infection and inflammation. Nat. Rev. Immunol. 15, 511–523. https://doi.org/10.1038/nri3859 (2015).
doi: 10.1038/nri3859
pubmed: 26139350
pmcid: 4606863
Floyd, C. N. & Ferro, A. Mechanisms of aspirin resistance. Pharmacol. Ther. 141, 69–78. https://doi.org/10.1016/j.pharmthera.2013.08.005 (2014).
doi: 10.1016/j.pharmthera.2013.08.005
pubmed: 23993980
Hankey, G. J. & Eikelboom, J. W. Aspirin resistance. Lancet 367, 606–617. https://doi.org/10.1016/S0140-6736(06)68040-9 (2006).
doi: 10.1016/S0140-6736(06)68040-9
pubmed: 16488805
Ebrahimi, P. et al. Prevalence rate of laboratory defined aspirin resistance in cardiovascular disease patients: A systematic review and meta-analysis. Caspian J. Intern. Med. 11, 124–134. https://doi.org/10.22088/cjim.11.2.124 (2020).
doi: 10.22088/cjim.11.2.124
pubmed: 32509239
pmcid: 7265510
Wisman, P. P. et al. Platelet-reactivity tests identify patients at risk of secondary cardiovascular events: A systematic review and meta-analysis. J. Thromb. Haemost. 12, 736–747. https://doi.org/10.1111/jth.12538 (2014).
doi: 10.1111/jth.12538
pubmed: 24612413
Bednar, F. et al. Aspirin is insufficient in inhibition of platelet aggregation and thromboxane formation early after coronary artery bypass surgery. J. Thromb. Thrombolysis 27, 394–399. https://doi.org/10.1007/s11239-008-0225-y (2009).
doi: 10.1007/s11239-008-0225-y
pubmed: 18449473
Hovens, M. M. et al. Prevalence of persistent platelet reactivity despite use of aspirin: A systematic review. Am. Heart J. 153, 175–181. https://doi.org/10.1016/j.ahj.2006.10.040 (2007).
doi: 10.1016/j.ahj.2006.10.040
pubmed: 17239674
Wand, S. et al. The prevalence and clinical relevance of ASA nonresponse after cardiac surgery: A prospective bicentric study. Clin. Appl. Thromb. Hemost. 24, 179–185. https://doi.org/10.1177/1076029617693939 (2018).
doi: 10.1177/1076029617693939
pubmed: 28301911
Zimmermann, N. et al. Aspirin-induced platelet inhibition in patients undergoing cardiac surgery. Platelets 18, 528–534. https://doi.org/10.1080/09537100701321250 (2007).
doi: 10.1080/09537100701321250
pubmed: 17957569
Payne, D. A. et al. Platelet inhibition by aspirin is diminished in patients during carotid surgery: A form of transient aspirin resistance?. Thromb. Haemost. 92, 89–96. https://doi.org/10.1160/TH03-12-0758 (2004).
doi: 10.1160/TH03-12-0758
pubmed: 15213849
Webster, S. E. et al. Anti-platelet effect of aspirin is substantially reduced after administration of heparin during carotid endarterectomy. J. Vasc. Surg. 40, 463–468. https://doi.org/10.1016/j.jvs.2004.06.022 (2004).
doi: 10.1016/j.jvs.2004.06.022
pubmed: 15337874
McMahon, G. S. et al. Low molecular weight heparin significantly reduces embolisation after carotid endarterectomy—A randomised controlled trial. Eur. J. Vasc. Endovasc. Surg. 37, 633–639. https://doi.org/10.1016/j.ejvs.2009.02.009 (2009).
doi: 10.1016/j.ejvs.2009.02.009
pubmed: 19328023
Hamberg, M. & Samuelsson, B. Prostaglandin endoperoxides. Novel transformations of arachidonic acid in human platelets. Proc. Natl. Acad. Sci. USA 71, 3400–3404. https://doi.org/10.1073/pnas.71.9.3400 (1974).
doi: 10.1073/pnas.71.9.3400
pubmed: 4215079
pmcid: 433780
Mitchell, J. A. & Warner, T. D. COX isoforms in the cardiovascular system: understanding the activities of non-steroidal anti-inflammatory drugs. Nat. Rev. Drug Discov. 5, 75–86. https://doi.org/10.1038/nrd1929 (2006).
doi: 10.1038/nrd1929
pubmed: 16485347
Rauzi, F. et al. Aspirin inhibits the production of proangiogenic 15(S)-HETE by platelet cyclooxygenase-1. FASEB J. 30, 4256–4266. https://doi.org/10.1096/fj.201600530R (2016).
doi: 10.1096/fj.201600530R
pubmed: 27633788
pmcid: 5102123
Turnbull, R. E., Sander, K. N., Turnbull, J., Barrett, D. A. & Goodall, A. H. Profiling oxylipins released from human platelets activated through the GPVI collagen receptor. Prostaglandins Other Lipid Mediat. 158, 106607. https://doi.org/10.1016/j.prostaglandins.2021.106607 (2022).
doi: 10.1016/j.prostaglandins.2021.106607
pubmed: 34942378
Kulkarni, A., Nadler, J. L., Mirmira, R. G. & Casimiro, I. Regulation of tissue inflammation by 12-lipoxygenases. Biomolecules. https://doi.org/10.3390/biom11050717 (2021).
doi: 10.3390/biom11050717
pubmed: 35053156
pmcid: 8773639
Kita, Y., Shindou, H. & Shimizu, T. Cytosolic phospholipase A(2) and lysophospholipid acyltransferases. Biochim. Biophys. Acta Mol. Cell Biol. Lipids 838–845, 2019. https://doi.org/10.1016/j.bbalip.2018.08.006 (1864).
doi: 10.1016/j.bbalip.2018.08.006
Chesney, C. M., Pifer, D. D., Byers, L. W. & Muirhead, E. E. Effect of platelet-activating factor (PAF) on human platelets. Blood 59, 582–585 (1982).
doi: 10.1182/blood.V59.3.582.582
pubmed: 7037068
McMahon, G. S., Jones, C. I., Hayes, P. D., Naylor, A. R. & Goodall, A. H. Transient heparin-induced platelet activation linked to generation of platelet 12-lipoxygenase. Findings from a randomised controlled trial. Thromb. Haemost. 109, 1099–1107. https://doi.org/10.1160/TH12-11-0793 (2013).
doi: 10.1160/TH12-11-0793
pubmed: 23494053
Dachary-Prigent, J., Freyssinet, J. M., Pasquet, J. M., Carron, J. C. & Nurden, A. T. Annexin V as a probe of aminophospholipid exposure and platelet membrane vesiculation: A flow cytometry study showing a role for free sulfhydryl groups. Blood 81, 2554–2565 (1993).
doi: 10.1182/blood.V81.10.2554.2554
pubmed: 8490169
Myrup, B., Yokoyama, H., Kristiansen, O. P., Ostergaard, P. B. & Olivecrona, T. Release of endothelium-associated proteins into blood by injection of heparin in normal subjects and in patients with Type 1 diabetes. Diabet. Med. 21, 1135–1140. https://doi.org/10.1111/j.1464-5491.2004.01313.x (2004).
doi: 10.1111/j.1464-5491.2004.01313.x
pubmed: 15384962
Tloti, M. A., Moon, D. G., Weston, L. K. & Kaplan, J. E. Effect of 13-hydroxyoctadeca-9,11-dienoic acid (13-HODE) on thrombin induced platelet adherence to endothelial cells in vitro. Thromb. Res. 62, 305–317. https://doi.org/10.1016/0049-3848(91)90151-l (1991).
doi: 10.1016/0049-3848(91)90151-l
pubmed: 1866713
Truitt, A., McNeill, G. & Vanderhoek, J. Y. Antiplatelet effects of conjugated linoleic acid isomers. Biochim. Biophys. Acta 1438, 239–246. https://doi.org/10.1016/s1388-1981(99)00055-4 (1999).
doi: 10.1016/s1388-1981(99)00055-4
pubmed: 10320806
Greinacher, A., Selleng, K. & Warkentin, T. E. Autoimmune heparin-induced thrombocytopenia. J. Thromb. Haemost. 15, 2099–2114. https://doi.org/10.1111/jth.13813 (2017).
doi: 10.1111/jth.13813
pubmed: 28846826
Goodfriend, T. L. et al. Heparin, lipoproteins, and oxygenated fatty acids in blood: A cautionary note. Prostaglandins Leukot. Essent. Fatty Acids 77, 363–366. https://doi.org/10.1016/j.plefa.2007.10.012 (2007).
doi: 10.1016/j.plefa.2007.10.012
pubmed: 18036802
pmcid: 2705328
Persson, E. Lipoprotein lipase, hepatic lipase and plasma lipolytic activity. Effects of heparin and a low molecular weight heparin fragment (Fragmin). Acta Med. Scand. Suppl. 724, 1–56 (1988).
pubmed: 2843005
Tornvall, P., Olivecrona, G., Karpe, F., Hamsten, A. & Olivecrona, T. Lipoprotein lipase mass and activity in plasma and their increase after heparin are separate parameters with different relations to plasma lipoproteins. Arterioscler. Thromb. Vasc. Biol. 15, 1086–1093. https://doi.org/10.1161/01.atv.15.8.1086 (1995).
doi: 10.1161/01.atv.15.8.1086
pubmed: 7627700
Gao, C. et al. Heparin promotes platelet responsiveness by potentiating alphaIIbbeta3-mediated outside-in signaling. Blood 117, 4946–4952. https://doi.org/10.1182/blood-2010-09-307751 (2011).
doi: 10.1182/blood-2010-09-307751
pubmed: 21368290
pmcid: 3100701
Yagi, M. et al. Heparin modulates the conformation and signaling of platelet integrin alphaIIbbeta3. Thromb. Res. 129, 743–749. https://doi.org/10.1016/j.thromres.2011.11.054 (2012).
doi: 10.1016/j.thromres.2011.11.054
pubmed: 22197178
Wang, B. et al. Metabolism pathways of arachidonic acids: Mechanisms and potential therapeutic targets. Signal Transduct. Target Ther. 6, 94. https://doi.org/10.1038/s41392-020-00443-w (2021).
doi: 10.1038/s41392-020-00443-w
pubmed: 33637672
pmcid: 7910446
Payne, D. A., Jones, C. I., Hayes, P. D., Naylor, A. R. & Goodall, A. H. Therapeutic benefit of low-dose clopidogrel in patients undergoing carotid surgery is linked to variability in the platelet adenosine diphosphate response and patients’ weight. Stroke 38, 2464–2469. https://doi.org/10.1161/STROKEAHA.107.486787 (2007).
doi: 10.1161/STROKEAHA.107.486787
pubmed: 17656657
Janes, S. L., Wilson, D. J., Chronos, N. & Goodall, A. H. Evaluation of whole blood flow cytometric detection of platelet bound fibrinogen on normal subjects and patients with activated platelets. Thromb. Haemost. 70, 659–666 (1993).
doi: 10.1055/s-0038-1649645
pubmed: 8115992
Thomas, C. P. et al. Phospholipid-esterified eicosanoids are generated in agonist-activated human platelets and enhance tissue factor-dependent thrombin generation. J. Biol. Chem. 285, 6891–6903. https://doi.org/10.1074/jbc.M109.078428 (2010).
doi: 10.1074/jbc.M109.078428
pubmed: 20061396
pmcid: 2844139