On‐pump Cardiac Surgery Enhances Platelet Renewal and Impairs Aspirin Pharmacodynamics: Effects of Improved Dosing Regimens
On‐pump cardiac surgery may trigger inflammation and accelerate platelet cyclooxygenase‐1 renewal, thereby modifying low‐dose aspirin pharmacodynamics. Thirty‐seven patients on standard aspirin 100 mg once‐daily were studied before surgery and randomized within 36 hours postsurgery to 100 mg once‐da...
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| Veröffentlicht in: | Clinical pharmacology and therapeutics 2017-11, Vol.102 (5), p.849-858 |
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| creator | Cavalca, V Rocca, B Veglia, F Petrucci, G Porro, B Myasoedova, V Cristofaro, R Turnu, L Bonomi, A Songia, P Cavallotti, L Zanobini, M Camera, M Alamanni, F Parolari, A Patrono, C Tremoli, E |
| description | On‐pump cardiac surgery may trigger inflammation and accelerate platelet cyclooxygenase‐1 renewal, thereby modifying low‐dose aspirin pharmacodynamics. Thirty‐seven patients on standard aspirin 100 mg once‐daily were studied before surgery and randomized within 36 hours postsurgery to 100 mg once‐daily, 100 mg twice‐daily, or 200 mg once‐daily for 90 days. On day 7 postsurgery, immature and mature platelets, platelet mass, thrombopoietin, glycocalicin, leukocytes, C‐reactive protein, and interleukin‐6 significantly increased. Interleukin‐6 significantly correlated with immature platelets. At day 7, patients randomized to 100 mg once‐daily showed a significant increase in serum thromboxane (TX)B2 within the 24‐hour dosing interval and urinary TXA2 metabolite (TXM) excretion. Aspirin 100 mg twice‐daily lowered serum TXB2 and prevented postsurgery TXM increase (P < 0.01), without affecting prostacyclin metabolite excretion. After cardiac surgery, shortening the dosing interval, but not doubling the once‐daily dose, rescues the impaired antiplatelet effect of low‐dose aspirin and prevents platelet activation associated with acute inflammation and enhanced platelet turnover. |
| doi_str_mv | 10.1002/cpt.702 |
| format | Article |
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Thirty‐seven patients on standard aspirin 100 mg once‐daily were studied before surgery and randomized within 36 hours postsurgery to 100 mg once‐daily, 100 mg twice‐daily, or 200 mg once‐daily for 90 days. On day 7 postsurgery, immature and mature platelets, platelet mass, thrombopoietin, glycocalicin, leukocytes, C‐reactive protein, and interleukin‐6 significantly increased. Interleukin‐6 significantly correlated with immature platelets. At day 7, patients randomized to 100 mg once‐daily showed a significant increase in serum thromboxane (TX)B2 within the 24‐hour dosing interval and urinary TXA2 metabolite (TXM) excretion. Aspirin 100 mg twice‐daily lowered serum TXB2 and prevented postsurgery TXM increase (P < 0.01), without affecting prostacyclin metabolite excretion. After cardiac surgery, shortening the dosing interval, but not doubling the once‐daily dose, rescues the impaired antiplatelet effect of low‐dose aspirin and prevents platelet activation associated with acute inflammation and enhanced platelet turnover.</description><identifier>ISSN: 0009-9236</identifier><identifier>EISSN: 1532-6535</identifier><identifier>DOI: 10.1002/cpt.702</identifier><identifier>PMID: 28379623</identifier><language>eng</language><publisher>United States</publisher><subject>Aged ; Aged, 80 and over ; Aspirin - administration & dosage ; Blood Platelets - drug effects ; Blood Platelets - metabolism ; Coronary Artery Bypass - adverse effects ; Coronary Artery Bypass - trends ; Coronary Artery Disease - blood ; Coronary Artery Disease - drug therapy ; Coronary Artery Disease - surgery ; Dose-Response Relationship, Drug ; Female ; Humans ; Male ; Middle Aged ; Platelet Aggregation Inhibitors - administration & dosage ; Treatment Outcome</subject><ispartof>Clinical pharmacology and therapeutics, 2017-11, Vol.102 (5), p.849-858</ispartof><rights>2017 American Society for Clinical Pharmacology and Therapeutics</rights><rights>2017 American Society for Clinical Pharmacology and Therapeutics.</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c4162-360da43e051f5857202846003a7ffa3d7deffb3e1fd9908bf2b93b16a8982b833</citedby><cites>FETCH-LOGICAL-c4162-360da43e051f5857202846003a7ffa3d7deffb3e1fd9908bf2b93b16a8982b833</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://onlinelibrary.wiley.com/doi/pdf/10.1002%2Fcpt.702$$EPDF$$P50$$Gwiley$$H</linktopdf><linktohtml>$$Uhttps://onlinelibrary.wiley.com/doi/full/10.1002%2Fcpt.702$$EHTML$$P50$$Gwiley$$H</linktohtml><link.rule.ids>314,776,780,1411,27901,27902,45550,45551</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/28379623$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Cavalca, V</creatorcontrib><creatorcontrib>Rocca, B</creatorcontrib><creatorcontrib>Veglia, F</creatorcontrib><creatorcontrib>Petrucci, G</creatorcontrib><creatorcontrib>Porro, B</creatorcontrib><creatorcontrib>Myasoedova, V</creatorcontrib><creatorcontrib>Cristofaro, R</creatorcontrib><creatorcontrib>Turnu, L</creatorcontrib><creatorcontrib>Bonomi, A</creatorcontrib><creatorcontrib>Songia, P</creatorcontrib><creatorcontrib>Cavallotti, L</creatorcontrib><creatorcontrib>Zanobini, M</creatorcontrib><creatorcontrib>Camera, M</creatorcontrib><creatorcontrib>Alamanni, F</creatorcontrib><creatorcontrib>Parolari, A</creatorcontrib><creatorcontrib>Patrono, C</creatorcontrib><creatorcontrib>Tremoli, E</creatorcontrib><title>On‐pump Cardiac Surgery Enhances Platelet Renewal and Impairs Aspirin Pharmacodynamics: Effects of Improved Dosing Regimens</title><title>Clinical pharmacology and therapeutics</title><addtitle>Clin Pharmacol Ther</addtitle><description>On‐pump cardiac surgery may trigger inflammation and accelerate platelet cyclooxygenase‐1 renewal, thereby modifying low‐dose aspirin pharmacodynamics. Thirty‐seven patients on standard aspirin 100 mg once‐daily were studied before surgery and randomized within 36 hours postsurgery to 100 mg once‐daily, 100 mg twice‐daily, or 200 mg once‐daily for 90 days. On day 7 postsurgery, immature and mature platelets, platelet mass, thrombopoietin, glycocalicin, leukocytes, C‐reactive protein, and interleukin‐6 significantly increased. Interleukin‐6 significantly correlated with immature platelets. At day 7, patients randomized to 100 mg once‐daily showed a significant increase in serum thromboxane (TX)B2 within the 24‐hour dosing interval and urinary TXA2 metabolite (TXM) excretion. Aspirin 100 mg twice‐daily lowered serum TXB2 and prevented postsurgery TXM increase (P < 0.01), without affecting prostacyclin metabolite excretion. After cardiac surgery, shortening the dosing interval, but not doubling the once‐daily dose, rescues the impaired antiplatelet effect of low‐dose aspirin and prevents platelet activation associated with acute inflammation and enhanced platelet turnover.</description><subject>Aged</subject><subject>Aged, 80 and over</subject><subject>Aspirin - administration & dosage</subject><subject>Blood Platelets - drug effects</subject><subject>Blood Platelets - metabolism</subject><subject>Coronary Artery Bypass - adverse effects</subject><subject>Coronary Artery Bypass - trends</subject><subject>Coronary Artery Disease - blood</subject><subject>Coronary Artery Disease - drug therapy</subject><subject>Coronary Artery Disease - surgery</subject><subject>Dose-Response Relationship, Drug</subject><subject>Female</subject><subject>Humans</subject><subject>Male</subject><subject>Middle Aged</subject><subject>Platelet Aggregation Inhibitors - administration & dosage</subject><subject>Treatment Outcome</subject><issn>0009-9236</issn><issn>1532-6535</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2017</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNp1kE1LwzAAhoMobn7gP5DcPEhnPvqReBt16mCwofNc0ibZIm1aks7Rg-BP8Df6S-yYevP08sLDc3gAuMBohBEiN0XTjhJEDsAQR5QEcUSjQzBECPGAExoPwIn3r_0NOWPHYEAYTXhM6BC8z-3Xx2ezqRqYCieNKODzxq2U6-DEroUtlIeLUrSqVC18UlZtRQmFlXBaNcI4D8e-Mc5YuFgLV4milp0VlSn8LZxorYrWw1rvYFe_KQnvam_sqhetTKWsPwNHWpRenf_sKXi5nyzTx2A2f5im41lQhDgmAY2RFCFVKMI6YlFCEGFhjBAVidaCykQqrXOqsJacI5ZrknOa41gwzkjOKD0FV3tv4WrvndJZ40wlXJdhlO0CZn3ArA_Yk5d7stnklZJ_3G-xHrjeA1tTqu4_T5YuljvdN9wPe7A</recordid><startdate>201711</startdate><enddate>201711</enddate><creator>Cavalca, V</creator><creator>Rocca, B</creator><creator>Veglia, F</creator><creator>Petrucci, G</creator><creator>Porro, B</creator><creator>Myasoedova, V</creator><creator>Cristofaro, R</creator><creator>Turnu, L</creator><creator>Bonomi, A</creator><creator>Songia, P</creator><creator>Cavallotti, L</creator><creator>Zanobini, M</creator><creator>Camera, M</creator><creator>Alamanni, F</creator><creator>Parolari, A</creator><creator>Patrono, C</creator><creator>Tremoli, E</creator><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope></search><sort><creationdate>201711</creationdate><title>On‐pump Cardiac Surgery Enhances Platelet Renewal and Impairs Aspirin Pharmacodynamics: Effects of Improved Dosing Regimens</title><author>Cavalca, V ; Rocca, B ; Veglia, F ; Petrucci, G ; Porro, B ; Myasoedova, V ; Cristofaro, R ; Turnu, L ; Bonomi, A ; Songia, P ; Cavallotti, L ; Zanobini, M ; Camera, M ; Alamanni, F ; Parolari, A ; Patrono, C ; Tremoli, E</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c4162-360da43e051f5857202846003a7ffa3d7deffb3e1fd9908bf2b93b16a8982b833</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2017</creationdate><topic>Aged</topic><topic>Aged, 80 and over</topic><topic>Aspirin - administration & dosage</topic><topic>Blood Platelets - drug effects</topic><topic>Blood Platelets - metabolism</topic><topic>Coronary Artery Bypass - adverse effects</topic><topic>Coronary Artery Bypass - trends</topic><topic>Coronary Artery Disease - blood</topic><topic>Coronary Artery Disease - drug therapy</topic><topic>Coronary Artery Disease - surgery</topic><topic>Dose-Response Relationship, Drug</topic><topic>Female</topic><topic>Humans</topic><topic>Male</topic><topic>Middle Aged</topic><topic>Platelet Aggregation Inhibitors - administration & dosage</topic><topic>Treatment Outcome</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Cavalca, V</creatorcontrib><creatorcontrib>Rocca, B</creatorcontrib><creatorcontrib>Veglia, F</creatorcontrib><creatorcontrib>Petrucci, G</creatorcontrib><creatorcontrib>Porro, B</creatorcontrib><creatorcontrib>Myasoedova, V</creatorcontrib><creatorcontrib>Cristofaro, R</creatorcontrib><creatorcontrib>Turnu, L</creatorcontrib><creatorcontrib>Bonomi, A</creatorcontrib><creatorcontrib>Songia, P</creatorcontrib><creatorcontrib>Cavallotti, L</creatorcontrib><creatorcontrib>Zanobini, M</creatorcontrib><creatorcontrib>Camera, M</creatorcontrib><creatorcontrib>Alamanni, F</creatorcontrib><creatorcontrib>Parolari, A</creatorcontrib><creatorcontrib>Patrono, C</creatorcontrib><creatorcontrib>Tremoli, E</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><jtitle>Clinical pharmacology and therapeutics</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Cavalca, V</au><au>Rocca, B</au><au>Veglia, F</au><au>Petrucci, G</au><au>Porro, B</au><au>Myasoedova, V</au><au>Cristofaro, R</au><au>Turnu, L</au><au>Bonomi, A</au><au>Songia, P</au><au>Cavallotti, L</au><au>Zanobini, M</au><au>Camera, M</au><au>Alamanni, F</au><au>Parolari, A</au><au>Patrono, C</au><au>Tremoli, E</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>On‐pump Cardiac Surgery Enhances Platelet Renewal and Impairs Aspirin Pharmacodynamics: Effects of Improved Dosing Regimens</atitle><jtitle>Clinical pharmacology and therapeutics</jtitle><addtitle>Clin Pharmacol Ther</addtitle><date>2017-11</date><risdate>2017</risdate><volume>102</volume><issue>5</issue><spage>849</spage><epage>858</epage><pages>849-858</pages><issn>0009-9236</issn><eissn>1532-6535</eissn><abstract>On‐pump cardiac surgery may trigger inflammation and accelerate platelet cyclooxygenase‐1 renewal, thereby modifying low‐dose aspirin pharmacodynamics. Thirty‐seven patients on standard aspirin 100 mg once‐daily were studied before surgery and randomized within 36 hours postsurgery to 100 mg once‐daily, 100 mg twice‐daily, or 200 mg once‐daily for 90 days. On day 7 postsurgery, immature and mature platelets, platelet mass, thrombopoietin, glycocalicin, leukocytes, C‐reactive protein, and interleukin‐6 significantly increased. Interleukin‐6 significantly correlated with immature platelets. At day 7, patients randomized to 100 mg once‐daily showed a significant increase in serum thromboxane (TX)B2 within the 24‐hour dosing interval and urinary TXA2 metabolite (TXM) excretion. Aspirin 100 mg twice‐daily lowered serum TXB2 and prevented postsurgery TXM increase (P < 0.01), without affecting prostacyclin metabolite excretion. After cardiac surgery, shortening the dosing interval, but not doubling the once‐daily dose, rescues the impaired antiplatelet effect of low‐dose aspirin and prevents platelet activation associated with acute inflammation and enhanced platelet turnover.</abstract><cop>United States</cop><pmid>28379623</pmid><doi>10.1002/cpt.702</doi><tpages>10</tpages><oa>free_for_read</oa></addata></record> |
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| ispartof | Clinical pharmacology and therapeutics, 2017-11, Vol.102 (5), p.849-858 |
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| source | MEDLINE; Wiley Online Library Journals Frontfile Complete |
| subjects | Aged Aged, 80 and over Aspirin - administration & dosage Blood Platelets - drug effects Blood Platelets - metabolism Coronary Artery Bypass - adverse effects Coronary Artery Bypass - trends Coronary Artery Disease - blood Coronary Artery Disease - drug therapy Coronary Artery Disease - surgery Dose-Response Relationship, Drug Female Humans Male Middle Aged Platelet Aggregation Inhibitors - administration & dosage Treatment Outcome |
| title | On‐pump Cardiac Surgery Enhances Platelet Renewal and Impairs Aspirin Pharmacodynamics: Effects of Improved Dosing Regimens |
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