title: On-pump Cardiac Surgery Enhances Platelet Renewal and Impairs Aspirin Pharmacodynamics: Effects of Improved Dosing Regimens.
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)B2within the 24-hour dosing interval and urinary TXA2metabolite (TXM) excretion. Aspirin 100 mg twice-daily lowered serum TXB2and 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.
authors.affiliation: Monzino Cardiology Center, IRCCS, Milan, Italy.|University of Milan, Milan, Italy.
authors.forename: V
authors.initials: V
authors.lastname: Cavalca
authors.affiliation: Department of Pharmacology, Catholic University, Rome, Italy.
authors.forename: B
authors.initials: B
authors.lastname: Rocca
authors.affiliation: Monzino Cardiology Center, IRCCS, Milan, Italy.
authors.forename: F
authors.initials: F
authors.lastname: Veglia
authors.affiliation: Department of Pharmacology, Catholic University, Rome, Italy.
authors.forename: G
authors.initials: G
authors.lastname: Petrucci
authors.affiliation: Monzino Cardiology Center, IRCCS, Milan, Italy.
authors.forename: B
authors.initials: B
authors.lastname: Porro
authors.affiliation: Monzino Cardiology Center, IRCCS, Milan, Italy.
authors.forename: V
authors.initials: V
authors.lastname: Myasoedova
authors.affiliation: Department of Hematology, Catholic University, Rome, Italy.
authors.forename: R
authors.initials: R
authors.lastname: De Cristofaro
authors.affiliation: Monzino Cardiology Center, IRCCS, Milan, Italy.|University of Milan, Milan, Italy.
authors.forename: L
authors.initials: L
authors.lastname: Turnu
authors.affiliation: Monzino Cardiology Center, IRCCS, Milan, Italy.
authors.forename: A
authors.initials: A
authors.lastname: Bonomi
authors.affiliation: Monzino Cardiology Center, IRCCS, Milan, Italy.|University of Milan, Milan, Italy.
authors.forename: P
authors.initials: P
authors.lastname: Songia
authors.affiliation: Monzino Cardiology Center, IRCCS, Milan, Italy.
authors.forename: L
authors.initials: L
authors.lastname: Cavallotti
authors.affiliation: Monzino Cardiology Center, IRCCS, Milan, Italy.
authors.forename: M
authors.initials: M
authors.lastname: Zanobini
authors.affiliation: Monzino Cardiology Center, IRCCS, Milan, Italy.|University of Milan, Milan, Italy.
authors.forename: M
authors.initials: M
authors.lastname: Camera
authors.affiliation: Monzino Cardiology Center, IRCCS, Milan, Italy.|University of Milan, Milan, Italy.
authors.forename: F
authors.initials: F
authors.lastname: Alamanni
authors.affiliation: Policlinico San Donato Hospital, IRCCS, San Donato Milanese, Italy.
authors.forename: A
authors.initials: A
authors.lastname: Parolari
authors.affiliation: Department of Pharmacology, Catholic University, Rome, Italy.
authors.forename: C
authors.initials: C
authors.lastname: Patrono
authors.affiliation: Monzino Cardiology Center, IRCCS, Milan, Italy.
authors.forename: E
authors.initials: E
authors.lastname: Tremoli
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D001241:Aspirin / Q000008:administration & dosage*; D001792:Blood Platelets / Q000187:drug effects* / Q000378:metabolism; D001026:Coronary Artery Bypass / Q000009:adverse effects / Q000639:trends*; D003324:Coronary Artery Disease / Q000097:blood / Q000188:drug therapy* / Q000601:surgery*; D004305:Dose-Response Relationship, Drug; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D010975:Platelet Aggregation Inhibitors / Q000008:administration & dosage*; D016896:Treatment Outcome
chemical_list: D010975:Platelet Aggregation Inhibitors; D001241:Aspirin