On-pump Cardiac Surgery Enhances Platelet Renewal and Impairs Aspirin Pharmacodynamics: Effects of Improved Dosing Regimens

Clinical pharmacology and therapeutics

11 Aprile Apr 2017 4 months ago
  • Cavalca V, Veglia F, Porro B, Myasoedova V, Turnu L, Bonomi A, Songia P, Cavallotti L, Zanobini M, Camera M, Alamanni F, Tremoli E

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 100mg once-daily were studied before surgery and randomized within 36 hours post-surgery to 100mg once-daily, 100mg twice-daily or 200mg once-daily for 90 days. On day 7 post-surgery, immature and mature platelets, platelet mass, thrombopoieitin, glycocalicin, leukocytes, C-reactive protein, and interleukin-6 significantly increased. Interleukin-6 significantly correlated with immature platelets. At day 7, patients randomized to 100mg once-daily showed a significant increase in serum thromboxane (TX)B2 within the 24-hour dosing interval and urinary TXA2 metabolite (TXM) excretion. Aspirin 100mg twice-daily lowered serum TXB2 and prevented post-surgery TXM increase (p<0.01), without affecting prostacyclin metabolite excretion. Following 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.

Reference
Cavalca V, Rocca B, Veglia F, Petrucci G, Porro B, Myasoedova V, De Cristofaro R, Turnu L, Bonomi A, Songia P, Cavallotti L, Zanobini M, Camera M, Alamanni F, Parolari A, Patrono C, Tremoli E. On-pump Cardiac Surgery Enhances Platelet Renewal and Impairs Aspirin Pharmacodynamics: Effects of Improved Dosing Regimens. Clin Pharmacol Ther 2017 Apr 5. doi: 10.1002/cpt.702

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