Gender-based differences in platelet function and platelet reactivity to P2Y12 inhibitors

• Published in: PloS one 2019-11, Vol.14 (11), p.e0225771-e0225771
• Main Authors: Ranucci, Marco, Aloisio, Tommaso, Di Dedda, Umberto, Menicanti, Lorenzo, de Vincentiis, Carlo, Baryshnikova, Ekaterina
• Format: Article
• Language: English
• Subjects: Adenosine diphosphate; Adenosine Diphosphate - metabolism; Aged; Biology and Life Sciences; Blood platelets; Blood Platelets - drug effects; Blood Platelets - physiology; Cardiac Surgical Procedures; Cardiovascular disease; Clinical outcomes; Clopidogrel; Confidence intervals; Data collection; Ethics; Female; Gender; Heart surgery; Humans; Inhibitors; Intensive care; Laboratories; Male; Males; Medicine and Health Sciences; Men; Middle Aged; Obesity; Patients; Platelet Aggregation - drug effects; Platelet Count; Platelet Function Tests; Platelets; Purinergic P2Y Receptor Antagonists - pharmacology; Reactivity; Residual effects; Sex Factors; Studies; Surgery; Systematic review; Test procedures
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0225771

Gender influences platelet biology. Women have a larger platelet count, but gender-based differences in platelet function remain debated. We performed a study addressing gender-based differences in platelet function using point-of-care platelet function tests (PFT). The patient population consisted of 760 cardiac surgery patients where preoperative PFT (multiple-electrode aggregometry [MEA]) were available. Platelet count and function at the ADPtest and TRAPtest were compared in the overall population and separately in patients with or without residual effects of P2Y12 inhibitors. Women had a significantly (P = 0.001) higher platelet count but a non-significantly higher platelet reactivity to ADP. In clopidogrel-treated patients, the platelets ADP reactivity was significantly (P = 0.031) higher in women, and platelet count was the main determinant of platelet hyper-reactivity. Within patients under full clopidogrel effects, women with a platelet count ≥ 200,000 cells/μL had a significantly (P = 0.023) higher rate of high-on-treatment platelet reactivity (HTPR, 45.5%) with respect to males with a platelet count < 200,000 cells/μL (11.9%), with a relative risk of 6.2 (95% confidence interval 1.4-29). Our findings confirm that women have a larger platelet count than men, and that this is associated to a trend towards a higher platelet reactivity. HTPR is largely represented in women with a high platelet count. This generates the hypothesis that women requiring P2Y12 inhibitors could potentially benefit from larger doses of drug or should be treated with anti-platelet agents with a low rate of HTPR.