Key result
Female sex is linked to significantly higher ADP-dependent platelet reactivity vs males across antiplatelet regimens.
Why the study?
Emerging evidence suggests sex-specific differences in platelet biology and clinical responses to antiplatelet agents, but large standardized data on platelet reactivity by sex are lacking.
Does female sex compared to male sex affect platelet reactivity in the presence or absence of antiplatelet therapy?
Observational (n=5,687)
Does female sex compared to male sex affect platelet reactivity in the presence or absence of antiplatelet therapy?
Females demonstrate heightened baseline ADP-dependent platelet reactivity and diminished response to aspirin and clopidogrel monotherapy compared to males, suggesting a potential need for sex-specific antiplatelet strategies.
May support sex-specific antiplatelet considerations; leaves open confirmation in prospective outcome trials.
AIMS: Emerging evidence suggests sex-specific differences in platelet biology and clinical responses to antiplatelet agents. Light transmission aggregometry (LTA) represents the historical gold standard for the assessment of platelet reactivity but is influenced by pre-analytical and analytical variables. We analysed a large dataset of patients undergoing LTA using a standardized methodology to investigate the impact of sex on platelet reactivity with or without antiplatelet therapy. METHODS AND RESULTS: Between 2004 and 2022, 11,913 patients sequentially underwent LTA assessments following stimulation with adenosine diphosphate (ADP) (2 µM), collagen (2 µg/mL), arachidonic acid (AA, 0.5 mM), and epinephrine (10 µM). After applying study entry criteria, 5687 patients were included: 428 healthy volunteers (HV, F = 273; M = 155), 1055 controls (CTR; F = 725; M = 330), 3289 aspirin-treated patients (ASA; F = 2058; M = 1231), 430 clopidogrel-treated patients (CLOP; F = 272; M = 158), and 485 patients on dual antiplatelet therapy (DAPT; F = 166; M = 319). Within each group, results were analysed and compared between males and females.Females exhibited significantly greater platelet reactivity in response to ADP compared to males in the HV (P = 0.004), CTR (P < 0.0001), ASA (P < 0.0001), and CLOP (P < 0.018) groups, but not in the DAPT group. Among aspirin-treated patients, females showed increased platelet reactivity (P < 0.0001) in response to collagen, compared with males. CONCLUSION: Females exhibit heightened baseline ADP-dependent platelet reactivity and a diminished response to aspirin and clopidogrel monotherapy compared to males.
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Galli et al. (2025) conducted an observational in Patients undergoing light transmission aggregometry (n=5,687). Female sex vs. Male sex was evaluated on Platelet reactivity in response to ADP (p=<0.0001). Female sex was associated with significantly greater ADP-dependent platelet reactivity compared to males in healthy volunteers, controls, and patients on aspirin or clopidogrel monotherapy.
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