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The Impact of Sex on Platelet Reponses to Aspirin in Patients with Peripheral Artery Disease
*Sasha Suarez Ferreira1, *Ryan Hall1, *Katherine Morrow1, *Shiv Patel1, *Ivy Lee1, *Fanah Hagos1, *Nikolaos Zacharias1, *Kellie Machlus2, Matthew Eagleton1, *Anahita Dua1
1Massachusetts General Hospital, Boston, MA; 2Boston Children's Hospital, Boston, MA

Objective: Women with peripheral artery disease have poorer limb salvage outcomes in spite of having lower risk factors for vascular disease than their male counterparts. Mono antiplatelet therapy with aspirin is the cornerstone of medical treatment of PAD to reduce the risk of arterial thrombosis but platelets in women may have a variable response to this standard of care compared to males. Viscoelastic assays, such as Thromboelastography with platelet mapping (TEG-PM), have been utilized to identify prothrombotic states and may provide insight into a patient's real-time coagulation profile and their response to specific antiplatelet medications. The aim of this prospective, observational study was to delineate the sex differences in platelet function using TEG-PM in patients with PAD on aspirin post revascularization for PAD. Methods: All patients with PAD undergoing revascularization on aspirin monotherapy were prospectively enrolled between December 2020 and September 2023. The cohort was divided by sex; demographics, medications, procedure type, and outcomes namely thrombosis were documented. Serial perioperative TEG-PM assays (1, 3 and 6 months) were performed up to six months postoperatively and the platelet function was evaluated in both groups. Statistical analysis between women and men was performed using unpaired t-test to identify sex differences in platelet function. Contingency tables were used to analyze categorical characteristics. Results: Over the study period, a total of 303 patients were enrolled. Of this cohort 149 patients met study criteria and 266 samples were analyzed. 52(34.89%) patients were women and 97(65.11%) were men. In the platelet mapping assay, women showed significantly greater MAActF and MAAA, than men [16.66 vs. 14.94, p<0.03 and 37.26 vs. 32.38, p<0.01] respectively indicating stronger thrombotic propensity (Graph 1 and Graph 2). Additionally, platelet function in terms of platelet inhibition was significantly lower in women compared to men [52.95% vs. 61.65%, p<0.05] on the same medication (Graph 3). In clinical outcomes reported as thrombotic events, women showed significantly higher occlusion in the area of intervention than men [4 vs. 1, p<0.05] on the same medication (Table 1). Conclusions: There is a growing awareness of the variations in the natural course, underlying mechanisms, and resulting outcomes of cardiovascular conditions, including PAD, in relation to sex. In this study, women did not achieve the same levels of platelet inhibition compared on men even though they were on the same medication. Women displayed a procoagulant tendency in comparison to men when administered aspirin. Overall, aspirin monotherapy may be potentially sufficient for men, but women may require increased doses and/or additional antiplatelet medications to achieve therapeutic effect.






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