Influence of Sex on Platelet Reactivity in Response to Aspirin

Figures

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  Figure 1. Experimental protocol, sample testing, and comparisons. Patients in 4 experimental cohorts were exposed to aspirin (ASA) and samples were taken at baseline, 3 hours after ASA exposure, and after 2 or 4 weeks of daily ASA therapy. Platelet‐rich plasma (PRP) samples were collected and multiple tests of platelet function were performed as shown. Men and women were compared using statistical models to determine the main effect of ASA treatment and the interaction effect of sex on ASA. Additional comparisons between experimental time points and for other platelet function data were made as shown. AA indicates arachidonic acid; CAD, coronary artery disease, COL, collagen; COX‐1, cyclooxygenase‐1; DM, diabetes mellitus; EPI, epinephrine; HV, healthy volunteer; M/W, men/women; PFA, platelet function analyzer; PGE2, prostaglandin E2; pK/pD, pharmacokinetic/pharmacodynamic; and TXB2, thromboxane B2.

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  Figure 2. Sex differences in platelet aggregation both at baseline and after treatment with aspirin (ASA). Values for epinephrine (EPI), ADP, and collagen (COL) are expressed as standardized mean area under the curve of light transmittance aggregometry with standard error bars. Agonist concentrations are denoted above each frame and are expressed in μmol/L for EPI and ADP and as mg/mL for COL. Significant differences (P<0.05) are noted by an asterisk. The data used to generate this figure are reported in Table S1. M indicates men; PFA, platelet function analyzer; and W, women.

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  Figure 3. Treatment effect of aspirin stratified by sex, standardized in comparison to baseline platelet aggregation for each agonist, which is set at 0. Significant sex differences are seen for the change in platelet aggregation in response to platelet agonists epinephrine (EPI) (at 0.5 and 1 μmol/L) and collagen (COL) (at 2 and 5 mg/mL) after treatment with aspirin. Agonist concentrations are denoted on the left and are expressed in μmol/L for EPI and ADP and as mg/mL for COL. Standard error bars are displayed, and significant differences are noted by an asterisk. M indicates men; PFA, platelet function analyzer; and W, women.

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  Figure 4. Changes in platelet aggregation during the course of treatment. A, Platelet aggregation at 3 hours after first aspirin exposure was compared with baseline platelet aggregation, which is standardized and set at 0. Agonist concentrations are expressed in μmol/L for epinephrine (EPI) and ADP and as mg/mL for collagen (COL). Standard error bars are displayed. None of the 95% CIs for the individual values include 0, indicating a significant change in response over the time period. Significant differences between the sexes (P<0.05) are noted with a bracket and asterisk. B, Platelet aggregation after 4 weeks of aspirin treatment was compared with platelet aggregation 3 hours after the first aspirin dose, which is standardized and set at 0. Agonist concentrations are expressed in μmol/L for EPI and ADP and as mg/mL for COL. Standard error bars are displayed. Individual values for which the estimated 95% CI does not include 0 (indicating a significant change in response over the time period) are noted with an asterisk. Significant differences between the sexes (P<0.05) are noted with a bracket and asterisk. The data used to generate these figures are reported in Table S3. M indicates men;…

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  Figure 5. Platelet response to ex vivo aspirin exposure. Ex vivo aspirin exposure results in a decrease in platelet aggregation, with no significant sex differences. Values are standardized in comparison to baseline platelet aggregation, which is set at 0. Agonist concentrations are denoted above each frame and are expressed in μmol/L for epinephrine (EPI) and ADP and as mg/mL for collagen (COL). Standard error bars are displayed. M indicates men; and W, women.