Prothrombin conversion accelerates with increasing age in women but not in men: findings from the Moli-sani Cohort Study

Figures

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  Figure 1. Flow chart for sample selection and analysis. TG, thrombin generation; TD, thrombin dynamics.

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  Figure 2. Thrombin dynamics parameters quantified after stimulation with PPP Reagent Low, stratified for age and sex. Thrombin dynamics parameters total prothrombin conversion (PCtot; A), maximal prothrombin conversion rate (PCmax; B), thrombin-antithrombin complexes (T-AT; C), thrombin-α2-macroglobulin complexes (T-α2M; D) according to the different age categories in the Moli-sani cohort. Data are depicted as the median and interquartile range (box), and the 2.5th to 97.5th percentile interval (whiskers). Data was stratified for sex, showing the data for men in blue and women in pink. Age categories were compared by ANOVA analysis with Bonferroni post hoc testing, with the 35 to 44 years as reference, separately for men (blue asterisks) and women (pink asterisks). Additionally, the difference between men and women in the same age category is shown as black asterisks. Asterisks denote the corresponding P-value thresholds: ∗P < .05, ∗∗P < .01, ∗∗∗P < .001, ∗∗∗∗P < .0001.

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  Figure 3. Thrombin dynamics parameters quantified after stimulation with PPP reagent, stratified for age and sex. Thrombin dynamics parameters total prothrombin conversion (PCtot; A), maximal prothrombin conversion rate (PCmax; B), thrombin-antithrombin complexes (T-AT; C), thrombin-α2-macroglobulin complexes (T-α2M; D) according to the different age categories in the Moli-sani cohort. Data are depicted as the median and interquartile range (box), and the 2.5th to 97.5th percentile interval (whiskers). Data was stratified for sex, showing the data for men in blue and women in pink. Age categories were compared by ANOVA analysis with Bonferroni post hoc testing, with the 35 to 44 years as reference, separately for men (blue asterisks) and women (pink asterisks). Additionally, the difference between men and women in the same age category is shown as black asterisks. Asterisks denote the corresponding P-value thresholds: ∗P < .05, ∗∗P < .01, ∗∗∗P < .001, ∗∗∗∗P < .0001.

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  Figure 4. Thrombin decay constant in men and women, stratified for age. Data are depicted as the median and interquartile range (box), and the 2.5th to 97.5th percentile interval (whiskers). Data was stratified for sex, showing the data for men in blue and women in pink. Age categories were compared by ANOVA analysis with Bonferroni post hoc testing, with the 35 to 44 years as reference, separately for men (blue asterisks) and women (pink asterisks). Additionally, the difference between men and women in the same age category is shown as black asterisks. Asterisks denote the corresponding P-value thresholds: ∗P < .05, ∗∗P < .01, ∗∗∗P < .001, ∗∗∗∗P < .0001.

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  Figure 5. Thrombomodulin sensitivity of thrombin dynamics quantified after stimulation with PPP reagent, stratified for age and sex. Inhibition of total prothrombin conversion (PCtot) in men versus women. Data are depicted as the median and interquartile range (box), and the 2.5th to 97.5th percentile interval (whiskers). Data was stratified for sex, showing the data for men in blue and women in pink. Age categories were compared by ANOVA analysis with Bonferroni post hoc testing, with the 35 to 44 years as reference, separately for men (blue asterisks) and women (pink asterisks). Additionally, the difference between men and women in the same age category is shown as black asterisks. Asterisks denote the corresponding P-value thresholds: ∗P < .05, ∗∗P < .01, ∗∗∗P < .001, ∗∗∗∗P < .0001.

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  Figure 6. Thrombin dynamics parameters and thrombomodulin sensitivity in women between the age of 35 and 54 years, stratified for OC use. (A–B) Total prothrombin conversion after stimulation with PPP Reagent Low (A) or PPP Reagent (B). (C–D) Maximum prothrombin conversion rate after stimulation with PPP Reagent Low (C) or PPP Reagent (D). (E–F) Thrombin-antithrombin complex formation after stimulation with PPP Reagent Low (E) or PPP Reagent (F). (G–H) Thrombin-α2-macroglobulin complex formation after stimulation with PPP Reagent Low (G) or PPP Reagent (H). (I) Thrombin decay capacity. (J) Inhibition of total prothrombin conversion by thrombomodulin. Data are depicted as the median and interquartile range (box), and the 2.5th to 97.5th percentile interval (whiskers). Data was stratified for OC use and age category, as indicated on the X-axis. The effect of OC use in each age category was assessed by a T-test. Asterisks denote the corresponding P-value thresholds: ∗P < .05, ∗∗P < .01, ∗∗∗P < .001, ∗∗∗∗P < .0001.