Exercise-induced changes in hemostasis markers in marathon runners: effects of enzyme supplementation and determinants.

Background: Increases in hemostatic markers, indicators of thrombotic risk, have been reported following strenuous exercise; however, determinants of these responses remain poorly understood. This study aimed to determine whether supplementation with hydrolytic enzymes and flavonoids (Wobenzym Methods: This predefined subanalysis of the Enzy-MagIC trial was conducted within a prospective, randomized, double-blind, placebo-controlled trial. Participants were randomized (1:1) to receive WOB (rutoside 600-1200 mg/day, bromelain 540-1080 mg/day, trypsin 288-576 mg/day) or placebo for 1 week before and 2 weeks post-race, following a predefined dosing regimen. Blood samples were collected at baseline, immediately, 24 h, and 72 h post-race for analysis of D-dimer, plasminogen activator inhibitor-1 (PAI-1), tissue plasminogen activator (tPA), prothrombin fragment 1 + 2 (F1+2), thrombin generation (calibrated automated thrombography; CAT: lag time, peak thrombin, endogenous thrombin potential [ETP]), maximal platelet aggregation induced by adenosine diphosphate (MPADP), and platelet count. Results: Among 118 male runners (age 42 ± 11 years; WOB n = 64, placebo n = 54), no differences were observed between groups for any hemostatic marker (all p>0.05). D-dimer, PAI-1, tPA, F1+2, MPADP, and platelet count increased immediately post-race (all p<0.001) and returned toward baseline within 24 h. CAT lag time and peak thrombin increased at 24 h (both p<0.05), whereas ETP decreased immediately post-race (p<0.001). In multivariable analyses, ΔtPA was associated with finishing time and age, and ΔCAT lag time with body fat percentage (all p<0.05). Conclusion: WOB supplementation did not affect post-race hemostasis; however, marathon running induced hemostatic activation, partly driven by clinical and performance-related characteristics.