Age-related Global Coagulation Changes: From Neonate to Old Age

Abstract Global coagulation assays provide a comprehensive assessment of clotting and fibrinolytic dynamics and have shown potential in predicting bleeding and thrombotic risk. Successful clinical implementation, however, requires understanding of normal age-specific changes, which remains limited. This study aims to evaluate age- and sex-related differences in global coagulation assays from neonates to older adults. A total of 546 citrated plasma samples from 380 healthy pediatric participants (0 to < 18 years) and 166 adults (20–79 years, without known cardiovascular risk factors or medications affecting coagulation) were tested for thrombin generation (CAT-TG), modified overall hemostatic potential (mOHP), and plasmin generation (PG). This study demonstrated that hemostatic capacity was lowest at birth and increased rapidly throughout early childhood, with endogenous thrombin and plasmin potentials peaking in the fourth decade of life. Fibrin generation continued to rise, peaking in the sixth decade, accompanied by a decline in fibrinolytic capacity. Sex differences showed a hypercoagulable shift in females beginning at puberty, peaking during the reproductive years. These sex differences attenuated post-menopause, reflecting the convergence of cardiovascular risk in older age. These findings provide essential normative data to support age- and sex-adjusted interpretation of global coagulation assays. Overall, the most pronounced hemostatic changes occur in early life, consistent with developmental hemostasis. The midlife peak in procoagulant parameters and the decline in fibrinolytic capacity highlight progressive hemostatic changes associated with aging. While sex-related differences underscore the role of endogenous hormones in modulating coagulation, longitudinal studies in healthy and at-risk individuals are warranted to clarify trajectories and inform personalized interventions.