Natural anticoagulants, aging, and thromboembolism

Area of Science:

• Hematology
• Gerontology
• Physiology

Background:

• Normal aging impacts the human blood coagulation system, a concern due to the link between vascular disease and aging.
• Key coagulation factors (fibrinogen, factors VII, VIII, IX) and clotting activation markers (prothrombin fragment 1+2, fibrinopeptide A, thrombin-antithrombin III complex, D-dimer) increase with age in healthy individuals.

Purpose of the Study:

• To investigate age-related changes in both procoagulant and anticoagulant factors in the blood coagulation system.
• To explore the balance between procoagulant and anticoagulant factors in healthy aging, including centenarians.

Main Methods:

• Analysis of plasma concentrations of specific coagulation factors and natural anticoagulants.
• Correlation of biochemical markers of coagulation and activation with chronological age.
• Comparison of factor levels between young and elderly subjects, and across genders.

Main Results:

• Plasma levels of fibrinogen, factor VII, factor VIII, factor IX, high molecular-weight kininogen, and prekallikrein increase with age.
• Markers of in vivo clotting activation (prothrombin fragment 1+2, fibrinopeptide A, thrombin-antithrombin III complex, D-dimer) correlate positively with age.
• Antithrombin III, protein C, and free protein S levels increase with age. Heparin cofactor II decreases in the elderly. Tissue factor pathway inhibitor increases in women but not men.

Conclusions:

• Despite age-related increases in procoagulant factors and activation markers, healthy aging is characterized by a complex interplay with natural anticoagulants.
• Elevated levels of certain natural anticoagulants in older individuals may counterbalance the procoagulant changes, maintaining hemostatic balance.
• Centenarians exhibit hypercoagulability alongside a healthy state, suggesting robust compensatory mechanisms in extreme longevity.