Age dependence of blood fibrinolytic components and the effects of low-dose oral contraceptives on coagulation and fibrinolysis in teenagers

Abstract

Basal t-PA antigen concentration, PAI-I activity and fibrinolytic capacity was studied in plasma from 20 healthy teenager girls (age 15.9 +/- 1.3 years) and two groups of older healthy volunteers, consisting of 17 women (age 32 +/- 8 years, group 1) and 35 men (age 34 +/- 8 years, group 2). Basal t-PA antigen concentrations in plasma were found to be highly age-dependent with higher values with increasing age. The teenager girls had significantly lower values compared with the two groups of elderly volunteers. PAI-I levels were significantly higher in plasma from the teenager girls and the fibrinolytic capacity after 15 min of venous occlusion was significantly lower. In this study we also determined the effect of low-dose oral contraceptives (OC) on coagulation and fibrinolysis in the teenager group. Each teenager served as her own control with samples drawn before and on OC after 4 months of use. The coagulation parameters, factor VIII activity, AT III, Protein C and platelet counts were all within reference values before and on OC. The fibrinolytic activity in plasma after venous occlusion (15 min) increased significantly when the teenagers had used OC for 4 months. This phenomenon was explained by significantly decreased PAI levels and also by significantly increased t-PA antigen release from the vessel wall after venous occlusion.

PIP: The effect of high and low-dose oral contraceptives (OCs) on the fibrinolytic system remains controversial, although disturbances in this system are associated with the development of venous thrombosis. It has been suggested that this may be due to either a decreased synthesis of vessel wall tissue plasminogen activator (t-PA) or a defective release of t-PA from the vessel wall. Defective fibrinolysis can also be due to increased concentration of tissue plasminogen activitor inhibitor (PAI-I). This studied utilized new and improved methods for t-PA and PAI-I measurements in plasma to: study basal fibrinolytic activity, basal t-PA antigen concentration, and PAI-I in plasma from teenagers to assess whether these parameters are age-dependent; 2) evaluate the influence of low-dose OCs on the fibrinolytic components; and 3) study possible variations in some coagulation factors. Plasma were obtained from 20 healthy female adolescents (mean age 16 years), 17 health adult women (mean age 32 years) and 35 healthy adult males (mean age 34 years). Basal t-PA antigen concentrations plasma were highly age dependent, with higher values with increasing age. The fibrinolytic capacity was also lower in the younger women, while PAI-I levels were higher. This finding suggests a need for age- and sex-matched controls in studies of the components of fibrinolysis in plasma. 4 months of OC use did not affect coagulation parameters, factor VIII activity, AT III, Protein C, or platelet counts. However, fibrinolytic activity in plasma after venous occlusion (15 minutes) increased significantly in teenagers who used OCs for 4 months. This finding was explained by significantly decreased PAI levels and increased t-PA antigen release from the vessel wall after venous occlusion.