Effect of age, sex, and diurnal variation on the human fibrinolytic system

Abstract

SYNOPSiS Fibrinolytic activity, as shown by the dilute blood clot lysis time, tends to show a diurnal variation, but is relatively unaffected by age and sex.Mean plasma anti-urokinase activity is consistently and significantly greater in females in the post-menstrual week than in age-matched males, but is relatively unaffected by daily variation and age. This sex difference in the activity of plasma, which is inhibitory to fibrinolysis, is of a degree which makes this measurement important in studies of the fibrinolytic system in healthy persons and disease states.This communication reports the results of a study to determine the effect of age, sex, and diurnal variation on the fibrinolytic activity of blood, and the activity of plasma which is inhibitory to urokinase-activated fibrinolysis.Dissolution of fibrin by the fibrinolytic system depends upon the generation of a proteolytic enzyme, plasmin, from an inactive plasma precursor, plasminogen (Christensen and MacLeod, 1945). Plasminogen activation in blood is due to a heatlabile activator which can be demonstrated in subjects under physiological circumstances (Fearnley, Revill, and Tweed, 1952; Flute, 1960a and b;Sawyer, Fletcher, Alkjaersig, and Sherry, 1960). Free plasmin cannot be detected in the circulating blood, even in the presence of free activator (Sherry, Lindemeyer, Fletcher, and Alkjaersig, 1959;Sawyer, Alkjaersig, Fletcher, and Sherry, 1960), for such plasmin is rapidly neutralized by circulating antiplasmins, of which two types have been described (Norman, 1958; Norman and Hill, 1958).The human antiplasmin which migrates electrophoretically with the alpha-2 globulins combines rapidly and reversibly with plasmin (Norman, 1960) and predominates in inhibitory effect over the alpha-1 migrating antiplasmin (Mann, Cotton, and Jackson, 1966). Plasmin-antiplasmin neutralization may be, therefore, predominantly rapid and reversible, so forming a neutralized complex existing as a reservoir of fibrinolytic enzyme which can dissociate in the presence of fibrin (Ambrus and Markus, 1960).The present study has been undertaken in order to

Impairment of the Diurnal Fibrinolytic Response in Man

“…However, our results indicated that the failure to demonstrate a difference could have resulted from using one resting sample taken early in the day as the basis for comparison or from studying an abbreviated diurnal response that did not include peak fluctuations (14,29). For example, if only 8 AM resting levels of fibrinolytic activity had been compared in the present study, it would have appeared that blood fibrinolytic activity was unaltered by the aging process (Table 1).…”

“…The conflicting results of several other studies (13,14,29) in which the effects of aging on fibrinolysis were examined may have been due, in some instances, to differences in the assay systems used to measure the fibrinolytic activity. However, our results indicated that the failure to demonstrate a difference could have resulted from using one resting sample taken early in the day as the basis for comparison or from studying an abbreviated diurnal response that did not include peak fluctuations (14,29).…”

Fibrinolytic Activity in Animals of Different Species

“…Besides diurnal variation [Mann, 1967] several other factors like trauma, stress and physical exercise increase natural fibrinolytic activity in man [Fearnley, 1964]. The effect of these factors was not studied in the present investigations.…”

Studies On Fibrinolytic Activity in Normal Persons and Patients With Atherosclerotic Vascular Dis Ease After Physical Activity and Injections of Nicotinic Acid

“…[22][23][24] Plasminogen was estimated according to Alkjaersig et al 20 using the casein method. The results are expressed in percentages of normal.…”