Diurnal changes of fibrinolysis in patients with liver cirrhosis and esophageal varices

Variceal bleeding, whose triggering mechanisms are largely unknown, occurs with a circadian rhythmicity, with 2 peaks, one greater, in the evening, an d one smaller, in the early morning. We assessed some clotting and hemodyna mic parameters, possibly involved in variceal hemorrhage, over a 24-hour pe riod, at 4-hour intervals, in 16 patients with cirrhosis and esophageal var ices and in 9 controls. At each time interval, tissue plasminogen activator (tPA) and tPA inhibitor-1 (PAI-1) antigens and activities and total euglob ulin fibrinolytic activity were determined and portal-vein flow velocity, v olume, and congestion index were measured by duplex-Doppler. Significant ci rcadian rhythms were searched for by least-squares and cosinor methods. tPA activity showed a circadian rhythm in cirrhosis, with a peak of 2.85 times the trough value, calculated at 18:42, and remained over 2.5-fold until sh ortly after 22:00, Total fibrinolytic activity showed a similar pattern, wh ich was statistically significant also in controls. tPA and PAI antigens al so showed significant circadian rhythm both in controls and cirrhotics, wit h higher values in the morning. Among the portal hemodynamic parameters onl y the congestion index showed significant rhythmic changes and only in cirr hosis, with the highest values in the late evening, but with limited diurna l excursion (+/- 5.5%). In conclusion, we showed the existence of a circadi an rhythm of fibrinolysis in cirrhosis, whose temporal distribution might s uggest a role of fibrinolysis in variceal hemorrhage on the basis of the co mparison to the known chronorisk of variceal bleeding.