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Circadian rhythms of fibrinogen and antithrombin III in liver cirrhosis
1Department of Internal Medicine and Public Health, School of Medicine and Surgery, University of L'Aquila, Italy.
Insights
Plasma fibrinogen and antithrombin III levels show daily circadian rhythms in healthy individuals and those with compensated liver cirrhosis. These rhythms are disrupted in decompensated cirrhosis, indicating disease progression.
Area of Science:
- Chronobiology
- Hepatology
- Coagulation Science
Background:
- Acquired deficiencies of fibrinogen and antithrombin III are common in liver cirrhosis.
- Plasma levels of these factors fluctuate throughout the day.
- Circadian rhythms of coagulation factors in cirrhosis are not well understood.
Purpose of the Study:
- To investigate the circadian rhythms of plasma fibrinogen and antithrombin III.
- To compare these rhythms in healthy controls, compensated cirrhosis patients, and decompensated cirrhosis patients.
Main Methods:
- Studied 3 groups: 10 healthy controls, 10 compensated cirrhosis, 10 decompensated cirrhosis patients.
- Measured plasma fibrinogen and antithrombin III every 3 hours over 24 hours.
- Analyzed time-series data using the mean-group cosinor method.
Main Results:
- Significant circadian rhythms for fibrinogen and antithrombin III were found in healthy controls and compensated cirrhosis patients (peaks in afternoon).
- No significant circadian rhythms were detected in decompensated cirrhosis patients.
- Significant differences in circadian rhythms were observed between all three groups for fibrinogen and between controls and both cirrhosis groups for antithrombin III.
Conclusions:
- Healthy individuals exhibit daily circadian rhythms for plasma fibrinogen and antithrombin III.
- Liver cirrhosis is associated with chronobiological alterations in the coagulation system.
- The degree of circadian rhythm derangement correlates with the stage of liver cirrhosis, potentially serving as an indicator of disease progression.
Background:
Since acquired deficiencies of fibrinogen and antithrombin III are reported in liver cirrhosis and it is known that their plasma levels fluctuate during the day, the circadian rhythms of plasma fibrinogen and plasma antithrombin III were investigated in patients with compensated and decompensated cirrhosis, compared to healthy controls.
Methods:
Three groups of subject were considered: (A) 10 healthy controls; (B) 10 patients with compensated liver cirrhosis; (C) 10 patients with decompensated liver cirrhosis. The fibrinogen and antithrombin III levels were determined in blood samples drawn in each studied subject during the span of a whole day and every three hours starting from midnight. The time-related data were analyzed by means of the "mean-group cosinor" method.
Results:
Significant (p < 0.05) circadian rhythms were detected for the two variables in groups A and B, with peaks in the afternoon hours. No significant (p > 0.05) rhythms were found for group C. A significant (p < 0.05) difference was found between the three groups regarding the circadian rhythm of fibrinogen, and between controls and patients with compensated cirrhosis and between compensated and decompensated patients regarding the circadian rhythm of antithrombin III.
Conclusions:
These data suggest that in healthy subjects the plasma levels of fibrinogen and antithrombin III present daily variations with own circadian rhythms, and that liver cirrhosis is associated with chronobiological circadian changes in the coagulation system, related to the stage of the disease. This progressive derangement could be considered as an index of evolution in the natural history of cirrhosis of the liver.