Circadian Rhythms of Fibrinogen, Antithrombin III and Plasminogen in Chronic Liver Diseases of Increasing Severity

Abstract

Acquired deficiencies of fibrinogen, antithrombin III and plasminogen are reported in liver disease, and it is known that their plasma levels fluctuate during the day. The aim of this study was to investigate the circadian rhythms of these three factors in chronic liver disease. Five groups of subjects were considered: (A) 15 healthy controls; (B) 15 patients with hepatic alcoholic steatosis; (C) 15 patients with chronic active hepatitis; (D) 15 patients with compensated cirrhosis of the liver, and (E) 15 patients with decompensated cirrhosis with ascites. The levels of fibrinogen, antithrombin III and plasminogen were determined in blood samples drawn in each subject during the span of a day every 3 h starting from midnight. The time-related values were analyzed using the ‘population-mean cosinor’ method. Groups A and B presented a significant (p < 0.05) circadian rhythm for each variable, group C a significant (p < 0.05) circadian rhythm for fibrinogen and antithrombin III and groups D and E no significant (p > 0.05) circadian rhythms. Statistically significant differences (p < 0.05) were demonstrated among the groups in the mean daily levels of the three variables by ANOVA, the concentrations decreasing with disease severity. These data confirm the existence of a significant diurnal periodicity in the circulating levels of fibrinogen, antithrombin III and plasminogen in controls and suggest that liver disease is associated with progressive circadian modifications in the temporal structure of fibrinogen, antithrombin III and plasminogen, related to the stage of the liver disease. The rhythm derangements may be considered markers of evolution in liver disease.

Diurnal, Seasonal, and Blood-Processing Patterns in Levels of Circulating Fibrinogen, Fibrin D-Dimer, C-Reactive Protein, Tissue Plasminogen Activator, and von Willebrand Factor in a 45-Year-Old Population

“…The diurnal variation in fibrinogen in middle-aged adults agrees with previous studies on much smaller samples 22,23,31 and shows a peak in the early afternoon, with values that decrease throughout the rest of the day. Previous studies of D-dimer on a small number of subjects (nϽ15) did not find a diurnal variation in D-dimer, 24,25 although another small study did report a morning peak.…”

“…8 This is supported by other smaller studies. 7,16 As well as seasonal effects, variable reports exist of a diurnal pattern in fibrinogen 12,22,23 and D-dimer, 24 -26 whereas t-PA shows a morning peak with levels that tend to decline during the day; 12,24,27,28 vWF has been reported to show no diurnal variation in 1 small study. 28 Diurnal variation may be an important source of heterogeneity or bias, and standardization for sampling time may be important in populationbased studies, as well as in using these variables for additional coronary heart disease risk prediction in individuals.…”

The Effect of Acute Training and Circadian Rhythm on Blood Hemostasis in Female Athletes

“…17,18 Some research has reported that the circadian rhythm is effective on the fibrinogen and plasminogen. 19,20 In a study by Kanabrocki et al, platelet and fibrinogen aggregation were reported in the afternoon and in the morning, respectively. 21 Yasuda et al stated that the thromboplastin time had a significant reduction in two of the four intervals studied.…”

Circadian Variation within Hemostasis: An Underrecognized Link between Biology and Disease?

“…Pasqualetti et al also reported a circadian rhythm in AT activity, with an acrophase in the early afternoon hours. 108 Because the intraindividual and within-day variability of these parameters is reportedly higher than the corresponding intra-assay variability, these changes might be real and reflect a significant daily fluctuation. At variance with these studies, however, Akiyama et al 101 did not observe any circadian variation in PC and AT levels.…”