Summary
Recent observations describe an increase in platelet aggregability and a decrease
in fibrinolytic activity in the early morning hours. To determine whether anticoagulant
proteins also show such a circadian variation we measured protein C (PC), protein
S (PS), antithrombin (AT) and heparin cofactor-II (HC-II) levels on venous plasma
samples taken from 10 healthy men at three-hour intervals throughout a 24-hour period.
To investigate the possible temporal mapping of circadian periodicity, we also measured
plasma levels of beta-thromboglobulin (β-TG) as an indicator of platelet activation,
and interleukin-6 (IL-6) as one of the possible regulatory factors that drive this
rhythm.
Blood samples were drawn at 6 a.m., 9 a.m., noon, 3 p.m., 6 p.m., 9 p.m. and midnight.
PC, IL-6 and β-TG were measured by ELISA, PS and AT by latex immune assay and HC-II
by chromogenic substrate method. A significant circadian variation was found in PC,
PS, AT, β-TG and IL-6, but not in HC-II levels. PC, PS, IL-6 and β-TG were at their
peaks at 6 a.m., and nadirs at a time from noon to midnight. AT peak was at 6 p.m.
and nadir at noon. The regression of PS on IL-6 was significant. Although the fluctuations
of PS and AT were within the normal ranges during the day, some PC levels of two subjects
were below the lower normal limit (0.70).
These data indicate that PC, PS, and AT show a marked circadian periodicity as the
other components of the blood coagulation and fibrinolytic system do. The similar
trends in plasma concentrations of PC, PS, β-TG and IL-6 may be coincidental, but
could reflect a common regulatory mechanism or an effect on each other. The clinical
implications of these physiological changes in coagulation inhibitors and the role
of IL-6 in the anticoagulant response deserve further studies.
