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Circadian variation in platelet function in healthy volunteers
S M Jafri1, M VanRollins, T Ozawa
1Heart and Vascular Institute, Henry Ford Hospital, Detroit, Michigan 48202.
Insights
Circadian variation in hemostatic factors, specifically platelet activation markers beta-thromboglobulin and platelet factor 4, correlates with daily activity. Coagulation factors did not show significant diurnal changes.
Area of Science:
- Cardiovascular Physiology
- Hemostasis and Thrombosis
- Chronobiology
Background:
- Cardiac events exhibit a diurnal pattern, often peaking in the morning.
- Hemostatic factors, including platelet and coagulation systems, are implicated in cardiovascular events.
- Understanding circadian variations in hemostasis is crucial for explaining event timing.
Purpose of the Study:
- To investigate diurnal changes in platelet activation and coagulation.
- To determine if these changes correlate with daily activity patterns.
- To assess the role of circadian variations in hemostatic factors in morning cardiac events.
Main Methods:
- Measured in vitro platelet aggregability (epinephrine, adenosine diphosphate) in 9 healthy subjects.
- Assessed in vivo platelet activation using beta-thromboglobulin and platelet factor 4.
- Quantified coagulation activation via thrombin-antithrombin III complexes and D-Dimers.
- Collected measurements at different times throughout the day.
Main Results:
- Significant circadian variation observed in beta-thromboglobulin (p<0.05) and platelet factor 4 (p<0.06).
- Platelet activation markers peaked in the afternoon (3 P.M.) with activity, lowest when resting in the morning.
- No significant diurnal variation found in coagulation markers (thrombin-antithrombin III, D-Dimer) or platelet aggregability to adenosine diphosphate.
Conclusions:
- Circadian changes in platelet activation, indicated by beta-thromboglobulin and platelet factor 4, are linked to daily physical activity.
- Coagulation parameters do not exhibit significant diurnal variation in healthy individuals.
- Diurnal changes in platelet function, not coagulation, may contribute to the timing of hemostatic events.
Abstract:
Circadian variation in hemostatic factors may contribute to a higher frequency of cardiac events observed in the morning and with activity. Diurnal changes in these factors were investigated by measuring in vitro platelet aggregability in response to epinephrine and adenosine diphosphate together with beta-thromboglobulin and platelet factor 4 as indexes of in vivo platelet activation. Activation of coagulation was measured by thrombin-antithrombin III complexes and D-Dimers. Tests were performed in 9 normal healthy subjects. Circadian changes occurred in beta-thromboglobulin (p less than 0.05) and platelet factor 4 (p less than 0.06). Plasma levels of beta-thromboglobulin and platelet factor 4 were lowest with patients supine and resting at 7 and 8 A.M., and increased with activity, with peak levels achieved at 3 P.M. (p less than 0.01). Thrombin-antithrombin III complexes (p = 0.44), D-Dimer (p = 0.36) and in vitro platelet aggregability to adenosine diphosphate (p = 0.20) did not show diurnal variation. There was a trend toward circadian variation in vitro platelet aggregability to epinephrine, but these changes did not achieve statistical significance (p = 0.16). Circadian changes of in vivo release of beta-thromboglobulin and platelet factor 4 correlated to patient activity and not to the morning peaks in ischemic events. These data indicate that changes in platelet function and not in coagulation have a diurnal occurrence.