Figure 3. The role of circadian variation in modulating haemostatic activity.

Levels of various procoagulant proteins, including fibrinogen and thrombomodulin, as well as fibrinolysis inhibitor PAI-1, vary with time of day, skewing the plasma and vessel surface environment in the morning towards procoagulant activity. Similarly, platelet and monocyte count increase in the morning, as is the expression of pro-adhesive cell surface receptors, such as PSGL-1. This can facilitate monocyte binding to platelet P-selectin to form aggregates, triggering increased TF activity on the monocyte surface. Collectively, circadian variation in plasma coagulation protein levels, innate immune cell number and activity, and vessel surface receptor composition may contribute to observed time-of-day effects on acute cardiovascular disease manifestation.