The Role of Immobilized Phospholipids in the Initiation of Blood Coagulation under Flow Conditions

Localized thrombin generation appears to be a key event in the hemostatic response to the vascular injury. This protein leads to both irreversible platelet activation and formation of a fibrin mesh, which stabilizes the hemostatic plug. It is generally accepted that flow has a strong inhibitory effect on the kinetics of plasma coagulation reactions, so that thrombin generation and fibrin formation are restricted to the areas, which are protected from the diluting effect of blood flow, for example, the regions inside the platelet aggregate or in the subendothelial matrix. However, experimental evidence indicates the possibility of in vitro fibrin polymerization at arterial shear rates in the absence of platelets. Here using in vitro experiments and in silico models we show that the initiation of plasma coagulation under arterial shear rates can occur due to the presence of an immobilized phospholipid fraction in the area mimicking the damaged vascular wall. Our results suggest that binding of coagulation factors to these phospholipids allows the initial stages of plasma coagulation to be protected from the flow and leads to a rapid thrombin production even under conditions of arterial blood shear rates. Thus, the obtained data suggest that under some conditions the activation of secondary hemostasis may precede and promote platelet activation and aggregation.

Automated summary

This study found that plasma coagulation under arterial shear rates can be initiated by the presence of an immobilized phospholipid fraction in the damaged vascular wall. The binding of coagulation factors to these phospholipids protects the initial stages of plasma coagulation from flow and leads to rapid thrombin production even under arterial blood shear rates.