Phospholipid Topography Coagulation

Phospholipids play a role in thrombin generation because the constitute the support on which both the factor X activating enzyme (“tenase”) and the prothrombin activating enzyme (proth rcmbinase) are built.

In model systems with pure synthetic phospholipids it can be shown that the binding of the coagulation factors to a phospholipid surface is a function of both phospholipid charge and membrane fluidity. A relatively high molefraction of phosphatidyl serine (PS) is a prerequisite for optimal binding of the vitamin K dependant factors. Precise measurements on the binding constant and the number of binding sites of factor X show that at molefractions of PS between 0.01 and 0.25 aproximately one PS binds per Gla-residue. Above 0.25% of PS vesicle agregation occurs.

The normal intact circulating platelet shows a molefraction of PS of ̴ 0.03 in the outer leaf let of its plasma membrane and therefore hardly if at all stimulates thrombinformation.

Upon activation by thrombin (2nM) together with collagen, (10μg/ml) the outer leaflet aquires increasing amounts of PS without platelet disruption taking place.

This suggests a flip-flop movement of phospholipids across the membrane as part of the activation reaction of platelets. It can be shown that optimal “tenase” supporting phospholipid compositions appear before prothrombine supporting ones. The activation by thrombin and collagen is only partly inhibited by prostacyclin even at high concentrations.