Koagulatorische Aktivität der Thrombozyten

Abstract

Haemostasis is the concerted action of blood components aimed at prevention of blood loss after vessel injury. Thrombosis is the other side of the coin, a misled physiological process, i.e. a haemostatic reaction occurring at a diseased vessel wall. Haemodynamic forces enrich platelets in a fluid boundary layer adjacent to the vessel wall where they flow along the endothelium scanning it for defects. Once the platelets detect an injury they immediately adhere--a process beginning with initial deceleration and attachment via glykoprotein (GP) Ibalpha receptor-binding to immobilized von Willebrand factor (VWF). The GPIb receptor requires no stimulation. This is in contrast to subsequently interacting receptors such as integrin alphaIIbbeta3 (GPIIb/IIIa), integrin alpha2beta1, and GP VI, which are activated via outside-in and inside-out signalling. The latter receptors bind to their respective ligands: VWF, fibrinogen, collagen and other subendothelial proteins. Upon the first layer of adherent platelets additional accrual of platelets is transient when mediated by VWF, but is then stabilized by fibrinogen bridging integrin alphaIIbbeta3 receptors on neighboring platelets. Such aggregates present a large mass of procoagulant membranes, the surface of which serves for complexation and activation of clotting factors. Thereby fibrin polymerization is accelerated manyfold. In addition, platelets contain mRNA for fast production of tissue factor, the most effective trigger of extrinsic coagulation. The formed fibrin fibers stabilize the platelet aggregates against detachment by shear forces. A shortened clotting time probably due to activated membranes was also found with microparticles generated at high shear rates through GPIb-VWF-interaction. Thus, platelets and platelet derived microparticles seem to play an important role not only in focussing the haemostatic response to the region of injury but also in initiating and accelerating the subsequent clotting reaction.