PubMed · 14780201
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L LORAND. 1950-10-21. Fibrin clots.. https://doi.org/10.1038/166694a0
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Platelets play a key role in hemostasis and thrombosis. The formation of a platelet plug is accompanied by the generation of thrombin, which results in the generation of fibrin required for stabilization of the platelet plug. Platelet plug formation and coagulation are closely linked processes. Thrombin is a potent platelet activator, which proceeds through proteolysis of the protease activated receptors (PARs). Furthermore, thrombin binds glycoprotein Ib(alpha), which amplifies platelet activation by accelerating PAR-1 activation, and possibly also by direct signaling events through glycoprotein Ib(alpha). Moreover, thrombin's specificity towards other substrates changes after binding glycoprotein Ib(alpha). Fibrinogen and fibrin, the end product of the coagulation cascade, are also involved in platelet aggregation. Both fibrinogen and fibrin bind the integrin alpha(IIb)beta(3), and another fibrin receptor involved in platelet aggregation has been postulated. This review will discuss the role of thrombin and fibrin(ogen) in platelet functioning, and will highlight pathways at the crossroad of coagulation and platelet functioning, which are potential targets for antithrombotic therapy.
The measurement of fibrin clot permeability is important in the investigation of fibrin clot characteristics. A major disadvantage of the standard measurement techniques is that they are time consuming as they require constant adjustments and monitoring. Presented here is a new method that is easy to perform and does not need continuous adjustments. In addition, the supervision required during the measurement is greatly minimized. When performing the measurement in quadruple, the intra-run coefficient of variation is 11.7%, which is comparable with other reported methods. A (5.1-13.1) x 10(-9) cm reference interval of the permeability coefficient (Ks) among 22 healthy volunteers was established.
Thrombolysis is conventionally regarded as dissolution of the fibrin matrix of thrombi by plasmin, a protease generated by plasminogen activators from its inactive precursor, plasminogen. Typically plasminogen activation occurs on the surface of the clot, where fibrin behaves as a cofactor in this process, and plasmin also initiates its proteolytic action at the fluid-solid interface. Although the basic reactions of the plasminogen/plasmin system in fluid phase are well characterized in terms of classical enzymology, they cannot explain completely the interfacial fibrinolytic events. Recently new methods have been introduced for quantitative evaluation of plasminogen activation on gel-phase fibrin and heterogenous-phase proteolysis, an overview of the new methodology is presented. Following formation of an interfacial lytic zone, fibrin dissolution proceeds through propagation of this zone to the core of the clot, which depends on diffusion and permeation phenomena affected by the composition of thrombi. Phospholipids (originating from platelets) form a diffusion barrier to the thrombolytic agents and also bind some of them; structural cellular proteins (namely myosin) interact with the fibrin fibers masking their cofactor and plasmin-cleavage sites. The contribution of these recent findings to our understanding of the limitations of current thrombolytic therapy is discussed. Finally, attention is focused on the termination of thrombus-associated proteolytic action in an environment abundant in proteinase inhibitors. Thus, combining together the interfacial events in the initiation, progress and termination of thrombolysis, a concept for modeling the thrombus as a temporary fibrinolytic compartment is presented.