Thrombolytic Potential of N -Acetylcysteine

Article, see p 646 The development of occlusive arterial thrombus involves an exaggerated and unregulated extension of the events that occur during the generation of a physiological hemostatic barrier. These events are initiated by the interaction of the multimeric glycoprotein, von Willebrand factor (VWF) binding to elements in the damaged vessel wall and to the resting platelet receptor, glycoprotein Ib (GpIb).1 After initial unstable adhesion of platelets to the area of damage, platelets are activated, undergo shape change, and, on exposure of the GpIIb/IIIa integrin, develop stable aggregates mediated by integrin cross-linking through fibrinogen and VWF. This primary platelet plug is simultaneously stabilized by the generation of thrombin and subsequent deposition of an insoluble fibrin clot that reduces the risk of platelet plug removal. The role of VWF in this process is essential. Quantitative and qualitative pathologies of VWF result in the common inherited bleeding disorder, von Willebrand disease (VWD),2 and increased plasma levels of VWF are associated with an increased risk of both arterial and venous thromboembolism.3,4 In this issue of Circulation , Martinez de Lizarrondo et al5 report the results of using a VWF modifying agent to mitigate the development of arterial thrombosis. During its biosynthesis, VWF undergoes a number of critical posttranslational modifications. The generation of high-molecular-weight (HMW) multimers of the VWF monomer is crucial for mediating efficient platelet plug formation. These molecules are generated in the Golgi and are …