Thrombosis fibrinogen

Thrombin, a serine protease, cleaves fibrinogen into fibrin to create a fibrous plug and also amplifies its own production through the activation of factor XI and cofactors V and Vlll. Thrombin also plays a crucial role in the activation of platelets through the cleavage of the protease-activated receptors on the platelet surface. Antagonists of G-protein-coupled protease-activated receptor PARi have been synthesised to study the role of thrombin PARi receptor in thrombosis and vascular injury. Thrombosis is the most common cause of death in the industrialised world and, whether through venous thromboembolism, myocardial infarction or stroke, ultimately involves the inappropriate activity of... 

Detection of thrombus is another clinically important goal. Contrast enhancement of vascular thrombosis has been achieved with a microbubble having a small peptide covalently attached to its surface that selectively binds to the GPIIb/llla fibrinogen receptor expressed on the surface of activated platelets that attach to thrombi. 

CE134 Costhuizen, W., H. H. Vorster, J. C. Jerling, et al. Both fish oil and olive oil lowered plasma fibrinogen in women with high baseline fibrinogen levels. Thrombosis Homeostasis 1994 72(4) 557-562. 

Injections of 131I given to detect pulmonary embolism can result in false-negative results in the 12SI-labeled fibrinogen test for venous thrombosis. 

The involvement of fibrinogen in biological functions beyond hemostasis and thrombosis is a wide open field. Nearly all research has been carried out with human fibrinogen, with isolated studies of a few other mammals, frog, chicken, zebrafish, and lamprey. There have been few comparative and evolutionary studies. 

Hantgan, R. R., Simpson-Haidaris, P. J., Francis, C. W., and Marder, V. J. (2000). Fibrinogen structure and physiology. In Hemostasis and Thrombosis Basic Principles and Clinical Practice (R. W. Colman, J. Hirsh, V. J. Marder, A. W. Clowes, andj. N. George, Eds.), pp. 203-232. Lippincott, Williams Wilkins, Philadelphia. 

The saliva of the medicinal leech contains a battery of substances that interfere with the hemostatic mechanisms of the host. One of these compounds is hirudin, a potent anticoagulant, which maintains the fluidity of the ingested blood and is the most potent inhibitor of thrombin. Upon binding to thrombin, the cleavage of fibrinogen and subsequent clot formation are prevented. The potency and specificity of hirudin make it a useful antithrombin-III-independent alternative to heparin for the control of thrombosis. 

Common risk factors for developing branch retinal vein thrombosis (BRVT) and central retinal vein thrombosis (CRVT) include increased plasma fibrinogen, diabetes, decreased exercise, hypertension, and hyperviscosity (205). Sickle cell anemia, polycythemia vera, and other proliferative disorders may also lead to this syndrome. 

In the initial study described by Gold et al. (1984), recombinant t-PA was characterized for its ability to lyse 2-hour-old thrombi. Tissue plasminogen activator was infused at doses of 4.3, 10, and 25 (ig/kg/min, i.v, and resulted in reperfusion times of 40, 31, and 13 minutes, respectively. Thus, in this model of canine coronary thrombosis, t-PA exhibited dose-dependent coronary thrombolysis. Furthermore, it is possible to study the effect of different doses of t-PA on parameters of systemic fibrinolytic activation, such as fibrinogen, plasminogen, and a2-antiplasmin, as well as to assess myocardial infarct size. For example, Kopia et al. (1988) demonstrated that SK elicited dose-dependent thrombolysis in this model. 

KO mice appeared to develop normally macroscop-ically, but possessed obvious signs of bleeding and thrombosis did not survive beyond 24 h after delivery microvascular thrombosis in the brain and necrosis in the liver plasma clottable fibrinogen was not detectable suggesting fibrinogen depletion and secondary consumptive coagulopathy (Jalbert et al. 1998). 

Denis C, Methia N, Frenette PS et al. (1998) A mouse model of severe von Willebrand disease defects in hemostasis and thrombosis. Proc Natl Acad Sci USA 95 9524-9529 Ni H, Denis CV, Subbarao S et al. (2000) Persistence of platelet thrombus formation in arterioles of mice lacking both von Willebrand factor and fibrinogen. J Clin Invest 106 385-392... 

Bostwick JS, Kasiewski CJ, Chu V et al. (1996) Anti-thrombotic activity of RG13965, a novel platelet fibrinogen receptor antagonist. Thrombosis Research 82 495-507... 

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