alexa Acute Cardiology Online Journals | OMICS International | Emergency Medicine: Open Access

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Acute Cardiology

Fibrin provides the structural backbone to the developing blood clot or thrombus. The structure of the fibrin clot is a major determinant of the mechanical characteristics of the clot and of the resistance of the clot to fibrinolysis. Clinical studies consistently show that patients with thrombotic diseases form fibrin clots with increased fibre density and small pores that have increased resistance to lysis by tPA and plasmin. Abnormal fibrin clot structure contributes to the thrombotic burden in patients with cardiovascular diseases. The amount of thrombin and fibrinogen influence the final structure of the fibrin clot. However, there are a number of other mechanisms that regulate fibrin clot structure independently of thrombin and fibrinogen concentrations. For example, splice variation of the fibrinogen gamma chain regulates fibrin clot structure by directly interfering with protofibril formation as demonstrated by atomic force microscopy. The clots produced by the variant show reduced rigidity using magnetic tweezers but increased resistant to fibrinolysis. The effects of gamma prime splice variation on fibrin clot structure are also evident at physiological levels in plasma as observed in the PURE study. In addition, we have evidence that the contact pathway of coagulation influences fibrin clot structure, independently of its role in thrombin generation, and that factor XIII does not merely crosslink an already established structure but actively regulates fibrin clot structure. Elucidation of the mechanisms that regulate fibrin structure may provide new opportunities for the diagnosis of, or therapeutic intervention with, thrombosis. Robert A. S. Ariens, Mechanisms modulating fibrin clot structure and thrombosis
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Last date updated on June, 2014

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