BACKGROUND: The fibrinogen Aalpha Thr312Ala polymorphism occurs within the alphaC domain of fibrinogen, which is important for lateral aggregation and factor XIII-induced cross-linking of fibrin fibers. We have previously shown an association of Ala312 fibrinogen with poststroke mortality in subjects with atrial fibrillation and with pulmonary embolism in subjects with venous thrombosis. METHODS AND RESULTS: We studied the properties of clots formed from purified Ala312 and Thr312 fibrinogen and found that Ala312 fibrinogen produces stiffer clots, associated with increased alpha chain cross-linking, as demonstrated by SDS-Page. On electron microscopy analysis, we found larger fiber diameters in the Ala312 clots and observed a lower number of fibers per square micrometer. The number of branch points per square micrometer was similar between genotypes. CONCLUSIONS: Our study shows that Ala312 influences clot structure and properties by increased factor XIII cross-linking and formation of thicker fibrin fibers. These findings may provide a mechanism by which Ala312 fibrinogen could predispose to clot embolization.
BACKGROUND: The fibrinogen Aalpha Thr312Ala polymorphism occurs within the alphaC domain of fibrinogen, which is important for lateral aggregation and factor XIII-induced cross-linking of fibrin fibers. We have previously shown an association of Ala312fibrinogen with poststroke mortality in subjects with atrial fibrillation and with pulmonary embolism in subjects with venous thrombosis. METHODS AND RESULTS: We studied the properties of clots formed from purified Ala312 and Thr312fibrinogen and found that Ala312fibrinogen produces stiffer clots, associated with increased alpha chain cross-linking, as demonstrated by SDS-Page. On electron microscopy analysis, we found larger fiber diameters in the Ala312 clots and observed a lower number of fibers per square micrometer. The number of branch points per square micrometer was similar between genotypes. CONCLUSIONS: Our study shows that Ala312 influences clot structure and properties by increased factor XIII cross-linking and formation of thicker fibrin fibers. These findings may provide a mechanism by which Ala312fibrinogen could predispose to clot embolization.
Authors: Lu-Chen Weng; Weihong Tang; Stephen S Rich; Nicholas L Smith; Susan Redline; Christopher J O'Donnell; Saonli Basu; Alexander P Reiner; Joseph A Delaney; Russell P Tracy; Cameron D Palmer; Taylor Young; Qiong Yang; Aaron R Folsom; Mary Cushman Journal: Thromb Res Date: 2014-05-20 Impact factor: 3.944
Authors: Laura J Rasmussen-Torvik; Mary Cushman; Michael Y Tsai; Yan Zhang; Susan R Heckbert; Wayne D Rosamond; Aaron R Folsom Journal: Thromb Res Date: 2007-04-11 Impact factor: 3.944
Authors: Sofian Metassan; Michael N Routledge; Andrew J Lucking; Shirley Uitte de Willige; Helen Philippou; Nicholas L Mills; David E Newby; Robert As Ariëns Journal: Part Fibre Toxicol Date: 2010-06-16 Impact factor: 9.400