INTRODUCTION: More than 80% of cerebrovascular events are ischemic and largely thromboembolic by nature. We evaluated whether plasma factor composition and thrombin generation dynamics might be a contributor to the thrombotic phenotype of ischemic cerebrovascular events. MATERIALS AND METHODS: We studied (1) 100 patients with acute ischemic stroke (n=50) or transient ischemic attack (TIA) (n=50) within the first 24 hours from symptom onset, and (2) 100 individuals 1 to 4 years following ischemic stroke (n=50) or TIA (n=50). The tissue factor pathway to thrombin generation was simulated with a mathematical model using plasma levels of clotting factors (F)II, V, VII, VIII, IX, X, antithrombin and free tissue factor pathway inhibitor (TFPI). RESULTS: The plasma levels of free TFPI, FII, FVIII, and FX were higher, while antithrombin was lower, in the acute patients compared to the previous event group (all p≤0.02). Thrombin generation during acute events was enhanced, with an 11% faster maximum rate, a 15% higher maximum level and a 26% larger total production (all p<0.01). The increased thrombin generation in acute patients was determined by higher FII and lower antithrombin, while increased free TFPI mediated this effect. When the groups are classified by etiology, all stroke sub-types except cardioembolic have increased TFPI and decreased AT and total thrombin produced. CONCLUSION: Augmented thrombin generation in acute stroke/TIA is to some extent determined by altered plasma levels of coagulation factors.
INTRODUCTION: More than 80% of cerebrovascular events are ischemic and largely thromboembolic by nature. We evaluated whether plasma factor composition and thrombin generation dynamics might be a contributor to the thrombotic phenotype of ischemic cerebrovascular events. MATERIALS AND METHODS: We studied (1) 100 patients with acute ischemic stroke (n=50) or transient ischemic attack (TIA) (n=50) within the first 24 hours from symptom onset, and (2) 100 individuals 1 to 4 years following ischemic stroke (n=50) or TIA (n=50). The tissue factor pathway to thrombin generation was simulated with a mathematical model using plasma levels of clotting factors (F)II, V, VII, VIII, IX, X, antithrombin and free tissue factor pathway inhibitor (TFPI). RESULTS: The plasma levels of free TFPI, FII, FVIII, and FX were higher, while antithrombin was lower, in the acute patients compared to the previous event group (all p≤0.02). Thrombin generation during acute events was enhanced, with an 11% faster maximum rate, a 15% higher maximum level and a 26% larger total production (all p<0.01). The increased thrombin generation in acute patients was determined by higher FII and lower antithrombin, while increased free TFPI mediated this effect. When the groups are classified by etiology, all stroke sub-types except cardioembolic have increased TFPI and decreased AT and total thrombin produced. CONCLUSION: Augmented thrombin generation in acute stroke/TIA is to some extent determined by altered plasma levels of coagulation factors.
Authors: Claes Ladenvall; Ann Gils; Katarina Jood; Christian Blomstrand; Paul J Declerck; Christina Jern Journal: Arterioscler Thromb Vasc Biol Date: 2007-02-01 Impact factor: 8.311
Authors: Kathleen E Brummel-Ziedins; Thomas Orfeo; Matthew Gissel; Kenneth G Mann; Frits R Rosendaal Journal: PLoS One Date: 2012-01-11 Impact factor: 3.240
Authors: Renáta Hudák; Edina G Székely; Katalin R Kovács; Attila Nagy; Gergely Hofgárt; Ervin Berényi; László Csiba; János Kappelmayer; Zsuzsa Bagoly Journal: PLoS One Date: 2017-07-10 Impact factor: 3.240
Authors: Kathleen E Brummel-Ziedins; Thomas Orfeo; Peter W Callas; Matthew Gissel; Kenneth G Mann; Edwin G Bovill Journal: PLoS One Date: 2012-09-12 Impact factor: 3.240
Authors: Kathleen E Brummel-Ziedins; Matthew Gissel; Jacqueline Neuhaus; Álvaro H Borges; David R Chadwick; Sean Emery; James D Neaton; Russell P Tracy; Jason V Baker Journal: Res Pract Thromb Haemost Date: 2018-09-11