title: Characteristics of fibrin formation and clot stability in individuals with congenital type IIb protein C deficiency.
abstract: Many studies have shown that unregulated or excessive thrombin formation is potentially a cause of thrombosis; however, studies examining processes that contribute to fibrin stabilization in individuals predisposed to thrombosis are limited. In this study, we investigate a family with familial thrombosis via type IIb protein C (PC) deficiency. Using contact pathway inhibited whole blood, thrombin generation, fibrin clot formation and factor (f)XIII activation were monitored over time in control (n=5) and PC deficient (n=4, 34 - 69% PC by activity) subjects. The dynamics of thrombin generation varied significantly with the time required to reach the maximal rate of thrombin-antithrombin formation being much shorter in PC deficiency (5.8 ± 0.4 minutes) than in controls (9.7 ± 0.4 minutes; p < 0.001). PC deficient clots were significantly heavier than control clots (p < 0.001) and this difference could not be contributed exclusively to differences in fibrinogen levels between groups. FXIII was consumed faster in PC deficient subjects (23.7 ± 2.0 nM/minute) than in controls (5.1 ± 1.5 nM/minute; p < 0.0001) suggesting increased fXIII activation and incorporation of fXIIIa substrates into the clot. In plasma, the clot lysis time was increased in PC deficiency by both TAFIa dependent and independent mechanisms. Since PC deficient clots are both denser and show a greater degree of resistance to fibrinolysis, these clots would likely resist fibrinolysis and potentiate fibrin deposition observed in thrombosis.
authors.affiliation: Department of Biochemistry, University of Vermont, Burlington, United States.
authors.forename: J H
authors.initials: JH
authors.lastname: Foley
authors.forename: L
authors.initials: L
authors.lastname: Ferris
authors.forename: K E
authors.initials: KE
authors.lastname: Brummel-Ziedins
mesh_terms: D000328:Adult; D000368:Aged; D001777:Blood Coagulation; D005260:Female; D005337:Fibrin / Q000096:biosynthesis*; D006801:Humans; D008297:Male; D020151:Protein C Deficiency / Q000151:congenital* / Q000378:metabolism*
chemical_list: D005337:Fibrin