Identification and characterization of novel mutations implicated in congenital fibrinogen disorders.

Introduction: Fibrinogen is a complex molecule comprised of two sets of Aα, Bβ, and γ chains. Fibrinogen deficiencies can lead to the development of bleeding or thromboembolic events. The objective of this study was to perform DNA sequence analysis of patients with clinical fibrinogen abnormalities, and to perform genotype-phenotype correlations.

Effects of anti-β2GPI antibodies on VWF release from human umbilical vein endothelial cells and ADAMTS13 activity.

Background: Antiphospholipid syndrome (APS) is characterized by recurrent thromboembolic events in the setting of pathologic autoantibodies, some of which are directed to β2-Glycoprotein 1 (β2GPI). The mechanisms of thrombosis in APS appear to be multifactorial and likely include a component of endothelial activation. Among other things, activated endothelium secretes von Willebrand factor, a hemostatic protein that in excess can increase the risk of thrombosis.

Mutations in the D'D3 region of VWF traditionally associated with type 1 VWD lead to quantitative and qualitative deficiencies of VWF.

Type 1 von Willebrand disease (VWD) is characterized by low plasma levels of von Willebrand factor (VWF) and clinical bleeding. Several mechanisms have been described that cause a decrease in plasma VWF levels in VWD, and the goal of this study was to elucidate the pathogenic origins of VWD for a group of mutations in the VWF D'D3 region traditionally associated with type 1 VWD. Varying ratios of mutant-to-wild-type VWF were expressed in two cell lines in order to study the intracellular location, multimer assembly, secretion and function of VWF.

Characterization of collagen thin films for von Willebrand factor binding and platelet adhesion.

Von Willebrand factor (VWF) binding and platelet adhesion to subendothelial collagens are initial events in thrombus formation at sites of vascular injury. These events are often studied in vitro using flow assays designed to mimic vascular hemodynamics. Flow assays commonly employ collagen-functionalized substrates, but a lack of standardized methods of surface ligation limits their widespread use as a clinical diagnostic.