Intracellular cotrafficking of factor VIII and von Willebrand factor type 2N variants to storage organelles.

THROMBOSIS AND HEMOSTASIS Intracellular cotrafficking of factor VIII and von Willebrand factor type 2N variants to storage organelles

Weibel-Palade bodies (WPBs) are the endothelial storage organelles that are formed upon von Willebrand factor (VWF) expression. Apart from VWF, WPBs contain a variety of hemostatic and inflammatory proteins. Some of these are thought to be targeted to WPBs by directly interacting with VWF in the secretory pathway. Previous studies have demonstrated that coexpression of factor VIII (FVIII) with ...

Intracellular co-trafficking of factor VIII and von Willebrand factor type 2N variants to storage organelles Running head: FVIII and VWF type 2N co-trafficking

Storage of Factor VIII Variants with Impaired von Willebrand Factor Binding in Weibel-Palade Bodies in Endothelial Cells

BACKGROUND Point mutations resulting in reduced factor VIII (FVIII) binding to von Willebrand factor (VWF) are an important cause of mild/moderate hemophilia A. Treatment includes desmopressin infusion, which concomitantly increases VWF and FVIII plasma levels, apparently from storage pools containing both proteins. The source of these VWF/FVIII co-storage pools and the mechanism of granule bio...

Von Willebrand disease

There are three major types of VWD disease. Type 1, the most frequent form, is characterized by a partial quantitative deficiency in von Willebrand factor (VWF). Type 2 is a qualitative deficiency, and Type 3 is a virtually complete deficiency. Type 2 VWD is divided into four subtypes. Type 2A includes variants with decreased platelet adhesion caused by a selective deficiency in high-molecular ...

Von Willebrand disease

There are three major types of VWD disease. Type 1, the most frequent form, is characterized by a partial quantitative deficiency in von Willebrand factor (VWF). Type 2 is a qualitative deficiency, and Type 3 is a virtually complete deficiency. Type 2 VWD is divided into four subtypes. Type 2A includes variants with decreased platelet adhesion caused by a selective deficiency in high-molecular ...