Subcellular membrane and granule fractions derived from human platelets contain factor VIIII antigen and von Willebrand factor activity but not factor VII procoagulant activity. Circulating platelets constitute a significant reservoir of plasma factor VIII antigen, containing approximately 15% of the amount of factor VIII antigen present in platelet-poor plasma. The antibiotic ristocetin, which...

5006 The Journal of Clinical Investigation http://www.jci.org Volume 123 Number 12 December 2013 1998;91(12):4397–4418. 5. Ruggeri ZM, Pareti FI, Mannucci PM, Ciavarella N, Zimmerman TS. Heightened interaction between platelets and Factor VIII/von Willebrand factor in a new subtype of von Willebrand’s disease. N Engl J Med. 1980;302(19):1047–1051. 6. Ware J, et al. Identification of a point mut...

Two monoclonal antibodies-one that blocks ristocetininduced platelet binding of von Willebrand factor to glycoprotein lb and one that blocks adenosine diphosphateinduced binding of fibrinogen to the glycoprotein llb/Illa complex-were used to assess the binding site(s) for von Willebrand factor when platelets are stimulated with thrombin or adenosine diphosphate (ADP). Neither agonist induced bi...

Variant von Willebrand disease designated as type I New York or type Malmo is characterized by enhanced ristocetin-induced platelet agglutination with normal von Willebrand factor multimeric distribution in plasma. We have studied four such patients belonging to three unrelated families and found in all of them a unique cytosine-to-thymine transition changing the codon for Pro" (CCG) to Leu (CI...

Pseudo (platelet-type)-von Willebrand disease is an autosomal dominant bleeding disorder caused by the hyperfunction of a receptor on the platelet surface. The abnormal receptor, glycoprotein Ib, displays increased affinity for its ligand, von Willebrand factor. Four members (normal mother/affected father/two affected daughters) of a family with pseudo-von Willebrand disease were studied to det...

Cultured human endothelial cells synthesize and secrete a protein(s) which has Factor VIII antigen but which lacks Factor VIII clot-promoting activity (J. Clin. Invest. 52, 2757-2764, 1973). Von Willebrand factor activity has been identified in medium from cultured human endothelial cells. This activity was demonstrated by the ability to correct the defect in platelet adhesiveness of blood obta...

BACKGROUND Nucleotide variations not changing protein sequences are considered silent mutations; accumulating data suggest that they can, however, be important in human diseases. DESIGN AND METHODS We report an altered splicing process induced by a silent substitution (c.7056C>T) in the von Willebrand factor gene in a case of type 1 von Willebrand disease originally classified as lacking von ...

A form of von Willebrand’s disease has been described with enhanced ristocetin-induced platelet aggregation and anodal migration of the factor VIll/von Willebrand factor protein (type lIb). We studied two families with this form of von Willebrand s disease and macrothrombocytopenia. We have found that these platelets bind more of the normal and intermediate-sized multimers of the factor VIll/vo...

The early response to coronary artery injury was investigated in normal swine and in swine with von Willebrand disease (vWD). Thirty minutes after coronary endothelial denudation, a monolayer of platelets was adherent to areas of simple injury in both bleeder and normal swine. The number of adherent platelets was not significantly different in the two phenotypes. Injury involving the media of t...

Heparinized porcine blood and plasma, at constant hydrostatic pressure, was allowed to flow through a 5-mm incision in a small piece of porcine skin. Changes in the exuded blood volume were measured, and the incision site was examined microscopically. When normal blood flowed through either normal or von Willebrand skin, the exuded blood volume decreased gradually and eventually stopped. Micros...