title: Unique interactions of asialo von Willebrand factor with platelets in platelet-type von Willebrand disease.
abstract: The present studies demonstrate that platelets from patients with platelet-type von Willebrand disease show specific and saturable binding of asialo von Willebrand factor (AS-vWF) under conditions where such binding is not observed with normal platelets. Although specific binding of 125I-AS-vWF to formalin-fixed normal platelets could not be demonstrated, specific binding to fixed patient platelets was seen with an apparent Kd of 1.3 micrograms/mL and specific maximally bound ligand of 0.40 micrograms/10(8) platelets. Preincubation of patient platelets with the antiglycoprotein Ib (anti-GPIb) monoclonal antibody AS-2 reduced total binding close to the level of computer-estimated nonspecific binding. In contrast, binding was not reduced by preincubation with anti-GPIIb/IIIa monoclonal antibody or with 5 mmol/L EDTA. Under stirring conditions, the binding of AS-vWF to fixed patient platelets was accompanied by a strong agglutination response. AS-vWF-induced agglutination was similarly observed in patient but not normal platelet-rich plasma (PRP) in the presence of 5 mmol/L EDTA. In the absence of EDTA, AS-vWF produced a full aggregation response in patient PRP at concentrations as low as 0.1 microgram/mL in contrast to the 2 to 20 micrograms/mL required by normal PRP. Both thromboxane B2 formation and adenosine triphosphate secretion showed an AS-vWF concentration dependence paralleling the aggregation responses. These studies show that a major difference in the platelets from patients with platelet-type von Willebrand disease is the presence of an exposed, high-affinity binding site associated with GPIb that recognizes AS-vWF.
mesh_terms: D000255:Adenosine Triphosphate / Q000378:metabolism; D001212:Asialoglycoproteins / Q000502:physiology*; D001665:Binding Sites; D001792:Blood Platelets / Q000502:physiology*; D004492:Edetic Acid / Q000494:pharmacology; D006801:Humans; D010974:Platelet Aggregation; D012310:Ristocetin / Q000494:pharmacology; D013929:Thromboxane B2 / Q000096:biosynthesis; D014842:von Willebrand Diseases / Q000503:physiopathology*; D014841:von Willebrand Factor / Q000502:physiology*
chemical_list: D001212:Asialoglycoproteins; D014841:von Willebrand Factor; D012310:Ristocetin; D013929:Thromboxane B2; D000255:Adenosine Triphosphate; D004492:Edetic Acid