title: The agglutination of human platelets by botrocetin: evidence that botrocetin and ristocetin act at different sites on the factor VIII molecule and platelet membrane.
abstract: Botrocetin caused a factor VIII (FVIII) dependent platelet agglutination which was associated with a reduction in the plasma levels of all FVIII parameters as a result of specific binding of FVIII to the platelets. The site of binding of FVIII to the platelet in response to ristocetin or botrocetin involves the glycoprotein I complex. This is suggested by the inability of chymotrypsin treated platelets or platelets from patients with the Bernard-Soulier syndrome to agglutinate in response to ristocetin. These platelets responded to botrocetin , but this was greatly reduced compared to normal. Crossed immunoelectrophoretic analysis indicated that in the presence of botrocetin most multimetric forms of FVIII bound to the platelet, whereas ristocetin caused binding of high and intermediate molecular weight forms. The antibiotic vancomycin inhibited platelet agglutination by ristocetin but had no effect on that caused by botrocetin . Assays of FVIII von Willebrand factor (VIII:vWf) using botrocetin compared well with those obtained using ristocetin in plasmas from normal individuals and from patients with classical von Willebrand disease (vWd). However, a patient with variant vWd demonstrated 100% botrocetin cofactor activity and 0% ristocetin cofactor activity. This suggested that the site of interaction on the FVIII molecule for botrocetin and ristocetin are different. Therefore the diagnosis of some von Willebrand variants cannot be excluded on the basis of a normal botrocetin cofactor assay.
mesh_terms: D001792:Blood Platelets / Q000187:drug effects* / Q000378:metabolism; D002462:Cell Membrane / Q000187:drug effects; D003435:Crotalid Venoms / Q000378:metabolism / Q000494:pharmacology*; D005169:Factor VIII / Q000032:analysis / Q000378:metabolism*; D006801:Humans; D007123:Immunoelectrophoresis, Two-Dimensional; D010974:Platelet Aggregation / Q000187:drug effects*; D012310:Ristocetin / Q000494:pharmacology*
chemical_list: D003435:Crotalid Venoms; D012310:Ristocetin; C030961:botrocetin; D005169:Factor VIII