ristocetin assay

Ristocetin is an antibiotic that induces vWF to bind to platelet glycoprotein Ib (GPIb) receptors, causing platelet agglutination in vitro. The ristocetin cofactor assay quantifies functional vWF activity by measuring the degree of agglutination of normal platelets when patient plasma (containing vWF) is mixed with ristocetin. Reduced ristocetin cofactor activity indicates either quantitative (Type 1, Type 3) or qualitative (Type 2) defects in vWF, characteristic of von Willebrand disease—the most common inherited bleeding disorder. In Bernard-Soulier syndrome, a disorder of the platelet GPIb receptor itself, ristocetin-induced platelet aggregation (RIPA) is also reduced or absent despite normal vWF levels, but mixing studies with normal plasma fail to correct the defect (unlike in vWD, where added normal vWF corrects aggregation). Conversely, in Type 2B vWD, there is a gain-of-function mutation causing increased affinity of vWF for GPIb, leading to enhanced aggregation at low-dose ristocetin. Clinically, the assay helps differentiate: (1) vWD subtypes, (2) Bernard-Soulier syndrome, and (3) platelet-type (pseudo-) vWD, which also shows enhanced RIPA due to a platelet-sided defect. Typically assessed alongside vWF antigen level, Factor VIII activity, and vWF multimer analysis to fully characterize the bleeding disorder. Patients present with mucocutaneous bleeding, easy bruising, epistaxis, or menorrhagia; management may include desmopressin (DDAVP) for mild Type 1 vWD or vWF-containing factor concentrates for severe types.