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- W2590624566 abstract "Abstract Introduction: Von Willebrand Disease (VWD) Type 2B is characterized by increased affinity of VWF for the platelet glycoprotein receptor Ib (GPIb). Consequently, infusion of desmopressin, a standard of treatment for other forms of VWD, causes transient thrombocytopenia in patients with VWD-2B. The aim of the study was to test whether the novel anti-VWF aptamer ARC1779, which inhibits the interaction of VWF with GPIb, could abrogate the transient desmopressin-induced thrombocytopenia in VWD-2B. Patients and Methods: This was part of a clinical trial using a double-blind, randomized, placebo-controlled, crossover design. A patient with VWD 2B received desmopressin (0.4 mcg/kg) alone, or desmopressin after pre-treatment with ARC1779 targeted to a plasma concentration of 10 mcg/mL. Multiple blood samples were obtained over 24 hours to measure von Willebrand Factor Antigen, Ristocetin Cofactor (RiCO), FVIII activity and multimers. Results: Desmopressin alone (open circles) increased VWF:Ag by 38% (not shown), and VWF:RiCo 3.4-fold within 30 min, and profoundly decreased platelet counts by 87%. In striking contrast, ARC1779 (solid triangles) completely prevented the desmopressin induced fall in platelet counts (Figure), although the increase in vWF:Ag and vWF:RiCO was greater (2.7-fold and 12-fold, respectively). Conclusions: This randomized, double-blind, placebo-controlled experiment shows that ARC1779 effectively prevents consumption of VWF and platelets in response to desmopressin in VWD Type 2B. It provides in vivo proof of concept that ARC1779 is a potent inhibitor of the VWF A1 domain interaction with GPIb. Figure Figure" @default.
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- W2590624566 date "2008-11-16" @default.
- W2590624566 modified "2023-10-01" @default.
- W2590624566 title "The Anti Von Willebrand Factor Aptamer ARC1779 Prevents the Desmopressin-Induced Thrombocytopenia in VWD Type 2B." @default.
- W2590624566 doi "https://doi.org/10.1182/blood.v112.11.3374.3374" @default.
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