title: Response to desmopressin is influenced by the genotype and phenotype in type 1 von Willebrand disease (VWD): results from the European Study MCMDM-1VWD.
abstract: We have prospectively evaluated the biologic response to desmopressin in 77 patients with type 1 von Willebrand disease (VWD) enrolled within the Molecular and Clinical Markers for the Diagnosis and Management of type 1 VWD project. Complete response to desmopressin was defined as an increase of both ristocetin cofactor activity (VWF:RCo) and factor VIII coagulant activity (FVIII:C) to 50 IU/dL or higher and partial response as VWF:RCo or FVIII:C lower than 50 IU/dL after infusion, but at least 3-fold the basal level. Complete response was observed in 83% of patients; partial in 13%; and no response in 4%. Patients with some abnormality of VWF multimeric pattern had significantly lower basal FVIII:C and VWF, lower VWF:RCo/Ag ratio, and less complete responses to desmopressin than patients with a normal multimeric pattern (P=.002). Patients with mutations at codons 1130 and 1205 in the D'-D3 domain had the greatest relative increase, but shortest FVIII and VWF half-lives after infusion. Most partial and nonresponsive patients had mutations in the A1-A3 domains. Response to desmopressin in these VWD patients seemed to be associated with the location of the causative mutation. The presence of subtle multimeric abnormalities did not hamper potential clinically useful responses, as in typical type 1 VWD.
authors.affiliation: Department of Hematology, San Bortolo Hospital, Vicenza, Italy. castaman@hemato.ven.it
authors.forename: Giancarlo
authors.initials: G
authors.lastname: Castaman
authors.forename: Stefan
authors.initials: S
authors.lastname: Lethagen
authors.forename: Augusto B
authors.initials: AB
authors.lastname: Federici
authors.forename: Alberto
authors.initials: A
authors.lastname: Tosetto
authors.forename: Anne
authors.initials: A
authors.lastname: Goodeve
authors.forename: Ulrich
authors.initials: U
authors.lastname: Budde
authors.forename: Javier
authors.initials: J
authors.lastname: Batlle
authors.forename: Dominique
authors.initials: D
authors.lastname: Meyer
authors.forename: Claudine
authors.initials: C
authors.lastname: Mazurier
authors.forename: Edith
authors.initials: E
authors.lastname: Fressinaud
authors.forename: Jenny
authors.initials: J
authors.lastname: Goudemand
authors.forename: Jeroen
authors.initials: J
authors.lastname: Eikenboom
authors.forename: Reinhard
authors.initials: R
authors.lastname: Schneppenheim
authors.forename: Jorgen
authors.initials: J
authors.lastname: Ingerslev
authors.forename: Zdena
authors.initials: Z
authors.lastname: Vorlova
authors.forename: David
authors.initials: D
authors.lastname: Habart
authors.forename: Lars
authors.initials: L
authors.lastname: Holmberg
authors.forename: John
authors.initials: J
authors.lastname: Pasi
authors.forename: Frank
authors.initials: F
authors.lastname: Hill
authors.forename: Ian
authors.initials: I
authors.lastname: Peake
authors.forename: Francesco
authors.initials: F
authors.lastname: Rodeghiero
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D001780:Blood Coagulation Tests / Q000379:methods; D002648:Child; D003894:Deamino Arginine Vasopressin / Q000008:administration & dosage*; D005169:Factor VIII / Q000032:analysis / Q000737:chemistry; D005260:Female; D005838:Genotype; D006490:Hemostatics / Q000008:administration & dosage*; D006801:Humans; D008297:Male; D008875:Middle Aged; D009154:Mutation; D011446:Prospective Studies; D011486:Protein C / Q000032:analysis / Q000737:chemistry; D017434:Protein Structure, Tertiary / Q000235:genetics; D012310:Ristocetin / Q000737:chemistry; D014842:von Willebrand Diseases / Q000188:drug therapy* / Q000235:genetics*
chemical_list: D006490:Hemostatics; D011486:Protein C; D012310:Ristocetin; C078147:F8 protein, human; D005169:Factor VIII; D003894:Deamino Arginine Vasopressin